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 GwenORCID, Adriouch Solia, Assmann Karen E, Prifti Edi, Aron-Wisnewsky Judith, Debédat JeanORCID, Le Roy TiphaineORCID, Nielsen TrineORCID, Amouyal Chloé, André Sébastien, Andreelli Fabrizio, Blüher Matthias, Chakaroun RimaORCID, Chilloux Julien, Coelho Luis Pedro, Dao Maria Carlota, Das Promi, Fellahi Soraya, Forslund Sofia, Galleron Nathalie, Hansen Tue H, 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, Galan Pilar, Holst Jens, Gøtze Jens Peter, Køber Lars, Vestergaard Henrik, Hansen TorbenORCID, Hercberg Serge, Oppert Jean-Michel, Nielsen Jens, Letunic Ivica, Dumas Marc-EmmanuelORCID, Stumvoll Michael, Pedersen Oluf Borbye, Bork Peer, Ehrlich Stanislav Dusko, Zucker Jean-Daniel, Bäckhed FredrikORCID, Raes Jeroen, Clément KarineORCID,
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.
Funder
Fondation pour la Recherche Médicale Deutsche Forschungsgemeinschaft Seventh Framework Program Leducq Foundation Sorbonne University
Cited by
71 articles.
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