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203 results on '"Raes, Jeroen"'

1. Fat and not sugar as the determining factor for gut microbiota changes, obesity and related metabolic disorders in mice

Author: UCL - SSS/LDRI - Louvain Drug Research Institute, Suriano, Francesco, Vieira-Silva, Sara, Falony, Gwen, de Wouters d'Oplinter, Alice, Paone, Paola, Delzenne, Nathalie M., Everard, Amandine, Raes, Jeroen, Van Hul, Matthias, Cani, Patrice D., UCL - SSS/LDRI - Louvain Drug Research Institute, Suriano, Francesco, Vieira-Silva, Sara, Falony, Gwen, de Wouters d'Oplinter, Alice, Paone, Paola, Delzenne, Nathalie M., Everard, Amandine, Raes, Jeroen, Van Hul, Matthias, and Cani, Patrice D.
Abstract: Diet-induced obesity contributes to the development of type 2 diabetes, insulin resistance, metabolic inflammation, oxidative and endoplasmic reticulum (ER) stress. Overall, obesity is associated with deviations in the composition and functionality of the gut microbiota. There are many divergent findings regarding the link between the excessive intake of certain dietary components (i.e., fat and sugar) and obesity development. We therefore investigated the effect of specific diets, with a different content in sugar and fat, in promoting obesity and related comorbidities as well as their impact on microbial load and gut microbiota composition/diversity.C57BL/6J mice were fed either a low-sugar, low-fat control diet (CT), a high-sugar diet (HS), a high-fat, high-sugar diet (HF/HS), or a high-fat diet (HF) for 8 weeks. The impact of the different diets on obesity, glucose metabolism, inflammation, and oxidative and ER stress were determined. Diet-induced changes in the gut microbiota composition and density were also analyzed.HF diet-fed mice showed the highest body weight and fat mass gains and displayed the most impaired glucose and insulin profiles. HS, HF/HS, and HF diets differently affected hepatic cholesterol content and mRNA expression of several markers associated with immune cells, inflammation, oxidative and ER stress in several organs/tissues. Additionally, HF diet feeding resulted in a decreased microbial load at the end of the experiment. When analyzing the gut microbiota composition, we found that HS, HF/HS, and HF diets induced specific changes in the abundance of certain bacterial taxa. Taken together, our results highlight that dietary intake of different macronutrients distinctively impacts the development of an obese/diabetic state and the regulation of metabolic inflammation in specific organs. We propose that these differences are not only obesity-driven but that changes in the gut microbiota composition may play a key role in this context.
Published: 2023

2. Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential

Author: Afd Pharmacology, Pharmacology, Krukowski, Hubert, Valkenburg, Sophie, Madella, Avra Melina, Garssen, Johan, van Bergenhenegouwen, Jeroen, Overbeek, Saskia Adriana, Huys, Geert R.B., Raes, Jeroen, Glorieux, Griet, Afd Pharmacology, Pharmacology, Krukowski, Hubert, Valkenburg, Sophie, Madella, Avra Melina, Garssen, Johan, van Bergenhenegouwen, Jeroen, Overbeek, Saskia Adriana, Huys, Geert R.B., Raes, Jeroen, and Glorieux, Griet
Published: 2023

3. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author: Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Alili, Rohia, Galijatovic, Ehm Astrid Andersson, Barthelemy, Olivier, Bastard, Jean Philippe, Batisse, Jean Paul, Bel-Lassen, Pierre, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Ciangura, Cecile, Collet, Jean Philippe, Dietrich, Arne, Djebbar, Morad, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Pons, Nicolas, Graine, Marianne, Grünemann, Caroline, Hartemann, Agnes, Hartmann, Bolette, Hornbak, Malene, Jaqueminet, Sophie, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Kammer, Judith, Karup, Nikolaj, Kozlowski, Ruby, Kuhn, Michael, Lejard, Véronique, Letunic, Ivica, Levenez, Florence, Marko, Lajos, Martinez-Gili, Laura, Massey, Robin, Maziers, Nicolas, Moitinho-Silva, Lucas, Montalescot, Gilles, Neves, Ana Luisa, Le Pavin, Laetitia Pasero, Pousset, Francoise, Rodriguez-Martinez, Andrea, Schmidt, Sebastien, Schütz, Tatjana, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D., Vanduyvenboden, Thierry, Verger, Eric O., Walther, Stefanie, Zucker, Jean Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, Dumas, Marc Emmanuel, Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Alili, Rohia, Galijatovic, Ehm Astrid Andersson, Barthelemy, Olivier, Bastard, Jean Philippe, Batisse, Jean Paul, Bel-Lassen, Pierre, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Ciangura, Cecile, Collet, Jean Philippe, Dietrich, Arne, Djebbar, Morad, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Pons, Nicolas, Graine, Marianne, Grünemann, Caroline, Hartemann, Agnes, Hartmann, Bolette, Hornbak, Malene, Jaqueminet, Sophie, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Kammer, Judith, Karup, Nikolaj, Kozlowski, Ruby, Kuhn, Michael, Lejard, Véronique, Letunic, Ivica, Levenez, Florence, Marko, Lajos, Martinez-Gili, Laura, Massey, Robin, Maziers, Nicolas, Moitinho-Silva, Lucas, Montalescot, Gilles, Neves, Ana Luisa, Le Pavin, Laetitia Pasero, Pousset, Francoise, Rodriguez-Martinez, Andrea, Schmidt, Sebastien, Schütz, Tatjana, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D., Vanduyvenboden, Thierry, Verger, Eric O., Walther, Stefanie, Zucker, Jean Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, and Dumas, Marc Emmanuel
Abstract: The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
Published: 2023

4. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

Author: Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, Pedersen, Oluf, Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf
Abstract: Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis., Funding agencies:Marie Sklodowska-Curie Individual Fellowship 797267Odense University Hospital Research Fund R15-A800
Published: 2023
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5. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies

Author: Kennedy, Katherine M., de Goffau, Marcus C., Perez-Muñoz, Maria Elisa, Arrieta, Marie Claire, Bäckhed, Fredrik, Bork, Peer, Braun, Thorsten, Bushman, Frederic D., Dore, Joel, de Vos, Willem M., Earl, Ashlee M., Eisen, Jonathan A., Elovitz, Michal A., Ganal-Vonarburg, Stephanie C., Gänzle, Michael G., Garrett, Wendy S., Hall, Lindsay J., Hornef, Mathias W., Huttenhower, Curtis, Konnikova, Liza, Lebeer, Sarah, Macpherson, Andrew J., Massey, Ruth C., McHardy, Alice Carolyn, Koren, Omry, Lawley, Trevor D., Ley, Ruth E., O’Mahony, Liam, O’Toole, Paul W., Pamer, Eric G., Parkhill, Julian, Raes, Jeroen, Rattei, Thomas, Salonen, Anne, Segal, Eran, Segata, Nicola, Shanahan, Fergus, Sloboda, Deborah M., Smith, Gordon C.S., Sokol, Harry, Spector, Tim D., Surette, Michael G., Tannock, Gerald W., Walker, Alan W., Yassour, Moran, Walter, Jens, Kennedy, Katherine M., de Goffau, Marcus C., Perez-Muñoz, Maria Elisa, Arrieta, Marie Claire, Bäckhed, Fredrik, Bork, Peer, Braun, Thorsten, Bushman, Frederic D., Dore, Joel, de Vos, Willem M., Earl, Ashlee M., Eisen, Jonathan A., Elovitz, Michal A., Ganal-Vonarburg, Stephanie C., Gänzle, Michael G., Garrett, Wendy S., Hall, Lindsay J., Hornef, Mathias W., Huttenhower, Curtis, Konnikova, Liza, Lebeer, Sarah, Macpherson, Andrew J., Massey, Ruth C., McHardy, Alice Carolyn, Koren, Omry, Lawley, Trevor D., Ley, Ruth E., O’Mahony, Liam, O’Toole, Paul W., Pamer, Eric G., Parkhill, Julian, Raes, Jeroen, Rattei, Thomas, Salonen, Anne, Segal, Eran, Segata, Nicola, Shanahan, Fergus, Sloboda, Deborah M., Smith, Gordon C.S., Sokol, Harry, Spector, Tim D., Surette, Michael G., Tannock, Gerald W., Walker, Alan W., Yassour, Moran, and Walter, Jens
Abstract: Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
Published: 2023

6. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

Author: Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, Pedersen, Oluf, Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf
Abstract: Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral–bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our ‘omics’ and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.
Published: 2023

7. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies

Author: Kennedy, Katherine M., de Goffau, Marcus C., Perez-Muñoz, Maria Elisa, Arrieta, Marie Claire, Bäckhed, Fredrik, Bork, Peer, Braun, Thorsten, Bushman, Frederic D., Dore, Joel, de Vos, Willem M., Earl, Ashlee M., Eisen, Jonathan A., Elovitz, Michal A., Ganal-Vonarburg, Stephanie C., Gänzle, Michael G., Garrett, Wendy S., Hall, Lindsay J., Hornef, Mathias W., Huttenhower, Curtis, Konnikova, Liza, Lebeer, Sarah, Macpherson, Andrew J., Massey, Ruth C., McHardy, Alice Carolyn, Koren, Omry, Lawley, Trevor D., Ley, Ruth E., O’Mahony, Liam, O’Toole, Paul W., Pamer, Eric G., Parkhill, Julian, Raes, Jeroen, Rattei, Thomas, Salonen, Anne, Segal, Eran, Segata, Nicola, Shanahan, Fergus, Sloboda, Deborah M., Smith, Gordon C.S., Sokol, Harry, Spector, Tim D., Surette, Michael G., Tannock, Gerald W., Walker, Alan W., Yassour, Moran, Walter, Jens, Kennedy, Katherine M., de Goffau, Marcus C., Perez-Muñoz, Maria Elisa, Arrieta, Marie Claire, Bäckhed, Fredrik, Bork, Peer, Braun, Thorsten, Bushman, Frederic D., Dore, Joel, de Vos, Willem M., Earl, Ashlee M., Eisen, Jonathan A., Elovitz, Michal A., Ganal-Vonarburg, Stephanie C., Gänzle, Michael G., Garrett, Wendy S., Hall, Lindsay J., Hornef, Mathias W., Huttenhower, Curtis, Konnikova, Liza, Lebeer, Sarah, Macpherson, Andrew J., Massey, Ruth C., McHardy, Alice Carolyn, Koren, Omry, Lawley, Trevor D., Ley, Ruth E., O’Mahony, Liam, O’Toole, Paul W., Pamer, Eric G., Parkhill, Julian, Raes, Jeroen, Rattei, Thomas, Salonen, Anne, Segal, Eran, Segata, Nicola, Shanahan, Fergus, Sloboda, Deborah M., Smith, Gordon C.S., Sokol, Harry, Spector, Tim D., Surette, Michael G., Tannock, Gerald W., Walker, Alan W., Yassour, Moran, and Walter, Jens
Abstract: Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
Published: 2023

8. The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice

Author: Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, Pedersen, Oluf, Fan, Yong, Støving, René Klinkby, Berreira Ibraim, Samar, Hyötyläinen, Tuulia, Thirion, Florence, Arora, Tulika, Lyu, Liwei, Stankevic, Evelina, Hansen, Tue Haldor, Déchelotte, Pierre, Sinioja, Tim, Ragnarsdottir, Oddny, Pons, Nicolas, Galleron, Nathalie, Quinquis, Benoît, Levenez, Florence, Roume, Hugo, Falony, Gwen, Vieira-Silva, Sara, Raes, Jeroen, Clausen, Loa, Telléus, Gry Kjaersdam, Bäckhed, Fredrik, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf
Abstract: Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral–bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our ‘omics’ and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis.
Published: 2023

9. Advancing human gut microbiota research by considering gut transit time

Author: Procházková, Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, Roager, Henrik Munch, Procházková, Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, and Roager, Henrik Munch
Abstract: Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet–microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.
Published: 2023

10. Advancing human gut microbiota research by considering gut transit time

Author: Procházková , Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, Roager, Henrik M., Procházková , Nicola, Falony, Gwen, Dragsted, Lars Ove, Licht, Tine Rask, Raes, Jeroen, and Roager, Henrik M.
Abstract: Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet–microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.
Published: 2023

11. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

Author: Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Alili, Rohia, Galijatovic, Ehm Astrid Andersson, Barthelemy, Olivier, Bastard, Jean Philippe, Batisse, Jean Paul, Bel-Lassen, Pierre, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Ciangura, Cecile, Collet, Jean Philippe, Dietrich, Arne, Djebbar, Morad, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Pons, Nicolas, Graine, Marianne, Grünemann, Caroline, Hartemann, Agnes, Hartmann, Bolette, Hornbak, Malene, Jaqueminet, Sophie, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Kammer, Judith, Karup, Nikolaj, Kozlowski, Ruby, Kuhn, Michael, Lejard, Véronique, Letunic, Ivica, Levenez, Florence, Marko, Lajos, Martinez-Gili, Laura, Massey, Robin, Maziers, Nicolas, Moitinho-Silva, Lucas, Montalescot, Gilles, Neves, Ana Luisa, Le Pavin, Laetitia Pasero, Pousset, Francoise, Rodriguez-Martinez, Andrea, Schmidt, Sebastien, Schütz, Tatjana, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D., Vanduyvenboden, Thierry, Verger, Eric O., Walther, Stefanie, Zucker, Jean Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, Dumas, Marc Emmanuel, Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Alili, Rohia, Galijatovic, Ehm Astrid Andersson, Barthelemy, Olivier, Bastard, Jean Philippe, Batisse, Jean Paul, Bel-Lassen, Pierre, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Ciangura, Cecile, Collet, Jean Philippe, Dietrich, Arne, Djebbar, Morad, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Pons, Nicolas, Graine, Marianne, Grünemann, Caroline, Hartemann, Agnes, Hartmann, Bolette, Hornbak, Malene, Jaqueminet, Sophie, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Kammer, Judith, Karup, Nikolaj, Kozlowski, Ruby, Kuhn, Michael, Lejard, Véronique, Letunic, Ivica, Levenez, Florence, Marko, Lajos, Martinez-Gili, Laura, Massey, Robin, Maziers, Nicolas, Moitinho-Silva, Lucas, Montalescot, Gilles, Neves, Ana Luisa, Le Pavin, Laetitia Pasero, Pousset, Francoise, Rodriguez-Martinez, Andrea, Schmidt, Sebastien, Schütz, Tatjana, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D., Vanduyvenboden, Thierry, Verger, Eric O., Walther, Stefanie, Zucker, Jean Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, and Dumas, Marc Emmanuel
Abstract: The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
Published: 2023

12. Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice

Author: UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service d'endocrinologie et de nutrition, Le Roy, Tiphaine, Moens De Hase, Emilie, Van Hul, Matthias, Paquot, Adrien, Pelicaen, Rudy, Régnier, Marion, Depommier, Clara, Druart, Céline, Everard, Amandine, Maiter, Dominique, Delzenne, Nathalie M., Bindels, Laure B., de Barsy, Marie, Loumaye, Audrey, Hermans, Michel, Thissen, Jean-Paul, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, Muccioli, Giulio, Cani, Patrice D., UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service d'endocrinologie et de nutrition, Le Roy, Tiphaine, Moens De Hase, Emilie, Van Hul, Matthias, Paquot, Adrien, Pelicaen, Rudy, Régnier, Marion, Depommier, Clara, Druart, Céline, Everard, Amandine, Maiter, Dominique, Delzenne, Nathalie M., Bindels, Laure B., de Barsy, Marie, Loumaye, Audrey, Hermans, Michel, Thissen, Jean-Paul, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, Muccioli, Giulio, and Cani, Patrice D.
Abstract: Objective: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115T, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice. Design: We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115T on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice. Results: This newly identified bacterium was detected in 62.7%-69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115T, but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115T administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition. Conclusions: These results suggest that D. welbionis J115T directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.
Published: 2022

13. Bidirectional Interactions between Arboviruses and the Bacterial and Viral Microbiota in Aedes aegypti and Culex quinquefasciatus

Author: Shi, Chenyan, Beller, Leen, Wang, Lanjiao, Rosales Rosas, Ana, De Coninck, Lander, Héry, Lyza, Mousson, Laurence, Pagès, Nonito, Raes, Jeroen, Delang, Leen, Vega-Rúa, Anubis, Failloux, Anna-Bella, Matthijnssens, Jelle, Shi, Chenyan, Beller, Leen, Wang, Lanjiao, Rosales Rosas, Ana, De Coninck, Lander, Héry, Lyza, Mousson, Laurence, Pagès, Nonito, Raes, Jeroen, Delang, Leen, Vega-Rúa, Anubis, Failloux, Anna-Bella, and Matthijnssens, Jelle
Abstract: Mosquitoes are important vectors for many arboviruses. It is becoming increasingly clear that various symbiotic microorganisms (including bacteria and insect-specific viruses; ISVs) in mosquitoes have the potential to modulate the ability of mosquitoes to transmit arboviruses. In this study, we compared the bacteriome and virome (both eukaryotic viruses and bacteriophages) of female adult Aedes aegypti and Culex quinquefasciatus mosquitoes fed with sucrose/water, blood, or blood spiked with Zika virus (ZIKV) or West Nile virus (WNV), respectively. Furthermore, we investigated associations between the microbiota and vector competence. We show that the influence of arboviruses on the mosquito microbiome—and vice versa—is distinct for each combination of arbovirus/mosquito species. The presence of ZIKV resulted in a temporarily increased Aedes ISV diversity. However, this effect was distinct for different ISVs: some ISVs decreased following the blood meal (Aedes aegypti totivirus), whereas other ISVs increased only when the blood contained ZIKV (Guadeloupe mosquito virus). Also, the diversity of the Aedes bacteriome depended on the diet and the presence of ZIKV, with a lower diversity observed for mosquitoes receiving blood without ZIKV. In Cx. quinquefasciatus, some ISVs increased in WNV-infected mosquitoes (Guadeloupe Culex tymo-like virus). Particularly, the presence of Wenzhou sobemo-like virus 3 (WSLV3) was associated with the absence of infectious WNV in mosquito heads, suggesting that WSLV3 might affect vector competence for WNV. Distinct profiles of bacteriophages were identified in Culex mosquitoes depending on diet, despite the lack of clear changes in the bacteriome. Overall, our data demonstrate a complex three-way interaction among arboviruses, resident microbiota, and the host, which is distinct for different arbovirus–mosquito combinations. A better understanding of these interactions may lead to the identification of microbiota able to suppress the abil
Published: 2022

