Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France.
Integrative Phenomics, Paris, France.
Gut. 2022 Dec;71(12):2463-2480. doi: 10.1136/gutjnl-2021-325753. Epub 2022 Jan 11.
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.
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.
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 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.
Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.
NCT02059538.
肠道微生物群是肥胖和 2 型糖尿病的关键组成部分，但这一相互作用的机制和代谢物仍不清楚。我们在 MetaCardis 队列中检查了健康代谢状态和肥胖症及 2 型糖尿病最严重状态下人类肠道微生物组的功能组成。我们专注于 B 族维生素和 B7/B8 生物素在调节宿主代谢状态中的作用，因为这些维生素既影响微生物功能，也影响宿主代谢和炎症。
我们对 MetaCardis 队列中的 1545 名受试者和不同的小鼠实验进行了宏基因组分析，包括无菌和抗生素处理动物、粪便微生物群转移、减肥手术以及在小鼠中补充生物素和益生元。
严重肥胖与细菌生物素生产者和转运体的绝对缺乏有关，其丰度与宿主代谢和炎症表型相关。我们发现严重肥胖症患者循环生物素水平较低，且人脂肪组织中与生物素相关的基因表达发生改变。在小鼠中，抗生素对肠道微生物群的缺失或耗尽证实了微生物对宿主生物素水平的贡献。减肥手术可改善代谢和炎症，与宿主生物素水平的细菌生物素生产者增加和改善相关，且在人和小鼠中均如此。最后，用果寡糖和生物素补充高脂肪饮食喂养的小鼠不仅改善了微生物组的多样性，还改善了细菌生物素和 B 族维生素的潜在产量，同时限制了体重增加和血糖恶化。
联合生物素和益生元补充的策略可能有助于预防严重肥胖症代谢状态的恶化。
NCT02059538。
