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

作者：Eugeni Belda, Lise Voland, Valentina Tremaroli, Gwen Falony, Solia Adriouch, Karen Elena Assmann, Edi Prifti, Judith Aron‐Wisnewsky, Jean Debédat, Tiphaine Le Roy, Trine Skov Nielsen, Chloé Amouyal, Sébastien André, Fabrizio Andreelli, Matthias Blüher, Rima Chakaroun, Julien Chilloux, Luis Pedro Coelho, Maria Carlota Dao, Promi Das, Soraya Fellahi, Sofia Kirke Forslund, Nathalie Galleron, Tue H. Hansen, Bridget Holmes, Boyang Ji, Helle Pedersen, Phuong Thi Le, Emmanuelle Le Chatelier, Christian Lewinter, Louise Mannerås-Holm, Florian Marquet, Antonis Myridakis, Véronique Pelloux, Nicolas Pons, Benoît Quinquis, Christine Rouault, Hugo Roume, Joe‐Elie Salem, Nataliya Sokolovska, Nadja B. Søndertoft, Sothea Touch, Sara Vieira‐Silva, Pilar Galán, Jens Juul Holst, Jens Peter Gøtze, Lars Køber, Henrik Vestergaard, Torben F. Hansen, Serge Herçberg, Jean‐Michel Oppert, JENS KVIST NIELSEN, Ivica Letunić, Marc‐Emmanuel Dumas, Michael Stümvoll, Oluf Borbye Pedersen, Peer Bork, S. Dusko Ehrlich, Jean‐Daniel Zucker, Fredrik Bäckhed, Jeroen Raes, Karine Clément · 发表于：Gut · 年份：2022 · DOI：10.1136/gutjnl-2021-325753 · 被引用次数：141 · 研究领域：Biotin and Related Studies、Gut microbiota and health、Vitamin D Research Studies

OBJECTIVES: 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. DESIGN: We 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. RESULTS: Severe 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...