14. Functional repertoire convergence of distantly related eukaryotic plankton lineages abundant in the sunlit ocean

Author: Delmont, Tom O., Gaia, Morgan, Hinsinger, Damien D., Frémont, Paul, Vanni, Chiara, Fernandez-Guerra, Antonio, Eren, A. Murat, Kourlaiev, Artem, d'Agata, Leo, Clayssen, Quentin, Villar, Emilie, Labadie, Karine, Cruaud, Corinne, Poulain, Julie, Da Silva, Corinne, Wessner, Marc, Noel, Benjamin, Aury, Jean-Marc, Sunagawa, Shinichi, Acinas, Silvia G., Bork, Peer, Karsenti, Eric, Bowler, Chris, Sardet, Christian, Stemmann, Lars, de Vargas, Colomban, Wincker, Patrick, Lescot, Magali, Babin, Marcel, Gorsky, Gabriel, Grimsley, Nigel, Guidi, Lionel, Hingamp, Pascal, Jaillon, Olivier, Kandels, Stefanie, Iudicone, Daniele, Ogata, Hiroyuki, Pesant, Stéphane, Sullivan, Matthew B., Not, Fabrice, Lee, Karp Boss, Boss, Emmanuel, Cochrane, Guy, Follows, Michael, Poulton, Nicole, Raes, Jeroen, Sieracki, Mike, Speich, Sabrina, Pelletier, Eric, Delmont, Tom O., Gaia, Morgan, Hinsinger, Damien D., Frémont, Paul, Vanni, Chiara, Fernandez-Guerra, Antonio, Eren, A. Murat, Kourlaiev, Artem, d'Agata, Leo, Clayssen, Quentin, Villar, Emilie, Labadie, Karine, Cruaud, Corinne, Poulain, Julie, Da Silva, Corinne, Wessner, Marc, Noel, Benjamin, Aury, Jean-Marc, Sunagawa, Shinichi, Acinas, Silvia G., Bork, Peer, Karsenti, Eric, Bowler, Chris, Sardet, Christian, Stemmann, Lars, de Vargas, Colomban, Wincker, Patrick, Lescot, Magali, Babin, Marcel, Gorsky, Gabriel, Grimsley, Nigel, Guidi, Lionel, Hingamp, Pascal, Jaillon, Olivier, Kandels, Stefanie, Iudicone, Daniele, Ogata, Hiroyuki, Pesant, Stéphane, Sullivan, Matthew B., Not, Fabrice, Lee, Karp Boss, Boss, Emmanuel, Cochrane, Guy, Follows, Michael, Poulton, Nicole, Raes, Jeroen, Sieracki, Mike, Speich, Sabrina, and Pelletier, Eric
Abstract: Marine planktonic eukaryotes play critical roles in global biogeochemical cycles and climate. However, their poor representation in culture collections limits our understanding of the evolutionary history and genomic underpinnings of planktonic ecosystems. Here, we used 280 billion Tara Oceans metagenomic reads from polar, temperate, and tropical sunlit oceans to reconstruct and manually curate more than 700 abundant and widespread eukaryotic environmental genomes ranging from 10 Mbp to 1.3 Gbp. This genomic resource covers a wide range of poorly characterized eukaryotic lineages that complement long-standing contributions from culture collections while better representing plankton in the upper layer of the oceans. We performed the first, to our knowledge, comprehensive genome-wide functional classification of abundant unicellular eukaryotic plankton, revealing four major groups connecting distantly related lineages. Neither trophic modes of plankton nor its vertical evolutionary history could completely explain the functional repertoire convergence of major eukaryotic lineages that coexisted within oceanic currents for millions of years.
Published: 2022

15. Functional repertoire convergence of distantly related eukaryotic plankton lineages abundant in the sunlit ocean

Author: Delmont, Tom O., Gaia, Morgan, Hinsinger, Damien D., Frémont, Paul, Vanni, Chiara, Fernandez-Guerra, Antonio, Eren, A. Murat, Kourlaiev, Artem, d'Agata, Leo, Clayssen, Quentin, Villar, Emilie, Labadie, Karine, Cruaud, Corinne, Poulain, Julie, Da Silva, Corinne, Wessner, Marc, Noel, Benjamin, Aury, Jean-Marc, Sunagawa, Shinichi, Acinas, Silvia G., Bork, Peer, Karsenti, Eric, Bowler, Chris, Sardet, Christian, Stemmann, Lars, de Vargas, Colomban, Wincker, Patrick, Lescot, Magali, Babin, Marcel, Gorsky, Gabriel, Grimsley, Nigel, Guidi, Lionel, Hingamp, Pascal, Jaillon, Olivier, Kandels, Stefanie, Iudicone, Daniele, Ogata, Hiroyuki, Pesant, Stéphane, Sullivan, Matthew B., Not, Fabrice, Lee, Karp Boss, Boss, Emmanuel, Cochrane, Guy, Follows, Michael, Poulton, Nicole, Raes, Jeroen, Sieracki, Mike, Speich, Sabrina, Pelletier, Eric, Delmont, Tom O., Gaia, Morgan, Hinsinger, Damien D., Frémont, Paul, Vanni, Chiara, Fernandez-Guerra, Antonio, Eren, A. Murat, Kourlaiev, Artem, d'Agata, Leo, Clayssen, Quentin, Villar, Emilie, Labadie, Karine, Cruaud, Corinne, Poulain, Julie, Da Silva, Corinne, Wessner, Marc, Noel, Benjamin, Aury, Jean-Marc, Sunagawa, Shinichi, Acinas, Silvia G., Bork, Peer, Karsenti, Eric, Bowler, Chris, Sardet, Christian, Stemmann, Lars, de Vargas, Colomban, Wincker, Patrick, Lescot, Magali, Babin, Marcel, Gorsky, Gabriel, Grimsley, Nigel, Guidi, Lionel, Hingamp, Pascal, Jaillon, Olivier, Kandels, Stefanie, Iudicone, Daniele, Ogata, Hiroyuki, Pesant, Stéphane, Sullivan, Matthew B., Not, Fabrice, Lee, Karp Boss, Boss, Emmanuel, Cochrane, Guy, Follows, Michael, Poulton, Nicole, Raes, Jeroen, Sieracki, Mike, Speich, Sabrina, and Pelletier, Eric
Abstract: Marine planktonic eukaryotes play critical roles in global biogeochemical cycles and climate. However, their poor representation in culture collections limits our understanding of the evolutionary history and genomic underpinnings of planktonic ecosystems. Here, we used 280 billion Tara Oceans metagenomic reads from polar, temperate, and tropical sunlit oceans to reconstruct and manually curate more than 700 abundant and widespread eukaryotic environmental genomes ranging from 10 Mbp to 1.3 Gbp. This genomic resource covers a wide range of poorly characterized eukaryotic lineages that complement long-standing contributions from culture collections while better representing plankton in the upper layer of the oceans. We performed the first, to our knowledge, comprehensive genome-wide functional classification of abundant unicellular eukaryotic plankton, revealing four major groups connecting distantly related lineages. Neither trophic modes of plankton nor its vertical evolutionary history could completely explain the functional repertoire convergence of major eukaryotic lineages that coexisted within oceanic currents for millions of years.
Published: 2022

16. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity:effect of biotin and prebiotic supplementation on improved metabolism

Author: Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, Clement, Karine, Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifiti, Edi, Aron-Wisnewsky, Judith, Debedat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloe, Andre, Sebastien, Andreelli, Fabrizio, Blueher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue H., Holmes, Bridget, Ji, Boyang, Pedersen, Helle Krogh, Phuong Le, Le Chatelier, Emmanuelle, Lewinter, Christian, Manneras-Holm, Louise, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B., Touch, Sothea, Vieira-Silva, Sara, Galan, Pilar, Holst, Jens, Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Hercberg, Serge, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Ehrlich, Stanislav Dusko, Zucker, Jean-Daniel, Baeckhed, Fredrik, Raes, Jeroen, and Clement, Karine
Published: 2022

17. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author: Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe Elie, Schmidt, Thomas S.B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc Emmanuel, Ehrlich, S. Dusko, Pedersen, Oluf, Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe Elie, Schmidt, Thomas S.B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc Emmanuel, Ehrlich, S. Dusko, and Pedersen, Oluf
Abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
Published: 2022

18. The Incidence and Characteristics of Venous Thromboembolisms in Paediatric-Onset Inflammatory Bowel Disease:A Prospective International Cohort Study Based on the PIBD-SETQuality Safety Registry

