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

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.

Tiny contributors to severe obesity inside the gut

“…11 Overall, the results point to the role played by the low abundance of microbial genes capable of supplying biotin to the host, which is compatible with the suboptimal biotin status and hallmarks of metabolic dysfunction and inflammation detected in the affected subjects. 11 The human host's primary source of biotin comes from the diet but gut bacteria can also synthetise biotin and, thus, presumably contribute to the host's biotin status. Biotin acts as enzyme cofactor and, for example, participates in the carboxylation of pyruvate to oxaloacetate and triggers fatty-acid biosynthesis, contributing to adipose tissue and whole body metabolism.…”

“…3 Consistent with the first findings in subjects with severe obesity, Belda et al also showed that bariatric surgery, in both humans and animals, led to increased microbial biotin producers and an improved host biotin status. 11 Moreover, the authors have made progress in the consolidation of their hypothesis by carrying out an animal study of high-fat diet (HFD)-induced obesity, which reduced the microbial counts and biotin gene potential as well as the host's biotin levels. However, this study did not prove causality as the effects on biotin could be due to either diet or dietinduced dysbiosis, or indeed both.…”

“…In Gut , Belda et al take on the challenge of identifying the mechanisms through which alterations in the gut microbiota can be functionally involved in severe obesity, applying a translational research approach and validating the findings in different study models 11. Overall, the results point to the role played by the low abundance of microbial genes capable of supplying biotin to the host, which is compatible with the suboptimal biotin status and hallmarks of metabolic dysfunction and inflammation detected in the affected subjects 11…”

Gut Microbiota, Macrophages and Diet: An Intriguing New Triangle in Intestinal Fibrosis

“…Therefore, a dysfunctional microbiota could propagate impaired vitamin synthesis and metabolism and could participate in the pathogenesis of several inflammatory diseases [ 100 ]. For example, severe obesity is associated with gut dysbiosis and a recent study by Clément et al, has demonstrated the link between gut microbiota, vitamin B, and metabolic response [ 101 ]. Indeed, patients with severe obesity exhibited a deficiency in bacteria involved in the production and/or transport of biotin, leading to reduced circulating biotin levels, and the abundance of these bacterial species are correlated with host metabolism and inflammatory response [ 101 ].…”

“…For example, severe obesity is associated with gut dysbiosis and a recent study by Clément et al, has demonstrated the link between gut microbiota, vitamin B, and metabolic response [ 101 ]. Indeed, patients with severe obesity exhibited a deficiency in bacteria involved in the production and/or transport of biotin, leading to reduced circulating biotin levels, and the abundance of these bacterial species are correlated with host metabolism and inflammatory response [ 101 ]. The role of fat wrapping of the intestine in response to bacterial translocation through micro-penetrating disease with involvement of macrophages and adipocytes has been recently highlighted in human disease and animal models [ 50 ].…”