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1. 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, and Pedersen, Oluf

Published
2022
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2. Combinatorial, additive and dose-dependent drug–microbiome associations

Author

Forslund, Sofia K., Chakaroun, Rima, Zimmermann-Kogadeeva, Maria, Markó, Lajos, Aron-Wisnewsky, Judith, Nielsen, Trine, Moitinho-Silva, Lucas, Schmidt, Thomas S. B., Falony, Gwen, Vieira-Silva, Sara, Adriouch, Solia, Alves, Renato J., Assmann, Karen, Bastard, Jean-Philippe, Birkner, Till, Caesar, Robert, Chilloux, Julien, Coelho, Luis Pedro, Fezeu, Leopold, Galleron, Nathalie, Helft, Gerard, Isnard, Richard, Ji, Boyang, Kuhn, Michael, Le Chatelier, Emmanuelle, Myridakis, Antonis, Olsson, Lisa, Pons, Nicolas, Prifti, Edi, Quinquis, Benoit, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Tremaroli, Valentina, Valles-Colomer, Mireia, Lewinter, Christian, Søndertoft, Nadja B., Pedersen, Helle Krogh, Hansen, Tue H., Gøtze, Jens Peter, Køber, Lars, Vestergaard, Henrik, Hansen, Torben, Zucker, Jean-Daniel, Hercberg, Serge, Oppert, Jean-Michel, Letunic, Ivica, Nielsen, Jens, Bäckhed, Fredrik, Ehrlich, S. Dusko, Dumas, Marc-Emmanuel, Raes, Jeroen, Pedersen, Oluf, Clément, Karine, Stumvoll, Michael, and Bork, Peer

Published
2021
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3. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults

Author

Hansen, Lea B. S., Roager, Henrik M., Søndertoft, Nadja B., Gøbel, Rikke J., Kristensen, Mette, Vallès-Colomer, Mireia, Vieira-Silva, Sara, Ibrügger, Sabine, Lind, Mads V., Mærkedahl, Rasmus B., Bahl, Martin I., Madsen, Mia L., Havelund, Jesper, Falony, Gwen, Tetens, Inge, Nielsen, Trine, Allin, Kristine H., Frandsen, Henrik L., Hartmann, Bolette, Holst, Jens Juul, Sparholt, Morten H., Holck, Jesper, Blennow, Andreas, Moll, Janne Marie, Meyer, Anne S., Hoppe, Camilla, Poulsen, Jørgen H., Carvalho, Vera, Sagnelli, Domenico, Dalgaard, Marlene D., Christensen, Anders F., Lydolph, Magnus Christian, Ross, Alastair B., Villas-Bôas, Silas, Brix, Susanne, Sicheritz-Pontén, Thomas, Buschard, Karsten, Linneberg, Allan, Rumessen, Jüri J., Ekstrøm, Claus T., Ritz, Christian, Kristiansen, Karsten, Nielsen, H. Bjørn, Vestergaard, Henrik, Færgeman, Nils J., Raes, Jeroen, Frøkiær, Hanne, Hansen, Torben, Lauritzen, Lotte, Gupta, Ramneek, Licht, Tine Rask, and Pedersen, Oluf

Published
2018
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4. 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., Prifti, Edi, Aron-Wisnewsky, Judith, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouya, Chloé, André, Sébastien, Andreelli,, Fabrizio, Blüher, Matthias Blüher, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue, Holmes, Bridget, Ji, Boyang, Krogh Pedersen, Helle, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Mannerås-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, Consortium, MetaCardis, 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, Stumvol, Michael, Pedersen, Oluf Borbye, Bork, Peer, Dusko Ehrlich, Stanislav, Zucker, Jens-Daniel, Bäckhed, Fredrik, Raes, Jeroen, Clément, Karine, Belda, Eugeni, Voland, Lise, Tremaroli, Valentina, Falony, Gwen, Adriouch, Solia, Assmann, Karen E., Prifti, Edi, Aron-Wisnewsky, Judith, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouya, Chloé, André, Sébastien, Andreelli,, Fabrizio, Blüher, Matthias Blüher, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Dao, Maria Carlota, Das, Promi, Fellahi, Soraya, Forslund, Sofia, Galleron, Nathalie, Hansen, Tue, Holmes, Bridget, Ji, Boyang, Krogh Pedersen, Helle, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Mannerås-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, Consortium, MetaCardis, 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, Stumvol, Michael, Pedersen, Oluf Borbye, Bork, Peer, Dusko Ehrlich, Stanislav, Zucker, Jens-Daniel, Bäckhed, Fredrik, Raes, Jeroen, and Clément, Karine