Author: Aardoom, Martine A., Klomberg, Renz C.W., Kemos, Polychronis, Ruemmele, Frank M., Fagbemi, Andrew, Kiparissi, Fevronia, Schweizer, Joachim J., Sebastian, Shaji, Russell, Richard, Torrente, Franco, Van Mill, Marije, De Ridder, Lissy, Croft, Nicholas, Tempia-Caliera, Michela, Lee, Way Seah, Pigott, Anna J., Classen, Martin, Morris, Mary Anne, Muhammed, Rafeeq, Hussey, Seamus, Cananzi, Mara, Menz, Timothy J., Wahbeh, Ghassan T., Van Ommen, C. H.Heleen, Turner, Dan, Focht, Gili, Samsom, Janneke, Veereman, Gigi, Neyt, Mattias, Koletzko, Sibylle, Brückner, Annecarin, Levine, Arie, Weiner, Dror, Griffiths, Anne, Aloi, Marina, Raes, Jeroen, Christiaens, Annick, Walters, Thomas, Walker, Michael, Ruemelle, Frank, Demange, Christine Nguyen, Bigot, Laetitia, Aardoom, Martine A., Klomberg, Renz C.W., Kemos, Polychronis, Ruemmele, Frank M., Fagbemi, Andrew, Kiparissi, Fevronia, Schweizer, Joachim J., Sebastian, Shaji, Russell, Richard, Torrente, Franco, Van Mill, Marije, De Ridder, Lissy, Croft, Nicholas, Tempia-Caliera, Michela, Lee, Way Seah, Pigott, Anna J., Classen, Martin, Morris, Mary Anne, Muhammed, Rafeeq, Hussey, Seamus, Cananzi, Mara, Menz, Timothy J., Wahbeh, Ghassan T., Van Ommen, C. H.Heleen, Turner, Dan, Focht, Gili, Samsom, Janneke, Veereman, Gigi, Neyt, Mattias, Koletzko, Sibylle, Brückner, Annecarin, Levine, Arie, Weiner, Dror, Griffiths, Anne, Aloi, Marina, Raes, Jeroen, Christiaens, Annick, Walters, Thomas, Walker, Michael, Ruemelle, Frank, Demange, Christine Nguyen, and Bigot, Laetitia
Abstract: Background and Aims: Guidelines regarding thromboprophylaxis for venous thromboembolisms [VTEs] in children with inflammatory bowel disease [IBD] are based on limited paediatric evidence. We aimed to prospectively assess the incidence of VTEs in paediatric-onset IBD [PIBD], characterize PIBD patients with a VTE and identify potential IBD-related risk factors. Methods: From October 2016 to September 2020, paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. IBD details [type, Paris classification, clinical and biochemical disease activity, treatment] and VTE details [type, location, treatment, outcome] were collected. To estimate VTE incidence, participants annually reported the number of PIBD patients, data source and catchment area of their centre. A systematic literature review and meta-analysis was performed to calculate the VTE incidence in the general paediatric population. Results: Participation of 129 PIBD centres resulted in coverage of 24 802 PIBD patients. Twenty cases of VTE were identified [30% Crohn's disease]. The incidence of VTEs was 3.72 (95% confidence interval [CI] 2.27-5.74) per 10 000 person-years, 14-fold higher than in the general paediatric population (0.27 [95% CI 0.18-0.38], p < 0.001). Cerebral sinus venous thrombosis was most frequently reported [50%]. All but one patient had active IBD, 45% were using steroids and 45% were hospitalized. No patient received thromboprophylaxis, whereas according to current PIBD guidelines, this was recommended in 4/20 patients. Conclusion: There is an increased risk of VTEs in the PIBD population compared to the general paediatric population. Awareness of VTE occurrence and prevention should be extended to all PIBD patients with active disease, especially those hospitalized.
Published: 2022

19. Microbiome and metabolome features of the cardiometabolic disease spectrum

Author: Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe Elie, Schmidt, Thomas S.B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc Emmanuel, Ehrlich, S. Dusko, Pedersen, Oluf, Fromentin, Sebastien, Forslund, Sofia K., Chechi, Kanta, Aron-Wisnewsky, Judith, Chakaroun, Rima, Nielsen, Trine, Tremaroli, Valentina, Ji, Boyang, Prifti, Edi, Myridakis, Antonis, Chilloux, Julien, Andrikopoulos, Petros, Fan, Yong, Olanipekun, Michael T., Alves, Renato, Adiouch, Solia, Bar, Noam, Talmor-Barkan, Yeela, Belda, Eugeni, Caesar, Robert, Coelho, Luis Pedro, Falony, Gwen, Fellahi, Soraya, Galan, Pilar, Galleron, Nathalie, Helft, Gerard, Hoyles, Lesley, Isnard, Richard, Le Chatelier, Emmanuelle, Julienne, Hanna, Olsson, Lisa, Pedersen, Helle Krogh, Pons, Nicolas, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe Elie, Schmidt, Thomas S.B., Vieira-Silva, Sara, Li, Peishun, Zimmermann-Kogadeeva, Maria, Lewinter, Christian, Søndertoft, Nadja B., Hansen, Tue H., Gauguier, Dominique, Gøtze, Jens Peter, Køber, Lars, Kornowski, Ran, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean Daniel, Hercberg, Serge, Letunic, Ivica, Bäckhed, Fredrik, Oppert, Jean Michel, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Stumvoll, Michael, Segal, Eran, Clément, Karine, Dumas, Marc Emmanuel, Ehrlich, S. Dusko, and Pedersen, Oluf
Abstract: Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
Published: 2022

20. Macroscale patterns of oceanic zooplankton composition and size structure

Author: Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, Winckler, Patrick, Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, and Winckler, Patrick
Abstract: Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
Published: 2021
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21. Macroscale patterns of oceanic zooplankton composition and size structure

Author: Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, Winckler, Patrick, Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, and Winckler, Patrick
Abstract: Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
Published: 2021
Full Text: View/download PDF

22. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities

Author: Ministerio de Economía y Competitividad (España), Department of Energy (US), Ministerio de Ciencia, Innovación y Universidades (España), Generalitat de Catalunya, Agencia Estatal de Investigación (España), King Abdullah University of Science and Technology, European Commission, Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M., Arrieta López de Uralde, Jesús M., Alam, Intikhab, Kamau, Allan A., Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., Gasol, Josep M., Ministerio de Economía y Competitividad (España), Department of Energy (US), Ministerio de Ciencia, Innovación y Universidades (España), Generalitat de Catalunya, Agencia Estatal de Investigación (España), King Abdullah University of Science and Technology, European Commission, Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M., Arrieta López de Uralde, Jesús M., Alam, Intikhab, Kamau, Allan A., Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., and Gasol, Josep M.
Abstract: The deep sea, the largest ocean’s compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem
Published: 2021

23. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities.

Author: Acinas, Silvia G, Acinas, Silvia G, Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M, Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M, Arrieta, Jesús M, Alam, Intikhab S, Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B, Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M, Gasol, Josep M, Acinas, Silvia G, Acinas, Silvia G, Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M, Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M, Arrieta, Jesús M, Alam, Intikhab S, Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B, Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M, and Gasol, Josep M
Abstract: The deep sea, the largest ocean's compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
Published: 2021

24. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities

Author: Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M., Arrieta, Jesús M., Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., Gasol, Josep M., Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M., Arrieta, Jesús M., Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., and Gasol, Josep M.
Abstract: The deep sea, the largest ocean’s compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
Published: 2021

25. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author: Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, MiBioGen Consortium Initiative, Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, and MiBioGen Consortium Initiative
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Published: 2021
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26. Reporting guidelines for human microbiome research: the STORMS checklist

Author: Mirzayi, Chloe, Renson, Audrey, Zohra, Fatima, Elsafoury, Shaimaa, Geistlinger, Ludwig, Kasselman, Lora J., Eckenrode, Kelly, van de Wijgert, Janneke, Loughman, Amy, Marques, Francine Z., MacIntyre, David A., Arumugam, Manimozhiyan, Azhar, Rimsha, Beghini, Francesco, Bergstrom, Kirk, Bhatt, Ami, Bisanz, Jordan E., Braun, Jonathan, Bravo, Hector Corrada, Buck, Gregory A., Bushman, Frederic, Casero, David, Clarke, Gerard, Carmen Collado, Maria, Cotter, Paul D., Cryan, John F., Demmer, Ryan T., Devkota, Suzanne, Elinav, Eran, Escobar, Juan S., Fettweis, Jennifer, Finn, Robert D., Fodor, Anthony A., Forslund, Sofia, Franke, Andre, Furlanello, Cesare, Gilbert, Jack, Grice, Elizabeth, Haibe-Kains, Benjamin, Handley, Scott, Herd, Pamela, Holmes, Susan, Jacobs, Jonathan P., Karstens, Lisa, Knight, Rob, Knights, Dan, Koren, Omry, Kwon, Douglas S., Langille, Morgan, Lindsay, Brianna, McGovern, Dermot, McHardy, Alice C., McWeeney, Shannon, Mueller, Noel T., Nezi, Luigi, Olm, Matthew, Palm, Noah, Pasolli, Edoardo, Raes, Jeroen, Redinbo, Matthew R., Ruhlemann, Malte, Sartor, R. Balfour, Schloss, Patrick D., Schriml, Lynn, Segal, Eran, Shardell, Michelle, Sharpton, Thomas, Smirnova, Ekaterina, Sokol, Harry, Sonnenburg, Justin L., Srinivasan, Sujatha, Thingholm, Louise B., Turnbaugh, Peter J., Upadhyay, Vaibhav, Walls, Ramona L., Wilmes, Paul, Yamada, Takuji, Zeller, Georg, Zhang, Mingyu, Zhao, Ni, Zhao, Liping, Bao, Wenjun, Culhane, Aedin, Devanarayan, Viswanath, Dopazo, Joaquin, Fan, Xiaohui, Fischer, Matthias, Jones, Wendell, Kusko, Rebecca, Mason, Christopher E., Mercer, Tim R., Sansone, Susanna-Assunta, Scherer, Andreas, Shi, Leming, Thakkar, Shraddha, Tong, Weida, Wolfinger, Russ, Hunter, Christopher, Segata, Nicola, Huttenhower, Curtis, Dowd, Jennifer B., Jones, Heidi E., Waldron, Levi, Mirzayi, Chloe, Renson, Audrey, Zohra, Fatima, Elsafoury, Shaimaa, Geistlinger, Ludwig, Kasselman, Lora J., Eckenrode, Kelly, van de Wijgert, Janneke, Loughman, Amy, Marques, Francine Z., MacIntyre, David A., Arumugam, Manimozhiyan, Azhar, Rimsha, Beghini, Francesco, Bergstrom, Kirk, Bhatt, Ami, Bisanz, Jordan E., Braun, Jonathan, Bravo, Hector Corrada, Buck, Gregory A., Bushman, Frederic, Casero, David, Clarke, Gerard, Carmen Collado, Maria, Cotter, Paul D., Cryan, John F., Demmer, Ryan T., Devkota, Suzanne, Elinav, Eran, Escobar, Juan S., Fettweis, Jennifer, Finn, Robert D., Fodor, Anthony A., Forslund, Sofia, Franke, Andre, Furlanello, Cesare, Gilbert, Jack, Grice, Elizabeth, Haibe-Kains, Benjamin, Handley, Scott, Herd, Pamela, Holmes, Susan, Jacobs, Jonathan P., Karstens, Lisa, Knight, Rob, Knights, Dan, Koren, Omry, Kwon, Douglas S., Langille, Morgan, Lindsay, Brianna, McGovern, Dermot, McHardy, Alice C., McWeeney, Shannon, Mueller, Noel T., Nezi, Luigi, Olm, Matthew, Palm, Noah, Pasolli, Edoardo, Raes, Jeroen, Redinbo, Matthew R., Ruhlemann, Malte, Sartor, R. Balfour, Schloss, Patrick D., Schriml, Lynn, Segal, Eran, Shardell, Michelle, Sharpton, Thomas, Smirnova, Ekaterina, Sokol, Harry, Sonnenburg, Justin L., Srinivasan, Sujatha, Thingholm, Louise B., Turnbaugh, Peter J., Upadhyay, Vaibhav, Walls, Ramona L., Wilmes, Paul, Yamada, Takuji, Zeller, Georg, Zhang, Mingyu, Zhao, Ni, Zhao, Liping, Bao, Wenjun, Culhane, Aedin, Devanarayan, Viswanath, Dopazo, Joaquin, Fan, Xiaohui, Fischer, Matthias, Jones, Wendell, Kusko, Rebecca, Mason, Christopher E., Mercer, Tim R., Sansone, Susanna-Assunta, Scherer, Andreas, Shi, Leming, Thakkar, Shraddha, Tong, Weida, Wolfinger, Russ, Hunter, Christopher, Segata, Nicola, Huttenhower, Curtis, Dowd, Jennifer B., Jones, Heidi E., and Waldron, Levi
Abstract: The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results. The STORMS tool provides guidance for concise and complete reporting of microbiome studies to facilitate manuscript preparation, peer review, reader comprehension of publications, and comparative analysis of published results.
Published: 2021

