日本理研综合医学科学中心Hiroshi Ohno团队近期取得重要工作进展，他们研究发现肠道共生微生物群的脂肪酸过度生会产加剧肥胖。相关研究成果2023年1月17日在线发表于《细胞—代谢》杂志上。

据介绍，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，但目前还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产物的作用方面。

研究人员报道了肠镰孢属（Fusimonas intestini），一种毛螺旋菌科的共生物种，在肥胖和高血糖的人类和小鼠中高度定植，产生长链脂肪酸，如elaidate，从而促进饮食诱导的肥胖。高脂肪摄入改变了参与脂质生成的微生物基因的表达，如脂肪酸代谢调节因子fadR。FadR过表达大肠杆菌的单克隆化加剧了代谢表型，表明细菌脂质代谢的变化是疾病进展的原因。从机理上讲，微生物来源的脂肪酸损害了肠上皮的完整性，从而促进了代谢性内毒素血症。

因此，这一研究通过微生物来源脂质的过量产生，提供了肠道共生菌与肥胖之间的机制联系。

附：英文原文

Title: Fatty acid overproduction by gut commensal microbiota exacerbates obesity

Author: Tadashi Takeuchi, Keishi Kameyama, Eiji Miyauchi, Yumiko Nakanishi, Takashi Kanaya, Takayoshi Fujii, Tamotsu Kato, Takaharu Sasaki, Naoko Tachibana, Hiroki Negishi, Misato Matsui, Hiroshi Ohno

Issue&Volume: 2023-01-17

Abstract: Although recent studies have highlighted the impact of gut microbes on the progressionof obesity and its comorbidities, it is not fully understood how these microbes promotethese disorders, especially in terms of the role of microbial metabolites. Here, wereport that Fusimonas intestini, a commensal species of the family Lachnospiraceae, is highly colonized in both humansand mice with obesity and hyperglycemia, produces long-chain fatty acids such as elaidate,and consequently facilitates diet-induced obesity. High fat intake altered the expressionof microbial genes involved in lipid production, such as the fatty acid metabolismregulator fadR. Monocolonization with a FadR-overexpressing Escherichia coli exacerbated the metabolic phenotypes, suggesting that the change in bacterial lipidmetabolism is causally involved in disease progression. Mechanistically, the microbe-derivedfatty acids impaired intestinal epithelial integrity to promote metabolic endotoxemia.Our study thus provides a mechanistic linkage between gut commensals and obesity throughthe overproduction of microbe-derived lipids.

DOI: 10.1016/j.cmet.2022.12.013

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00550-2