PhD Student Sorbonne Université/INSERM Paris, Ile-de-France, France
Lise Voland (Sorbonne Université/INSERM)| Jean Debédat (Sorbonne Université/INSERM)| Eugeni Belda (Integrative Phenomics)| Camille Gamblin (Sorbonne Université/INSERM)| the Metacardis Consortium (Metacardis)| Tiphaine Le Roy (Sorbonne Université/INSERM)| Karine Clément (Sorbonne Université/INSERM, Sorbonne Université/INSERM)
Severe obesity is associated with major tissue alterations and systemic low-grade inflammation as well as with modifications of gut microbiota composition and functionality. Yet, there is increasing evidence revealing that the gut microbiota could influence metabolic health via the production of many microbiota-derived metabolites which contribute to complex interorgan dialogs. Vitamins and more specifically B vitamins have been neglected in this context. Amongst them, Vitamin B7/biotin plays an important role in many physiological functions including carbohydrate and lipid metabolism. Although, biotin supplementation is suggested to improve glucose metabolism in type 2 diabetes (T2D), this vitamin has not been widely studied in metabolic disorders including subjects with severe obesity. We, here, investigated both the bacterial and host metabolism of biotin, using large scale data from the European cohort Metacardis and different murine models. Examining metagenomic data of gut microbiota from human with worsening stages of obesity and diet-induced obesity in mice revealed deficiency in biotin microbial production and transport. This altered gut microbial metabolism was associated with metabolic and inflammatory deterioration in the human host. In the same subjects with severe obesity, we found suboptimal circulating levels of biotin and altered expression of biotin-associated genes in adipose tissue. Then, we demonstrated the contribution of the gut microbiota to the host circulating biotin by a series of experiments performed in Germ-free animals, antibiotic-treated mice and after gut microbiota transfer (from human to mice). Furthermore, we studied gut microbiota biotin metabolism in the context of obesity management. First, bariatric surgery, which is known to improve metabolism and inflammation and to induce changes in gut microbiota composition, was associated with increased bacterial biotin producers together with improved systemic biotin in mice and humans. Second, the concomitant management of biotin status and dysbiosis in the context of installed obesity in mice was explored. The oral supplementation of mice with installed obesity with both biotin and a prebiotic fructoligosaccharide (FOS) led to limited weight gain and glycemic deterioration compared to animals with no supplementation. The mice supplemented by FOS and biotin also improved their bacterial biotin metabolism better than the other groups. Altogether, these results suggest the importance of biotin, and more generally B vitamins, in severe obesity and pave the way for future clinical investigation of biotin and prebiotic administration in humans to prevent obesity from transitioning to a more severe metabolic state.