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334 results on '"Falony, Gwen"'

2. 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, 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

Published
2023
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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, and Pedersen, Oluf

Published
2023
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5. Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility

Author

Caenepeel, Clara, Deleu, Sara, Vazquez Castellanos, Jorge Francisco, Arnauts, Kaline, Braekeleire, Sara, Machiels, Kathleen, Baert, Filip, Mana, Fazia, Pouillon, Lieven, Hindryckx, Pieter, Lobaton, Triana, Louis, Edouard, Franchimont, Denis, Verstockt, Bram, Ferrante, Marc, Sabino, João, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, and Vermeire, Séverine

Published
2024
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6. 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 WV, Joossens, Marie, Jørgensen, Torben, Keszthelyi, Daniel, Knight, Rob, Laakso, Markku, Laudes, Matthias, Launer, Lenore J, Lieb, Wolfgang, Lusis, Aldons J, Masclee, Ad AM, 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 MAE, Arias Vasquez, Alejandro, de Geus, Eco JC, 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, and Pedersen, Oluf

Subjects
Microbiology, Biological Sciences, Genetics, Human Genome, Biotechnology, Clinical Research, Digestive Diseases, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Adolescent, Adult, Bifidobacterium, Child, Child, Preschool, Cohort Studies, Female, Gastrointestinal Microbiome, Genetic Variation, Genome-Wide Association Study, Humans, Lactase, Linkage Disequilibrium, Male, Mendelian Randomization Analysis, Metabolism, Quantitative Trait Loci, RNA, Ribosomal, 16S, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
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

Published
2021

8. RIGOROUS DONOR SELECTION FOR FMT IN ACTIVE ULCERATIVE COLITIS: KEY LESSONS FROM A RANDOMIZED CONTROLLED TRIAL HALTED FOR FUTILITY

Author

Caenepeel, Clara, primary, Deleu, Sara, additional, Vazquez Castellanos, Jorge Francisco, additional, Arnauts, Kaline, additional, Braekeleire, Sara, additional, Machiels, Kathleen, additional, Baert, Filip, additional, Mana, Fazia, additional, Pouillon, Lieven, additional, Hindryckx, Pieter, additional, Lobaton, Triana, additional, Louis, Edouard, additional, Franchimont, Denis, additional, Verstockt, Bram, additional, Ferrante, Marc, additional, Sabino, João, additional, Vieira-Silva, Sara, additional, Falony, Gwen, additional, Raes, Jeroen, additional, and Vermeire, Séverine, additional

Published
2024
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10. 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, and Chilloux, Julien

Subjects
Microbiota (Symbiotic organisms) -- Physiological aspects, Pharmacology, Experimental, Metabolic diseases -- Drug therapy, Cardiovascular diseases -- Drug therapy, Dose-response relationship (Biochemistry) -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery.sup.1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease., Author(s): Sofia K. Forslund [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] [sup.6] , Rima Chakaroun [sup.7] , Maria Zimmermann-Kogadeeva [sup.1] , Lajos Markó [sup.2] [sup.4] [sup.5] , Judith Aron-Wisnewsky [sup.8] [sup.9] , [...]

Published
2021
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11. 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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17. 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, and Forslund, Sofia K.

Subjects
Microbiota (Symbiotic organisms) -- Control -- Causes of -- Analysis, Dysbiosis -- Drug therapy -- Distribution, Statins -- Dosage and administration, Overweight persons -- Diseases -- Analysis, Prevalence studies (Epidemiology) -- Analysis, Company distribution practices, Environmental issues, Science and technology, Zoology and wildlife conservation
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.sup.1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities.sup.1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease.sup.2. Reported changes in stool consistency.sup.3 and inflammation status.sup.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. A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs., Author(s): Sara Vieira-Silva [sup.1] [sup.2] , Gwen Falony [sup.1] [sup.2] , Eugeni Belda [sup.3] [sup.4] , Trine Nielsen [sup.5] , Judith Aron-Wisnewsky [sup.3] [sup.6] , Rima Chakaroun [sup.7] , Sofia [...]

