Obesity and the Gut Microbiome

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. A new study 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. This study thus provides a mechanistic linkage between gut commensals and obesity through the overproduction of microbe-derived lipids.

Takeuchi T, Kameyama K, Miyauchi E, Nakanishi Y, Kanaya T, Fujii T, Kato T, Sasaki T, Tachibana N, Negishi H, Matsui M, Ohno H. Fatty acid overproduction by gut commensal microbiota exacerbates obesity. Cell Metab. 2023 Feb 7;35(2):361-375.e9. doi: 10.1016/j.cmet.2022.12.013. Epub 2023 Jan 17. PMID: 36652945.