Abstract

Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.

Published
2022

5. 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

6. The intestinal microbiome is a co-determinant of the postprandial plasma glucose response

Author

Søndertoft, Nadja B., primary, Vogt, Josef K., additional, Arumugam, Manimozhiyan, additional, Kristensen, Mette, additional, Gøbel, Rikke J., additional, Fan, Yong, additional, Lyu, Liwei, additional, Bahl, Martin I., additional, Eriksen, Carsten, additional, Ängquist, Lars, additional, Frøkiær, Hanne, additional, Hansen, Tue H., additional, Brix, Susanne, additional, Nielsen, H. Bjørn, additional, Hansen, Torben, additional, Vestergaard, Henrik, additional, Gupta, Ramneek, additional, Licht, Tine R., additional, Lauritzen, Lotte, additional, and Pedersen, Oluf, additional

Published
2020
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7. The intestinal microbiome is a co-determinant of the postprandial plasma glucose response

Author

Søndertoft, Nadja B., Vogt, Josef K., Arumugam, Manimozhiyan, Kristensen, Mette, Gøbel, Rikke J., Fan, Yong, Lyu, Liwei, Bahl, Martin Iain, Eriksen, Carsten, Ängquist, Lars, Frøkiær, Hanne, Hansen, Tue H., Brix, Susanne, Nielsen, H. Bjørn, Hansen, Torben, Vestergaard, Henrik, Gupta, Ramneek, Licht, Tine Rask, Lauritzen, Lotte, Pedersen, Oluf, Søndertoft, Nadja B., Vogt, Josef K., Arumugam, Manimozhiyan, Kristensen, Mette, Gøbel, Rikke J., Fan, Yong, Lyu, Liwei, Bahl, Martin Iain, Eriksen, Carsten, Ängquist, Lars, Frøkiær, Hanne, Hansen, Tue H., Brix, Susanne, Nielsen, H. Bjørn, Hansen, Torben, Vestergaard, Henrik, Gupta, Ramneek, Licht, Tine Rask, Lauritzen, Lotte, and Pedersen, Oluf