Published
2020
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25. A Dual UHPLC-HRMS-Based Fecal Metabolomics and Lipidomics Analysis and Automated Data Processing Pipeline for Comprehensive Gut Phenotyping

Author

Vangeenderhuysen, Pablo, primary, Van Arnhem, Jasmien, additional, Pomian, Beata, additional, De Graeve, Marilyn, additional, De Commer, Lindsey, additional, Falony, Gwen, additional, Raes, Jeroen, additional, Zhernakova, Alexandra, additional, Fu, Jingyuan, additional, Hemeryck, Lieselot Y., additional, and Vanhaecke, Lynn, additional

Published
2023
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26. A Dual UHPLC-HRMS-Based Fecal Metabolomics and Lipidomics Analysis and Automated Data Processing Pipeline for Comprehen-sive Gut Phenotyping

Author

Vangeenderhuysen, Pablo, primary, Van Arnhem, Jasmien, additional, Pomian, Beata, additional, De Graeve, Marilyn, additional, De Commer, Lindsey, additional, Falony, Gwen, additional, Raes, Jeroen, additional, Zhernakova, Alexandra, additional, Fu, Jingyuan, additional, Hemeryck, Lieselot Y., additional, and Vanhaecke, Lynn, additional

Published
2023
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28. Population-level analysis of gut microbiome variation

Author

Falony, Gwen, Joossens, Marie, Vieira-Silva, Sara, Wang, Jun, Darzi, Youssef, Faust, Karoline, Kurilshikov, Alexander, Bonder, Marc Jan, Valles-Colomer, Mireia, Vandeputte, Doris, Tito, Raul Y., Chaffron, Samuel, Rymenans, Leen, Verspecht, Chloë, De Sutter, Lise, Lima-Mendez, Gipsi, D'hoe, Kevin, Jonckheere, Karl, Homola, Daniel, Garcia, Roberto, Tigchelaar, Ettje F., Eeckhaudt, Linda, Fu, Jingyuan, Henckaerts, Liesbet, Zhernakova, Alexandra, Wijmenga, Cisca, and Raes, Jeroen

Published
2016

29. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

Author

Zhernakova, Alexandra, Kurilshikov, Alexander, Bonder, Marc Jan, Tigchelaar, Ettje F., Schirmer, Melanie, Vatanen, Tommi, Mujagic, Zlatan, Vila, Arnau Vich, Falony, Gwen, Vieira-Silva, Sara, Wang, Jun, Imhann, Floris, Brandsma, Eelke, Jankipersadsing, Soesma A., Joossens, Marie, Cenit, Maria Carmen, Deelen, Patrick, Swertz, Morris A., study, LifeLines cohort, Weersma, Rinse K., Feskens, Edith J. M., Netea, Mihai G., Gevers, Dirk, Jonkers, Daisy, Franke, Lude, Aulchenko, Yurii S., Huttenhower, Curtis, Raes, Jeroen, Hofker, Marten H., Xavier, Ramnik J., Wijmenga, Cisca, and Fu, Jingyuan

Published
2016

30. Variation and transmission of the human gut microbiota across multiple familial generations

Author

Valles-Colomer, Mireia, Bacigalupe, Rodrigo, Vieira-Silva, Sara, Suzuki, Shinya, Darzi, Youssef, Tito, Raul Y., Yamada, Takuji, Segata, Nicola, Raes, Jeroen, and Falony, Gwen

Subjects
Adult, Microbiology (medical), 16S, Adolescent, Immunology, DIVERSITY, CHILDREN, Bacterial Physiological Phenomena, Applied Microbiology and Biotechnology, Microbiology, Article, Cohort Studies, LIKELIHOOD, Feces, Young Adult, RICHNESS, RNA, Ribosomal, 16S, REGRESSION, 80 and over, Genetics, Humans, Family, R PACKAGE, Preschool, Child, Aged, LEVEL ANALYSIS, Ribosomal, Aged, 80 and over, RISK, Science & Technology, Bacteria, Cell Biology, Child, Preschool, Female, Gastrointestinal Microbiome, Metagenomics, Middle Aged, Metagenome, CATALOG, BODY-MASS INDEX, RNA, Microbiome, Life Sciences & Biomedicine
Abstract