27. Local immune response to food antigens drives meal-induced abdominal pain

Author: Afd Pharmacology, Pharmacology, Aguilera-Lizarraga, Javier, Florens, Morgane V, Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U, Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A, Feyerabend, Thorsten B, Rodewald, Hans-Reimer, Farre, Ricard, Redegeld, Frank A, Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N, Boyd, Scott D, Hoh, Ramona A, Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E, Vanner, Stephen J, Denadai-Souza, Alexandre, Wouters, Mira M, Boeckxstaens, Guy E, Afd Pharmacology, Pharmacology, Aguilera-Lizarraga, Javier, Florens, Morgane V, Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U, Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A, Feyerabend, Thorsten B, Rodewald, Hans-Reimer, Farre, Ricard, Redegeld, Frank A, Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N, Boyd, Scott D, Hoh, Ramona A, Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E, Vanner, Stephen J, Denadai-Souza, Alexandre, Wouters, Mira M, and Boeckxstaens, Guy E
Published: 2021

28. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author: Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A., Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A., Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, D’Amato, Mauro, Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A., Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A., Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and D’Amato, Mauro
Abstract: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
Published: 2021
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29. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author: Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, DAmato, Mauro, Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and DAmato, Mauro
Abstract: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes., Funding agencies: he Swedish Research Council (VR 2017-02403), the Health Department of the Basque Government (2015111133), and the Spanish Ministry of Economy and Competitiveness (FIS PI17/00308) to M.D.; the research leading to these results has received funding from the EU FP7 under grant nr. 313010 (BBMRI-LPC); the FGFP project received support from the Flemish government (IWT130359), the Research Fund–Flanders (FWO) Odysseus program (G.0924.09), the King Baudouin Foundation (2012-J80000-004), FP7 METACARDIS HEALTH-F4-2012-305312, VIB, the Rega Institute for Medical Research, and KU Leuven. R.B. is funded by the Research Fund–Flanders (FWO) through a postdoctoral fellowship (1221620N). A.Z. is supported by the ERC Starting Grant 715772, Netherlands Organization for Scientific Research NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and the NWO Gravitation grant ExposomeNL 024.004.017.
Published: 2021
Full Text: View/download PDF

30. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author: Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, DAmato, Mauro, Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and DAmato, Mauro
Abstract: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes., Funding agencies: he Swedish Research Council (VR 2017-02403), the Health Department of the Basque Government (2015111133), and the Spanish Ministry of Economy and Competitiveness (FIS PI17/00308) to M.D.; the research leading to these results has received funding from the EU FP7 under grant nr. 313010 (BBMRI-LPC); the FGFP project received support from the Flemish government (IWT130359), the Research Fund–Flanders (FWO) Odysseus program (G.0924.09), the King Baudouin Foundation (2012-J80000-004), FP7 METACARDIS HEALTH-F4-2012-305312, VIB, the Rega Institute for Medical Research, and KU Leuven. R.B. is funded by the Research Fund–Flanders (FWO) through a postdoctoral fellowship (1221620N). A.Z. is supported by the ERC Starting Grant 715772, Netherlands Organization for Scientific Research NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and the NWO Gravitation grant ExposomeNL 024.004.017.
Published: 2021
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31. Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin

Author: UCL - SSS/LDRI - Louvain Drug Research Institute, Suriano, Francesco, Vieira-Silva, Sara, Falony, Gwen, Roumain, Martin, Paquot, Adrien, Pelicaen, Rudy, Régnier, Marion, Delzenne, Nathalie M., Raes, Jeroen, Muccioli, Giulio, Van Hul, Matthias, Cani, Patrice D., UCL - SSS/LDRI - Louvain Drug Research Institute, Suriano, Francesco, Vieira-Silva, Sara, Falony, Gwen, Roumain, Martin, Paquot, Adrien, Pelicaen, Rudy, Régnier, Marion, Delzenne, Nathalie M., Raes, Jeroen, Muccioli, Giulio, Van Hul, Matthias, and Cani, Patrice D.
Abstract: Background: Leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice are commonly used mice models mimicking the conditions of obesity and type 2 diabetes development. However, although ob/ob and db/db mice are similarly gaining weight and developing massive obesity, db/db mice are more diabetic than ob/ob mice. It remains still unclear why targeting the same pathway-leptin signaling-leads to the development of two different phenotypes. Given that gut microbes dialogue with the host via different metabolites (e.g., short-chain fatty acids) but also contribute to the regulation of bile acids metabolism, we investigated whether inflammatory markers, bacterial components, bile acids, short-chain fatty acids, and gut microbes could contribute to explain the specific phenotype discriminating the onset of an obese and/or a diabetic state in ob/ob and db/db mice. Results: Six-week-old ob/ob and db/db mice were followed for 7 weeks; they had comparable body weight, fat mass, and lean mass gain, confirming their severely obese status. However, as expected, the glucose metabolism and the glucose-induced insulin secretion were significantly different between ob/ob and db/db mice. Strikingly, the fat distribution was different, with db/db mice having more subcutaneous and ob/ob mice having more epididymal fat. In addition, liver steatosis was more pronounced in the ob/ob mice than in db/db mice. We also found very distinct inflammatory profiles between ob/ob and db/db mice, with a more pronounced inflammatory tone in the liver for ob/ob mice as compared to a higher inflammatory tone in the (subcutaneous) adipose tissue for db/db mice. When analyzing the gut microbiota composition, we found that the quantity of 19 microbial taxa was in some way affected by the genotype. Furthermore, we also show that serum LPS concentration, hepatic bile acid content, and cecal short-chain fatty acid profiles were differently affected by the two genotypes. Conclusion: Taken together
Published: 2021

32. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities

Author: UCL - SST/LIBST - Louvain Institute of Biomolecular Science and Technology, Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima Mendez, Gipsi, Roux, Simon, González, José M., Arrieta, Jesús M., Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., Gasol, Josep M., UCL - SST/LIBST - Louvain Institute of Biomolecular Science and Technology, Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima Mendez, Gipsi, Roux, Simon, González, José M., Arrieta, Jesús M., Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., and Gasol, Josep M.
Abstract: The deep sea, the largest ocean’s compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
Published: 2021

33. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities.

