A microbial metabolite produced by Enterococcus faecium activates Ffar2 to mediate the beneficial effects of dietary fiber on obesity
Gut microbiota is a target for the prevention and treatment of obesity and related metabolic diseases. Dietary interventions such as fiber have been shown to alleviate obesity through gut microbiota and its derivatives. Here, we screened a candidate strain of dietary fiber for obesity prevention, Enterococcus faecium (E. faecium), from datasets and isolated it from human and mouse feces. Supplementation with E. faecium suppressed adipocyte enlargement, dyslipidemia, and hepatic steatosis in obese mice. Then, we incubated four types of dietary fibers with the feces of 10 donors to screen the dietary fibers that promoted the growth of E. faecium. Among them, konjac polysaccharides (KP) have the best effect. In vivo validation experiments also showed that dietary fiber KP, which enriched E. faecium, has the benefit of preventing obesity. Mechanistically, E. faecium-derived leucic acid was a key effector molecule that prevented the disorder of glucose and lipid metabolism in obese mice by activating free fatty acid receptor 2 (Ffar2). E. faecium or leucic acid was protective against obesity in mice. These findings explained the unique mechanism by which E. faecium regulated host obesity, revealing that dietary fiber could enrich gut microbiota members to generate beneficial metabolites to alleviate obesity.