Although the composition and functional potential of the human gut microbiota evolve over the lifespan, kinship has been identified as a key covariate of microbial community diversification. However, to date, sharing of microbiota features within families has mostly been assessed between parents and their direct offspring. Here we investigate the potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (n = 102) spanning 3 to 5 generations over the same female bloodline. We observe microbiome community composition associated with kinship, with seven low abundant genera displaying familial distribution patterns. While kinship and current cohabitation emerge as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother–daughter pairs, decreasing with increasing daughter’s age and being higher among cohabiting pairs than those living apart. Although rare, we detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation., Quantitative metagenomic analyses of gut microbiomes reveals kinship, together with current cohabitation, as drivers of microbial community transmission and persistence between family members over three to five generations.

Published
2021

31. 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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35. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamineN-oxide with implications for heart and kidney disorders

Author

Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia, 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, Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Pedro Coelho, Luis, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Zucker, Jean-Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad, Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, Dumas, Marc-Emmanuel, Imperial College London, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universitätsklinikum Leipzig, European Molecular Biology Laboratory [Heidelberg] (EMBL), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Paris-Saclay Food and Bioproduct Engineering (SayFood), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Procédés biotechnologiques au service de l'environnement (UR PROSE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Charles Viollette (ICV) - ULR 7394 (ICV), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Institut Supérieur d'Agriculture-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaGenoPolis (MGP (US 1367)), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

ObjectivesThe host-microbiota co-metabolite trimethylamineN-oxide (TMAO) is linked to increased thrombotic and cardiovascular risks. Here we, sought to i) characterize which host variables contribute to fasting serum TMAO levels in real-life settings ii) identify potential actionable therapeutic means related to circulating TMAO.DesignWe applied “explainable” machine learning, univariate-, multivariate- and mediation analyses of fasting plasma TMAO concentration and a multitude of bioclinical phenotypes in 1,741 adult Europeans of the MetaCardis study. We expanded and validated our epidemiological findings in mechanistic studies in human renal fibroblasts and a murine model of kidney fibrosis following TMAO exposure.ResultsNext to age, kidney function was the primary variable predicting circulating TMAO in MetaCardis, with microbiota composition and diet playing minor, albeit significant roles. Mediation analysis revealed a causal relationship between TMAO and kidney function decline that strengthened at more severe stages of cardiometabolic disease. We corroborated our findings in preclinical models where TMAO exposure augmented conversion of human renal fibroblasts into myofibroblasts and increased kidney scarringin vivo. Mechanistically, TMAO aggravated kidney fibrosis due to ERK1/2 hyperactivation synergistically with TGF-β1 signaling. Consistent with our findings, patients receiving next-generation glucose-lowering drugs with reno-protective properties, had significantly lower circulating TMAO when compared to propensity-score matched control individuals.ConclusionAfter age, kidney function is the major determinant of fasting circulating TMAO in adults. Our findings of lower TMAO levels in individuals medicated with reno-protective anti-diabetic drugs suggests a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk that merits urgent investigation in human trials.Data availability statementRaw shotgun sequencing data that support the findings of this study have been deposited in the European Nucleotide Archive with accession codes PRJEB37249, PRJEB38742, PRJEB41311 and PRJEB46098. Serum NMR and urine NMR metabolome data have been uploaded to Metabolights with accession number MTBLS3429; serum GC-MS and isotopically quantified serum metabolites (UPLC–MS/MS) are available from MassIVE with accession numbers MSV000088042 and MSV000088043, respectively.