Author: Acinas, Silvia G, Acinas, Silvia G, Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M, Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M, Arrieta, Jesús M, Alam, Intikhab S, Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B, Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M, Gasol, Josep M, Acinas, Silvia G, Acinas, Silvia G, Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M, Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M, Arrieta, Jesús M, Alam, Intikhab S, Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B, Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M, and Gasol, Josep M
Abstract: The deep sea, the largest ocean's compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
Published: 2021

34. Local immune response to food antigens drives meal-induced abdominal pain

Author: Afd Pharmacology, Pharmacology, Aguilera-Lizarraga, Javier, Florens, Morgane V, Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U, Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A, Feyerabend, Thorsten B, Rodewald, Hans-Reimer, Farre, Ricard, Redegeld, Frank A, Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N, Boyd, Scott D, Hoh, Ramona A, Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E, Vanner, Stephen J, Denadai-Souza, Alexandre, Wouters, Mira M, Boeckxstaens, Guy E, Afd Pharmacology, Pharmacology, Aguilera-Lizarraga, Javier, Florens, Morgane V, Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U, Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A, Feyerabend, Thorsten B, Rodewald, Hans-Reimer, Farre, Ricard, Redegeld, Frank A, Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N, Boyd, Scott D, Hoh, Ramona A, Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E, Vanner, Stephen J, Denadai-Souza, Alexandre, Wouters, Mira M, and Boeckxstaens, Guy E
Published: 2021

35. Macroscale patterns of oceanic zooplankton composition and size structure

Author: Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, Winckler, Patrick, Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, and Winckler, Patrick
Abstract: Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
Published: 2021
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36. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author: Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline, Garay, Juan Antonio Raygoza, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria, Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Ruhlemann, Malte C., Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lull, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret, Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W. V., Joossens, Marie, Jorgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A. M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sorensen, Soren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Volker, Uwe, Volzke, Henry, Vosa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M. A. E., Vasquez, Alejandro Arias, de Geus, Eco J. C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D'Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline, Garay, Juan Antonio Raygoza, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria, Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Ruhlemann, Malte C., Turpin, Williams, Moon, Jee-Young, Kim, Han-Na, Lull, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret, Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W. V., Joossens, Marie, Jorgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A. M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sorensen, Soren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Volker, Uwe, Volzke, Henry, Vosa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm-Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M. A. E., Vasquez, Alejandro Arias, de Geus, Eco J. C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung-Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D'Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, and Zhernakova, Alexandra
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Published: 2021
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37. Reporting guidelines for human microbiome research: the STORMS checklist.

Author: Mirzayi, Chloe, Mirzayi, Chloe, Renson, Audrey, Genomic Standards Consortium, Massive Analysis and Quality Control Society, Zohra, Fatima, Elsafoury, Shaimaa, Geistlinger, Ludwig, Kasselman, Lora J, Eckenrode, Kelly, van de Wijgert, Janneke, Loughman, Amy, Marques, Francine Z, MacIntyre, David A, Arumugam, Manimozhiyan, Azhar, Rimsha, Beghini, Francesco, Bergstrom, Kirk, Bhatt, Ami, Bisanz, Jordan E, Braun, Jonathan, Bravo, Hector Corrada, Buck, Gregory A, Bushman, Frederic, Casero, David, Clarke, Gerard, Collado, Maria Carmen, Cotter, Paul D, Cryan, John F, Demmer, Ryan T, Devkota, Suzanne, Elinav, Eran, Escobar, Juan S, Fettweis, Jennifer, Finn, Robert D, Fodor, Anthony A, Forslund, Sofia, Franke, Andre, Furlanello, Cesare, Gilbert, Jack, Grice, Elizabeth, Haibe-Kains, Benjamin, Handley, Scott, Herd, Pamela, Holmes, Susan, Jacobs, Jonathan P, Karstens, Lisa, Knight, Rob, Knights, Dan, Koren, Omry, Kwon, Douglas S, Langille, Morgan, Lindsay, Brianna, McGovern, Dermot, McHardy, Alice C, McWeeney, Shannon, Mueller, Noel T, Nezi, Luigi, Olm, Matthew, Palm, Noah, Pasolli, Edoardo, Raes, Jeroen, Redinbo, Matthew R, Rühlemann, Malte, Balfour Sartor, R, Schloss, Patrick D, Schriml, Lynn, Segal, Eran, Shardell, Michelle, Sharpton, Thomas, Smirnova, Ekaterina, Sokol, Harry, Sonnenburg, Justin L, Srinivasan, Sujatha, Thingholm, Louise B, Turnbaugh, Peter J, Upadhyay, Vaibhav, Walls, Ramona L, Wilmes, Paul, Yamada, Takuji, Zeller, Georg, Zhang, Mingyu, Zhao, Ni, Zhao, Liping, Bao, Wenjun, Culhane, Aedin, Devanarayan, Viswanath, Dopazo, Joaquin, Fan, Xiaohui, Fischer, Matthias, Jones, Wendell, Kusko, Rebecca, Mason, Christopher E, Mercer, Tim R, Sansone, Susanna-Assunta, Scherer, Andreas, Shi, Leming, Thakkar, Shraddha, Tong, Weida, Wolfinger, Russ, Hunter, Christopher, Mirzayi, Chloe, Mirzayi, Chloe, Renson, Audrey, Genomic Standards Consortium, Massive Analysis and Quality Control Society, Zohra, Fatima, Elsafoury, Shaimaa, Geistlinger, Ludwig, Kasselman, Lora J, Eckenrode, Kelly, van de Wijgert, Janneke, Loughman, Amy, Marques, Francine Z, MacIntyre, David A, Arumugam, Manimozhiyan, Azhar, Rimsha, Beghini, Francesco, Bergstrom, Kirk, Bhatt, Ami, Bisanz, Jordan E, Braun, Jonathan, Bravo, Hector Corrada, Buck, Gregory A, Bushman, Frederic, Casero, David, Clarke, Gerard, Collado, Maria Carmen, Cotter, Paul D, Cryan, John F, Demmer, Ryan T, Devkota, Suzanne, Elinav, Eran, Escobar, Juan S, Fettweis, Jennifer, Finn, Robert D, Fodor, Anthony A, Forslund, Sofia, Franke, Andre, Furlanello, Cesare, Gilbert, Jack, Grice, Elizabeth, Haibe-Kains, Benjamin, Handley, Scott, Herd, Pamela, Holmes, Susan, Jacobs, Jonathan P, Karstens, Lisa, Knight, Rob, Knights, Dan, Koren, Omry, Kwon, Douglas S, Langille, Morgan, Lindsay, Brianna, McGovern, Dermot, McHardy, Alice C, McWeeney, Shannon, Mueller, Noel T, Nezi, Luigi, Olm, Matthew, Palm, Noah, Pasolli, Edoardo, Raes, Jeroen, Redinbo, Matthew R, Rühlemann, Malte, Balfour Sartor, R, Schloss, Patrick D, Schriml, Lynn, Segal, Eran, Shardell, Michelle, Sharpton, Thomas, Smirnova, Ekaterina, Sokol, Harry, Sonnenburg, Justin L, Srinivasan, Sujatha, Thingholm, Louise B, Turnbaugh, Peter J, Upadhyay, Vaibhav, Walls, Ramona L, Wilmes, Paul, Yamada, Takuji, Zeller, Georg, Zhang, Mingyu, Zhao, Ni, Zhao, Liping, Bao, Wenjun, Culhane, Aedin, Devanarayan, Viswanath, Dopazo, Joaquin, Fan, Xiaohui, Fischer, Matthias, Jones, Wendell, Kusko, Rebecca, Mason, Christopher E, Mercer, Tim R, Sansone, Susanna-Assunta, Scherer, Andreas, Shi, Leming, Thakkar, Shraddha, Tong, Weida, Wolfinger, Russ, and Hunter, Christopher
Abstract: The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.
Published: 2021

38. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author: Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, DAmato, Mauro, Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and DAmato, Mauro
Abstract: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes., Funding agencies: he Swedish Research Council (VR 2017-02403), the Health Department of the Basque Government (2015111133), and the Spanish Ministry of Economy and Competitiveness (FIS PI17/00308) to M.D.; the research leading to these results has received funding from the EU FP7 under grant nr. 313010 (BBMRI-LPC); the FGFP project received support from the Flemish government (IWT130359), the Research Fund–Flanders (FWO) Odysseus program (G.0924.09), the King Baudouin Foundation (2012-J80000-004), FP7 METACARDIS HEALTH-F4-2012-305312, VIB, the Rega Institute for Medical Research, and KU Leuven. R.B. is funded by the Research Fund–Flanders (FWO) through a postdoctoral fellowship (1221620N). A.Z. is supported by the ERC Starting Grant 715772, Netherlands Organization for Scientific Research NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and the NWO Gravitation grant ExposomeNL 024.004.017.
Published: 2021
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39. Macroscale patterns of oceanic zooplankton composition and size structure

Author: Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, Winckler, Patrick, Costa Brandao, Manoela, Benedetti, Fabio, Martini, Séverine, Dodji Soviadan, Yawouvi, Irisson, Jean-olivier, Romagnan, Jean-baptiste, Elineau, Amanda, Desnos, Corinne, Jalabert, Laetitia, Freire, Andrea S, Picheral, Marc, Guidi, Lionel, Gorsky, Gabriel, Bowler, Chris, Karp-boss, Lee, Henry, Nicolas, De Vargas, Colomban, Sullivan, Matthew B, Tara Oceans Consortium Coordinators, Stemmann, Lars, Lombard, Fabien, Acinas, Silvia G, Babin, Marcel, Bork, Peer, Boss, Emmanuel, Cochrane, Guy, Grimsley, Nigel, Hingamp, Pascal, Ludicone, Daniele, Jaillon, Olivier, Kandels, Stefanie, Karsenti, Eric, Not, Fabrice, Ogata, Hiroyuki, Poultron, Nicole, Pesant, Stephane, Raes, Jeroen, Sardet, Christian, Speich, Sabrina, Sunagawa, Shinichi, and Winckler, Patrick
Abstract: Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
Published: 2021
Full Text: View/download PDF