Abstract

Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in

Published
2020

8. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

Author

Vieira-Silva, Sara, Falony, Gwen, Belda, Eugeni, Nielsen, Trine, Aron-Wisnewsky, Judith, Chakaroun, Rima, Forslund, Sofia K, Assmann, Karen, Valles-Colomer, Mireia, Nguyen, Thi Thuy Duyen, Proost, Sebastian, Prifti, Edi, Tremaroli, Valentina, Pons, Nicolas, Le Chatelier, Emmanuelle, Andreelli, Fabrizio, Bastard, Jean-Phillippe, Coelho, Luis Pedro, Galleron, Nathalie, Hansen, Tue H, Hulot, Jean-Sébastien, Lewinter, Christian, Pedersen, Helle K, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Søndertoft, Nadja B, Touch, Sothea, Dumas, Marc-Emmanuel, Ehrlich, Stanislav Dusko, Galan, Pilar, Gøtze, Jens P, Hansen, Torben, Holst, Jens J, Køber, Lars, Letunic, Ivica, Nielsen, Jens, Oppert, Jean-Michel, Stumvoll, Michael, Vestergaard, Henrik, Zucker, Jean-Daniel, Bork, Peer, Pedersen, Oluf, Bäckhed, Fredrik, Clément, Karine, Raes, Jeroen, Vieira-Silva, Sara, Falony, Gwen, Belda, Eugeni, Nielsen, Trine, Aron-Wisnewsky, Judith, Chakaroun, Rima, Forslund, Sofia K, Assmann, Karen, Valles-Colomer, Mireia, Nguyen, Thi Thuy Duyen, Proost, Sebastian, Prifti, Edi, Tremaroli, Valentina, Pons, Nicolas, Le Chatelier, Emmanuelle, Andreelli, Fabrizio, Bastard, Jean-Phillippe, Coelho, Luis Pedro, Galleron, Nathalie, Hansen, Tue H, Hulot, Jean-Sébastien, Lewinter, Christian, Pedersen, Helle K, Quinquis, Benoit, Rouault, Christine, Roume, Hugo, Salem, Joe-Elie, Søndertoft, Nadja B, Touch, Sothea, Dumas, Marc-Emmanuel, Ehrlich, Stanislav Dusko, Galan, Pilar, Gøtze, Jens P, Hansen, Torben, Holst, Jens J, Køber, Lars, Letunic, Ivica, Nielsen, Jens, Oppert, Jean-Michel, Stumvoll, Michael, Vestergaard, Henrik, Zucker, Jean-Daniel, Bork, Peer, Pedersen, Oluf, Bäckhed, Fredrik, Clément, Karine, and Raes, Jeroen

Abstract

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible

Published
2020

9. Integrative data analysis of genotype, microbiome and metabolomics for prediction of response to diet for improved metabolic health

Author

Nielsen, Rikke Linnemann, Helenius, Marianne, Muktupavela, Rasa, Jensen, Cecilia Bang, Hansen, Lea Benedicte Skov, Roager, Henrik Munch, Søndertoft, Nadja B., Vestergaard, Henrik, Hansen, Torben, Bahl, Martin Iain, Brix, Susanne, Kristiansen, Karsten, Licht, Tine Rask, Lauritzen, Lotte, Pedersen, Oluf, Gupta, Ramneek, Nielsen, Rikke Linnemann, Helenius, Marianne, Muktupavela, Rasa, Jensen, Cecilia Bang, Hansen, Lea Benedicte Skov, Roager, Henrik Munch, Søndertoft, Nadja B., Vestergaard, Henrik, Hansen, Torben, Bahl, Martin Iain, Brix, Susanne, Kristiansen, Karsten, Licht, Tine Rask, Lauritzen, Lotte, Pedersen, Oluf, and Gupta, Ramneek

Published
2018

11. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Author

Vieira-Silva S, Falony G, Belda E, Nielsen T, Aron-Wisnewsky J, Chakaroun R, Forslund SK, Assmann K, Valles-Colomer M, Nguyen TTD, Proost S, Prifti E, Tremaroli V, Pons N, Le Chatelier E, Andreelli F, Bastard JP, Coelho LP, Galleron N, Hansen TH, Hulot JS, Lewinter C, Pedersen HK, Quinquis B, Rouault C, Roume H, Salem JE, Søndertoft NB, Touch S, Dumas ME, Ehrlich SD, Galan P, Gøtze JP, Hansen T, Holst JJ, Køber L, Letunic I, Nielsen J, Oppert JM, Stumvoll M, Vestergaard H, Zucker JD, Bork P, Pedersen O, Bäckhed F, Clément K, and Raes J

Subjects
Bacteroides isolation & purification, Cohort Studies, Cross-Sectional Studies, Faecalibacterium isolation & purification, Feces microbiology, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Inflammatory Bowel Diseases microbiology, Male, Obesity microbiology, Prevalence, Dysbiosis epidemiology, Dysbiosis prevention & control, Gastrointestinal Microbiome drug effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Abstract

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans 1,2 . Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities 1,2 , and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease 2 . Reported changes in stool consistency 3 and inflammation status 4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

Published
2020
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