Published
2022

40. Human gut microbes impact host serum metabolome and insulin sensitivity

Author

Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Nielsen, Henrik Bjorn, Hyotylainen, Tuulia, Nielsen, Trine, Jensen, Benjamin A.H., Forslund, Kristoffer, Hildebrand, Falk, Prifti, Edi, Falony, Gwen, Le Chatelier, Emmanuelle, Levenez, Florence, Dore, Joel, Mattila, Ismo, Plichta, Damian R., Poho, Paivi, Hellgren, Lars I., Arumugam, Manimozhiyan, Sunagawa, Shinichi, Vieira-Silva, Sara, Jorgensen, Torben, Holm, Jacob Bak, Trost, Kajetan, Kristiansen, Karsten, Brix, Susanne, Raes, Jeroen, Wang, Jun, Hansen, Torben, Bork, Peer, Brunak, Soren, Oresic, Matej, Ehrlich, S. Dusko, and Pedersen, Oluf

Subjects
Insulin resistance -- Genetic aspects, Amino acids, Metabolic diseases, Cardiovascular diseases, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched- chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders., Insulin resistance (IR) and metabolic syndrome are risk factors for both type 2 diabetes and ischaemic cardiovascular diseases, pathologies that are in epidemic growth worldwide. Mounting evidence suggests a link [...]

Published
2016
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41. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

Author

Forslund, Kristoffer, Hildebrand, Falk, Nielsen, Trine, Falony, Gwen, Le Chatelier, Emmanuelle, Sunagawa, Shinichi, Prifti, Edi, Vieira-Silva, Sara, Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Arumugam, Manimozhiyan, Kristiansen, Karsten, Voigt, Anita Yvonne, Vestergaard, Henrik, Hercog, Rajna, Costea, Paul Igor, Kultima, Jens Roat, Li, Junhua, Jorgensen, Torben, Levenez, Florence, Dore, Joel, Nielsen, H. Bjorn, Brunak, Soren, Raes, Jeroen, Hansen, Torben, Wang, Jun, Ehrlich, S. Dusko, Bork, Peer, and Pedersen, Oluf

Subjects
Microbiota (Symbiotic organisms) -- Physiological aspects, Diabetes therapy -- Physiological aspects, Metformin -- Patient outcomes -- Physiological aspects, Type 2 diabetes -- Drug therapy -- Physiological aspects -- Patient outcomes, Environmental issues, Science and technology, Zoology and wildlife conservation, Drug therapy, Physiological aspects, Patient outcomes
Abstract

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported (1, 2). In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis (3, 4). Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa (3, 4). These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication., T2D is a disorder of elevated blood glucose levels (hyperglycaemia) primarily due to insulin resistance and inadequate insulin secretion, with rising global prevalence. Genetic and environmental risk factors are known, [...]

Published
2015

42. 440: STANDARDIZED FECAL MICROBIOTA TRANSPLANTATION THROUGH MICROBIOME-GUIDED DONOR SELECTION IN ACTIVE ULCERATIVE COLITIS PATIENTS: A RANDOMIZED, PLACEBO-CONTROLLED INTERVENTION STUDY

Author

Deleu, Sara, primary, Caenepeel, Clara, additional, Arnauts, Kaline, additional, Castellanos, Jorge Francisco Vazquez, additional, Braekeleire, Sara, additional, Machiels, Kathleen, additional, Baert, Filip J., additional, Mana, Fazia, additional, Pouillon, Lieven, additional, Hindryckx, Pieter, additional, Lobaton, Triana, additional, Louis, Edouard, additional, Franchimont, Denis, additional, Ferrante, Marc, additional, Sabino, João, additional, Vieira-Silva, Sara, additional, Falony, Gwen, additional, Raes, Jeroen, additional, and Vermeire, Severine, additional

Published
2022
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43. The virota and its transkingdom interactions in the healthy infant gut

Author

Beller, Leen, primary, Deboutte, Ward, additional, Vieira-Silva, Sara, additional, Falony, Gwen, additional, Tito, Raul Yhossef, additional, Rymenans, Leen, additional, Yinda, Claude Kwe, additional, Vanmechelen, Bert, additional, Van Espen, Lore, additional, Jansen, Daan, additional, Shi, Chenyan, additional, Zeller, Mark, additional, Maes, Piet, additional, Faust, Karoline, additional, Van Ranst, Marc, additional, Raes, Jeroen, additional, and Matthijnssens, Jelle, additional

