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

• Published in: Gut Vol. 71; no. 12; pp. 2463 - 2480
• Main Authors: Tremaroli, Valentina, Falony, Gwen, Prifti, Edi, Debédat, Jean, Le Roy, Tiphaine, Nielsen, Trine, Amouyal, Chloé, André, Sébastien, Andreelli, Fabrizio, Blüher, Matthias, Chakaroun, Rima, Chilloux, Julien, Coelho, Luis Pedro, Das, Promi, Fellahi, Soraya, Galleron, Nathalie, Hansen, Tue H, Holmes, Bridget, Ji, Boyang, Le, Phuong, Le Chatelier, Emmanuelle, Lewinter, Christian, Marquet, Florian, Myridakis, Antonis, Pelloux, Veronique, Quinquis, Benoit, Roume, Hugo, Salem, Joe-Elie, Sokolovska, Nataliya, Søndertoft, Nadja B, Touch, Sothea, Vieira-Silva, Sara, Holst, Jens, Gøtze, Jens Peter, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Nielsen, Jens, Letunic, Ivica, Dumas, Marc-Emmanuel, Stumvoll, Michael, Pedersen, Oluf Borbye, Bork, Peer, Zucker, Jean-Daniel, Raes, Jeroen, Clément, Karine, Alili, Rohia, Astrid, Ehm, Galijatovic, Andersson, Barthelemy, Olivier, Berland, Magalie, Bittar, Randa, Blottière, Hervé, Bosquet, Frederic, Boubrit, Rachid, Bourron, Olivier, Camus, Mickael, Cassuto, Dominique, Collet, Jean-Philippe, Doré, Angélique, Engelbrechtsen, Line, Fezeu, Leopold, Fromentin, Sebastien, Giral, Philippe, Graine, Marianne, Hartemann, Agnes, Hartmann, Bolette, Helft, Gerard, Hornbak, Malene, Hulot, Jean-Sebastien, Isnard, Richard, Jørgensen, Niklas Rye, Julienne, Hanna, Justesen, Johanne, Karup, Nikolaj, Kerneis, Mathieu, Køber, Lars, Kozlowski, Ruby, Kuhn, Michael, Lampure, Aurelie, Lejard, Véronique, Lucas-Martini, Lea, Maziers, Nicolas, Medina-Stamminger, Jonathan, Moitinho-Silva, Lucas, Montalescot, Gilles, Moutel, Sandrine, Olanipekun, Michael, Poitou, Christine, Pousset, Francoise, Pouzoulet, Laurence, Schmidt, Sebastien, Silva, Lucas, Silvain, Johanne, Svendstrup, Mathilde, Swartz, Timothy D, Vanduyvenboden, Thierry, Vatier, Camille
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.12.2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adipose tissue; Animals; Antibiotics; Bacteria; Biosynthesis; Biotin; Biotin - pharmacology; Body fat; Body mass index; Body weight gain; Cardiology and Cardiovascular Disease; chromium picolinate; Confidence intervals; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; diet; Endocrinology and Diabetes; Endocrinology and metabolism; Endokrinologi och diabetes; expression; Food and Nutrition; Gastroenterology & Hepatology; Gastrointestinal Microbiome; Gastrointestinal surgery; Genes; Germfree; Glucose; Gut Microbiome; health; High fat diet; Human health and pathology; Humans; Inflammation; intestinal bacteria; Intestinal microflora; Kardiologi och kardiovaskulära sjukdomar; Life Sciences; Mann-Whitney U test; Metabolic disorders; Metabolites; Metagenomics; Mice; Mice, Inbred C57BL; Microbiomes; Microbiota; micronutrients; nutrition; Obesity; Obesity - metabolism; Obesity, Morbid - surgery; Oligosaccharides; Overweight; Phenotypes; Prebiotics; Surgery; Vitamin B Complex - pharmacology; Vitamins; Weight control; France; intestinal bacteria; nutrition; diabetes mellitus; micronutrients; obesity
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2021-325753

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 number NCT02059538.