Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
Institute of Food Sciences and Technologies, Ajinomoto Co., Inc., Kawasaki 210-8681, Japan.
Cell Metab. 2023 Feb 7;35(2):361-375.e9. doi: 10.1016/j.cmet.2022.12.013. Epub 2023 Jan 17.
Although recent studies have highlighted the impact of gut microbes on the progression of obesity and its comorbidities, it is not fully understood how these microbes promote these disorders, especially in terms of the role of microbial metabolites. Here, we report that Fusimonas intestini, a commensal species of the family Lachnospiraceae, is highly colonized in both humans and mice with obesity and hyperglycemia, produces long-chain fatty acids such as elaidate, and consequently facilitates diet-induced obesity. High fat intake altered the expression of microbial genes involved in lipid production, such as the fatty acid metabolism regulator fadR. Monocolonization with a FadR-overexpressing Escherichia coli exacerbated the metabolic phenotypes, suggesting that the change in bacterial lipid metabolism is causally involved in disease progression. Mechanistically, the microbe-derived fatty acids impaired intestinal epithelial integrity to promote metabolic endotoxemia. Our study thus provides a mechanistic linkage between gut commensals and obesity through the overproduction of microbe-derived lipids.
尽管最近的研究强调了肠道微生物对肥胖及其合并症进展的影响，但人们并不完全了解这些微生物如何促进这些疾病，特别是在微生物代谢物的作用方面。在这里，我们报告说，梭菌属肠道内细菌（Fusimonas intestini）是厚壁菌门lachnospiraceae 家族的一种共生种，在肥胖和高血糖的人类和小鼠中高度定植，产生油酸等长链脂肪酸，并因此促进了饮食诱导的肥胖。高脂肪摄入改变了与脂质产生相关的微生物基因的表达，如脂肪酸代谢调节剂 fadR。用过表达 fadR 的大肠杆菌单定植加剧了代谢表型，表明细菌脂质代谢的变化与疾病进展有因果关系。从机制上讲，微生物衍生的脂肪酸破坏了肠道上皮细胞的完整性，从而促进了代谢性内毒素血症。因此，我们的研究通过微生物衍生脂质的过度产生，为肠道共生菌与肥胖之间提供了一种机制联系。