Published
2022
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44. 731 FAECAL MICROBIOTA TRANSPLANTATION IN ACTIVE ULCERATIVE COLITIS: INSIGHTS FROM A RANDOMIZED CONTROLLED TRIAL HALTED FOR FUTILITY

Author

Deleu, Sara, Caenepeel, Clara, Castellanos, Jorge Francisco Vazquez, Arnauts, Kaline, Braekeleire, Sara, Machiels, Kathleen, Baert, Filip J., Franchimont, Denis, Louis, Edouard, Lobaton, Triana, Mana, Fazia, Pouillon, Lieven, Hindryckx, Pieter, Verstockt, Bram, Ferrante, Marc, Sabino, João, Vieira-Silva, Sara, Falony, Gwen, Raes, Jeroen, and Vermeire, Séverine

Published
2024
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45. Mo1911 MICROBIAL MARKERS IN GASTRIC CANCER: EXPLORING GASTRIC MICROBIOTA FOR PROGNOSTIC INSIGHTS AND EARLY DETECTION

Author

Miranda, Isabel, Vieira-Silva, Sara, Centelles-Lodeiro, Javier, Lopes, Catarina, Libânio, Diogo, Ferreira, António C., Silva, Cláudia, Falony, Gwen, Martins, Diana F., Barros, António d., Chaves, Jéssica, Ortigão, Raquel, De Sá, Inês Marques, Moreira, Adelino L., Pereira, Ana Carina, Dinis-Ribeiro, Mario J., and Pimentel-Nunes, Pedro

Published
2024
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46. Additional file 3 of Effect of cryopreservation medium conditions on growth and isolation of gut anaerobes from human faecal samples

Author

Biclot, Anaïs, Huys, Geert R. B., Bacigalupe, Rodrigo, D’hoe, Kevin, Vandeputte, Doris, Falony, Gwen, Tito, Raul Y., and Raes, Jeroen

Subjects
fluids and secretions, digestive, oral, and skin physiology
Abstract

Additional file 2: Figure S2: Spearman correlation heatmap of the faecal variables, no significance was observed.

Published
2022
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48. Additional file 11 of Effect of cryopreservation medium conditions on growth and isolation of gut anaerobes from human faecal samples

Author

Biclot, Anaïs, Huys, Geert R. B., Bacigalupe, Rodrigo, D’hoe, Kevin, Vandeputte, Doris, Falony, Gwen, Tito, Raul Y., and Raes, Jeroen

Abstract

Additional file 10: Supplementary Table S7: Summary of the number of isolates and the number of recovered sequences from 16S rDNA sequencing of the isolates per individual and preservation condition.

Published
2022
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50. 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, Commission of the European Communities, Medical Research Council (MRC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Inst Med, Dept Mol & Clin Med, Wallenberg Lab, University of Gothenburg (GU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (COMUE) (USPC), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bordeaux (UB), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Service de Diabétologie [CHU Pitié-Salpétrière], Laboratoire de chimie Macromoléculaire (CNRS UMR 5076), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Keck School of Medicine [Los Angeles], University of Southern California (USC), Nutrition et cerveau (U1213, U855), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Medicina Molecular, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK

Subjects
EXPRESSION, [SDV]Life Sciences [q-bio], Biotin, Endocrinology and Diabetes, Microbiology, DIET, Mice, Humans, Animals, Obesity, CHROMIUM PICOLINATE, Inflammation, Science & Technology, OVERWEIGHT, Gastroenterology & Hepatology, Gastroenterology, 1103 Clinical Sciences, Gastrointestinal Microbiome, Obesity, Morbid, MetaCardis Consortium, Mice, Inbred C57BL, nutrition, Prebiotics, Diabetes Mellitus, Type 2, Cardiovascular and Metabolic Diseases, micronutrients, Other Clinical Medicine, diabetes mellitus, Vitamin B Complex, 1114 Paediatrics and Reproductive Medicine, intestinal bacteria, HEALTH, Life Sciences & Biomedicine
Abstract

ObjectivesGut 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.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration numberNCT02059538.

Published
2022

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