40. Local immune response to food antigens drives meal-induced abdominal pain

Author: Afd Pharmacology, Pharmacology, Aguilera-Lizarraga, Javier, Florens, Morgane V, Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U, Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A, Feyerabend, Thorsten B, Rodewald, Hans-Reimer, Farre, Ricard, Redegeld, Frank A, Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N, Boyd, Scott D, Hoh, Ramona A, Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E, Vanner, Stephen J, Denadai-Souza, Alexandre, Wouters, Mira M, Boeckxstaens, Guy E, Afd Pharmacology, Pharmacology, Aguilera-Lizarraga, Javier, Florens, Morgane V, Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U, Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A, Feyerabend, Thorsten B, Rodewald, Hans-Reimer, Farre, Ricard, Redegeld, Frank A, Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N, Boyd, Scott D, Hoh, Ramona A, Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E, Vanner, Stephen J, Denadai-Souza, Alexandre, Wouters, Mira M, and Boeckxstaens, Guy E
Published: 2021

41. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities

Author: Acinas, Silvia, Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco, Logares, Ramiro, Royo-Lonch, Marta, Paoli, Lucas, Shinichi, Sunagawa, Hingamp, Pascal, Hiroyuki, Ogata, Lima-Mendez, Gipsi, Roux, Simón, González, José M., Arrieta, Jesús María, Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stèphane, Bork, Peer, Sebastián-Caumel, Marta, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramón, Duarte, Carlos Manuel, Gasol, Josep M, Acinas, Silvia, Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco, Logares, Ramiro, Royo-Lonch, Marta, Paoli, Lucas, Shinichi, Sunagawa, Hingamp, Pascal, Hiroyuki, Ogata, Lima-Mendez, Gipsi, Roux, Simón, González, José M., Arrieta, Jesús María, Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stèphane, Bork, Peer, Sebastián-Caumel, Marta, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramón, Duarte, Carlos Manuel, and Gasol, Josep M
Abstract: The deep sea, the largest ocean’s compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
Published: 2021

42. Deep ocean metagenomes provide insight into the metabolic architecture of bathypelagic microbial communities

Author: Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M., Arrieta, Jesús M., Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., Gasol, Josep M., Acinas, Silvia G., Sánchez, Pablo, Salazar, Guillem, Cornejo-Castillo, Francisco M., Sebastián, Marta, Logares, Ramiro, Royo-Llonch, Marta, Paoli, Lucas, Sunagawa, Shinichi, Hingamp, Pascal, Ogata, Hiroyuki, Lima-Mendez, Gipsi, Roux, Simon, González, José M., Arrieta, Jesús M., Alam, Intikhab S., Kamau, Allan, Bowler, Chris, Raes, Jeroen, Pesant, Stéphane, Bork, Peer, Agustí, Susana, Gojobori, Takashi, Vaqué, Dolors, Sullivan, Matthew B., Pedrós-Alió, Carlos, Massana, Ramon, Duarte, Carlos M., and Gasol, Josep M.
Abstract: The deep sea, the largest ocean’s compartment, drives planetary-scale biogeochemical cycling. Yet, the functional exploration of its microbial communities lags far behind other environments. Here we analyze 58 metagenomes from tropical and subtropical deep oceans to generate the Malaspina Gene Database. Free-living or particle-attached lifestyles drive functional differences in bathypelagic prokaryotic communities, regardless of their biogeography. Ammonia and CO oxidation pathways are enriched in the free-living microbial communities and dissimilatory nitrate reduction to ammonium and H2 oxidation pathways in the particle-attached, while the Calvin Benson-Bassham cycle is the most prevalent inorganic carbon fixation pathway in both size fractions. Reconstruction of the Malaspina Deep Metagenome-Assembled Genomes reveals unique non-cyanobacterial diazotrophic bacteria and chemolithoautotrophic prokaryotes. The widespread potential to grow both autotrophically and heterotrophically suggests that mixotrophy is an ecologically relevant trait in the deep ocean. These results expand our understanding of the functional microbial structure and metabolic capabilities of the largest Earth aquatic ecosystem.
Published: 2021

43. Reporting guidelines for human microbiome research: the STORMS checklist

Author: Mirzayi, Chloe, Renson, Audrey, Zohra, Fatima, Elsafoury, Shaimaa, Geistlinger, Ludwig, Kasselman, Lora J., Eckenrode, Kelly, van de Wijgert, Janneke, Loughman, Amy, Marques, Francine Z., MacIntyre, David A., Arumugam, Manimozhiyan, Azhar, Rimsha, Beghini, Francesco, Bergstrom, Kirk, Bhatt, Ami, Bisanz, Jordan E., Braun, Jonathan, Bravo, Hector Corrada, Buck, Gregory A., Bushman, Frederic, Casero, David, Clarke, Gerard, Carmen Collado, Maria, Cotter, Paul D., Cryan, John F., Demmer, Ryan T., Devkota, Suzanne, Elinav, Eran, Escobar, Juan S., Fettweis, Jennifer, Finn, Robert D., Fodor, Anthony A., Forslund, Sofia, Franke, Andre, Furlanello, Cesare, Gilbert, Jack, Grice, Elizabeth, Haibe-Kains, Benjamin, Handley, Scott, Herd, Pamela, Holmes, Susan, Jacobs, Jonathan P., Karstens, Lisa, Knight, Rob, Knights, Dan, Koren, Omry, Kwon, Douglas S., Langille, Morgan, Lindsay, Brianna, McGovern, Dermot, McHardy, Alice C., McWeeney, Shannon, Mueller, Noel T., Nezi, Luigi, Olm, Matthew, Palm, Noah, Pasolli, Edoardo, Raes, Jeroen, Redinbo, Matthew R., Ruhlemann, Malte, Sartor, R. Balfour, Schloss, Patrick D., Schriml, Lynn, Segal, Eran, Shardell, Michelle, Sharpton, Thomas, Smirnova, Ekaterina, Sokol, Harry, Sonnenburg, Justin L., Srinivasan, Sujatha, Thingholm, Louise B., Turnbaugh, Peter J., Upadhyay, Vaibhav, Walls, Ramona L., Wilmes, Paul, Yamada, Takuji, Zeller, Georg, Zhang, Mingyu, Zhao, Ni, Zhao, Liping, Bao, Wenjun, Culhane, Aedin, Devanarayan, Viswanath, Dopazo, Joaquin, Fan, Xiaohui, Fischer, Matthias, Jones, Wendell, Kusko, Rebecca, Mason, Christopher E., Mercer, Tim R., Sansone, Susanna-Assunta, Scherer, Andreas, Shi, Leming, Thakkar, Shraddha, Tong, Weida, Wolfinger, Russ, Hunter, Christopher, Segata, Nicola, Huttenhower, Curtis, Dowd, Jennifer B., Jones, Heidi E., Waldron, Levi, Mirzayi, Chloe, Renson, Audrey, Zohra, Fatima, Elsafoury, Shaimaa, Geistlinger, Ludwig, Kasselman, Lora J., Eckenrode, Kelly, van de Wijgert, Janneke, Loughman, Amy, Marques, Francine Z., MacIntyre, David A., Arumugam, Manimozhiyan, Azhar, Rimsha, Beghini, Francesco, Bergstrom, Kirk, Bhatt, Ami, Bisanz, Jordan E., Braun, Jonathan, Bravo, Hector Corrada, Buck, Gregory A., Bushman, Frederic, Casero, David, Clarke, Gerard, Carmen Collado, Maria, Cotter, Paul D., Cryan, John F., Demmer, Ryan T., Devkota, Suzanne, Elinav, Eran, Escobar, Juan S., Fettweis, Jennifer, Finn, Robert D., Fodor, Anthony A., Forslund, Sofia, Franke, Andre, Furlanello, Cesare, Gilbert, Jack, Grice, Elizabeth, Haibe-Kains, Benjamin, Handley, Scott, Herd, Pamela, Holmes, Susan, Jacobs, Jonathan P., Karstens, Lisa, Knight, Rob, Knights, Dan, Koren, Omry, Kwon, Douglas S., Langille, Morgan, Lindsay, Brianna, McGovern, Dermot, McHardy, Alice C., McWeeney, Shannon, Mueller, Noel T., Nezi, Luigi, Olm, Matthew, Palm, Noah, Pasolli, Edoardo, Raes, Jeroen, Redinbo, Matthew R., Ruhlemann, Malte, Sartor, R. Balfour, Schloss, Patrick D., Schriml, Lynn, Segal, Eran, Shardell, Michelle, Sharpton, Thomas, Smirnova, Ekaterina, Sokol, Harry, Sonnenburg, Justin L., Srinivasan, Sujatha, Thingholm, Louise B., Turnbaugh, Peter J., Upadhyay, Vaibhav, Walls, Ramona L., Wilmes, Paul, Yamada, Takuji, Zeller, Georg, Zhang, Mingyu, Zhao, Ni, Zhao, Liping, Bao, Wenjun, Culhane, Aedin, Devanarayan, Viswanath, Dopazo, Joaquin, Fan, Xiaohui, Fischer, Matthias, Jones, Wendell, Kusko, Rebecca, Mason, Christopher E., Mercer, Tim R., Sansone, Susanna-Assunta, Scherer, Andreas, Shi, Leming, Thakkar, Shraddha, Tong, Weida, Wolfinger, Russ, Hunter, Christopher, Segata, Nicola, Huttenhower, Curtis, Dowd, Jennifer B., Jones, Heidi E., and Waldron, Levi
Abstract: The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results. The STORMS tool provides guidance for concise and complete reporting of microbiome studies to facilitate manuscript preparation, peer review, reader comprehension of publications, and comparative analysis of published results.
Published: 2021

44. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author: Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, DAmato, Mauro, Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and DAmato, Mauro
Abstract: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes., Funding agencies: he Swedish Research Council (VR 2017-02403), the Health Department of the Basque Government (2015111133), and the Spanish Ministry of Economy and Competitiveness (FIS PI17/00308) to M.D.; the research leading to these results has received funding from the EU FP7 under grant nr. 313010 (BBMRI-LPC); the FGFP project received support from the Flemish government (IWT130359), the Research Fund–Flanders (FWO) Odysseus program (G.0924.09), the King Baudouin Foundation (2012-J80000-004), FP7 METACARDIS HEALTH-F4-2012-305312, VIB, the Rega Institute for Medical Research, and KU Leuven. R.B. is funded by the Research Fund–Flanders (FWO) through a postdoctoral fellowship (1221620N). A.Z. is supported by the ERC Starting Grant 715772, Netherlands Organization for Scientific Research NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and the NWO Gravitation grant ExposomeNL 024.004.017.
Published: 2021
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45. GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome

Author: Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, DAmato, Mauro, Bonfiglio, Ferdinando, Liu, Xingrong, Smillie, Christopher, Pandit, Anita, Kurilshikov, Alexander, Bacigalupe, Rodrigo, Zheng, Tenghao, Nim, Hieu, Garcia-Etxebarria, Koldo, Bujanda, Luis, Andreasson, Anna, Agreus, Lars, Walter, Susanna, Abecasis, Gonçalo, Eijsbouts, Chris, Jostins, Luke, Parkes, Miles, Hughes, David A, Timpson, Nicholas, Raes, Jeroen, Franke, Andre, Kennedy, Nicholas A, Regev, Aviv, Zhernakova, Alexandra, Simren, Magnus, Camilleri, Michael, and DAmato, Mauro
Abstract: Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes., Funding agencies: he Swedish Research Council (VR 2017-02403), the Health Department of the Basque Government (2015111133), and the Spanish Ministry of Economy and Competitiveness (FIS PI17/00308) to M.D.; the research leading to these results has received funding from the EU FP7 under grant nr. 313010 (BBMRI-LPC); the FGFP project received support from the Flemish government (IWT130359), the Research Fund–Flanders (FWO) Odysseus program (G.0924.09), the King Baudouin Foundation (2012-J80000-004), FP7 METACARDIS HEALTH-F4-2012-305312, VIB, the Rega Institute for Medical Research, and KU Leuven. R.B. is funded by the Research Fund–Flanders (FWO) through a postdoctoral fellowship (1221620N). A.Z. is supported by the ERC Starting Grant 715772, Netherlands Organization for Scientific Research NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and the NWO Gravitation grant ExposomeNL 024.004.017.
Published: 2021
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46. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author: Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, and Zhernakova, Alexandra
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Published: 2021

47. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author: Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, MiBioGen Consortium Initiative, Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, and MiBioGen Consortium Initiative
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Published: 2021
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48. Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health

Author: Brial, Francois, Chilloux, Julien, Nielsen, Trine, Vieira-Silva, Sara, Falony, Gwen, Andrikopoulos, Petros, Olanipekun, Michael, Hoyles, Lesley, Djouadi, Fatima, Neves, Ana L., Rodriguez-Martinez, Andrea, Mouawad, Ghiwa Ishac, Pons, Nicolas, Forslund, Sofia, Le-chatelier, Emmanuelle, Le Lay, Aurelie, Nicholson, Jeremy, Hansen, Torben, Hyotylainen, Tuulia, Clement, Karine, Oresic, Matej, Bork, Peer, Ehrlich, Stanislav Dusko, Raes, Jeroen, Pedersen, Oluf Borbye, Gauguier, Dominique, Dumas, Marc-Emmanuel, Brial, Francois, Chilloux, Julien, Nielsen, Trine, Vieira-Silva, Sara, Falony, Gwen, Andrikopoulos, Petros, Olanipekun, Michael, Hoyles, Lesley, Djouadi, Fatima, Neves, Ana L., Rodriguez-Martinez, Andrea, Mouawad, Ghiwa Ishac, Pons, Nicolas, Forslund, Sofia, Le-chatelier, Emmanuelle, Le Lay, Aurelie, Nicholson, Jeremy, Hansen, Torben, Hyotylainen, Tuulia, Clement, Karine, Oresic, Matej, Bork, Peer, Ehrlich, Stanislav Dusko, Raes, Jeroen, Pedersen, Oluf Borbye, Gauguier, Dominique, and Dumas, Marc-Emmanuel
Abstract: Objective Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. Design In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied H-1-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. Results In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. Conclusion Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
Published: 2021

49. Large-scale association analyses identify host factors influencing human gut microbiome composition

Author: Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, Zhernakova, Alexandra, Kurilshikov, Alexander, Medina-Gomez, Carolina, Bacigalupe, Rodrigo, Radjabzadeh, Djawad, Wang, Jun, Demirkan, Ayse, Le Roy, Caroline I., Raygoza Garay, Juan Antonio, Finnicum, Casey T., Liu, Xingrong, Zhernakova, Daria V., Bonder, Marc Jan, Hansen, Tue H., Frost, Fabian, Rühlemann, Malte C., Turpin, Williams, Moon, Jee Young, Kim, Han Na, Lüll, Kreete, Barkan, Elad, Shah, Shiraz A., Fornage, Myriam, Szopinska-Tokov, Joanna, Wallen, Zachary D., Borisevich, Dmitrii, Agreus, Lars, Andreasson, Anna, Bang, Corinna, Bedrani, Larbi, Bell, Jordana T., Bisgaard, Hans, Boehnke, Michael, Boomsma, Dorret I., Burk, Robert D., Claringbould, Annique, Croitoru, Kenneth, Davies, Gareth E., van Duijn, Cornelia M., Duijts, Liesbeth, Falony, Gwen, Fu, Jingyuan, van der Graaf, Adriaan, Hansen, Torben, Homuth, Georg, Hughes, David A., Ijzerman, Richard G., Jackson, Matthew A., Jaddoe, Vincent W.V., Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J., Lieb, Wolfgang, Lusis, Aldons J., Masclee, Ad A.M., Moll, Henriette A., Mujagic, Zlatan, Qibin, Qi, Rothschild, Daphna, Shin, Hocheol, Sørensen, Søren J., Steves, Claire J., Thorsen, Jonathan, Timpson, Nicholas J., Tito, Raul Y., Vieira-Silva, Sara, Völker, Uwe, Völzke, Henry, Võsa, Urmo, Wade, Kaitlin H., Walter, Susanna, Watanabe, Kyoko, Weiss, Stefan, Weiss, Frank U., Weissbrod, Omer, Westra, Harm Jan, Willemsen, Gonneke, Payami, Haydeh, Jonkers, Daisy M.A.E., Arias Vasquez, Alejandro, de Geus, Eco J.C., Meyer, Katie A., Stokholm, Jakob, Segal, Eran, Org, Elin, Wijmenga, Cisca, Kim, Hyung Lae, Kaplan, Robert C., Spector, Tim D., Uitterlinden, Andre G., Rivadeneira, Fernando, Franke, Andre, Lerch, Markus M., Franke, Lude, Sanna, Serena, D’Amato, Mauro, Pedersen, Oluf, Paterson, Andrew D., Kraaij, Robert, Raes, Jeroen, and Zhernakova, Alexandra
Abstract: To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10−10 < P < 5 × 10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
Published: 2021

50. Local immune response to food antigens drives meal-induced abdominal pain

Author: Aguilera-Lizarraga, Javier, Florens, Morgane V., Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U., Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A., Feyerabend, Thorsten B., Rodewald, Hans Reimer, Farre, Ricard, Redegeld, Frank A., Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N., Boyd, Scott D., Hoh, Ramona A., Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E., Vanner, Stephen J., Denadai-Souza, Alexandre, Wouters, Mira M., Boeckxstaens, Guy E., Aguilera-Lizarraga, Javier, Florens, Morgane V., Viola, Maria Francesca, Jain, Piyush, Decraecker, Lisse, Appeltans, Iris, Cuende-Estevez, Maria, Fabre, Naomi, Van Beek, Kim, Perna, Eluisa, Balemans, Dafne, Stakenborg, Nathalie, Theofanous, Stavroula, Bosmans, Goele, Mondelaers, Stéphanie U., Matteoli, Gianluca, Ibiza Martínez, Sales, Lopez-Lopez, Cintya, Jaramillo-Polanco, Josue, Talavera, Karel, Alpizar, Yeranddy A., Feyerabend, Thorsten B., Rodewald, Hans Reimer, Farre, Ricard, Redegeld, Frank A., Si, Jiyeon, Raes, Jeroen, Breynaert, Christine, Schrijvers, Rik, Bosteels, Cédric, Lambrecht, Bart N., Boyd, Scott D., Hoh, Ramona A., Cabooter, Deirdre, Nelis, Maxim, Augustijns, Patrick, Hendrix, Sven, Strid, Jessica, Bisschops, Raf, Reed, David E., Vanner, Stephen J., Denadai-Souza, Alexandre, Wouters, Mira M., and Boeckxstaens, Guy E.
Abstract: Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.
Published: 2021

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