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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. [Display omitted] • Fusimonas intestini (FI), a commensal species, exacerbates diet-induced obesity • FI abundantly produces long-chain fatty acids such as elaidate • FI and its fatty acid metabolites impair gut integrity • Fatty acid overproduction by a model bacterial strain aggravates an obese phenotype The mechanistic linkage between obesity and gut microbiota remains elusive. Takeuchi et al. report that a member of commensal microbiota prevalent in individuals with diabetes and obesity produces abundant long-chain fatty acids such as elaidate, a trans -unsaturated fatty acid, and aggravates diet-induced obesity through the impairment of gut integrity. [ABSTRACT FROM AUTHOR]

Complex interactions between immune cells are an important component in the induction of obesity. Here, we show that Il2rg − / − Rag2 − / − mice lacking all lymphocytes are resistant to diet-induced obesity. Transplantation of bone marrow cells from Rag2 − / − mice, which lack only acquired immune cells, into Il2rg − / − Rag2 − / − mice abolishes this resistance, indicating a role for innate lymphoid cells (ILCs) in this process. Mice lacking ILC2 or ILC3 cells, but not natural killer cells, are resistant to obesity. Adoptive transfer of naive ILC2s isolated from the small intestine (SI), but not ILC2s from white adipose tissue (WAT), restores the induction of diet-induced obesity in Il2rg − / − Rag2 − / − mice. Analysis of transcriptional differences reveals that SI-ILC2s express higher levels of IL-2 than do WAT-ILC2s and that blockade of IL-2 signaling impairs weight gain and reduces the populations of ILC2s and ILC3s in the SI, suggesting a role for the IL-2/ILC2/3 axis in the induction of obesity. • Innate lymphoid cells are involved in the induction of diet-induced obesity • ILC2s and ILC3s but not ILC1/NK/exILC3 cells are involved in the induction of obesity • SI-ILC2s but not WAT-ILC2s are involved in the induction of obesity • IL-2 is critical for the maintenance and function of SI-ILC2s and ILC3s Innate lymphoid cells (ILCs) are recently identified lymphocyte populations characterized by the lack of antigen-specific receptors. Sasaki et al. demonstrate the involvement of ILCs in the induction of diet-induced obesity. Specifically, they show that small intestinal ILC2s, but not white adipose tissue ILC2s, are involved in the induction of obesity. [ABSTRACT FROM AUTHOR]