Gut microbiota mediates the anti-obesity effect of intermittent fasting by inhibiting intestinal lipid absorption

The prevention and treatment of obesity have been one of the most difficult problems in the world. Intermittent fasting (IF) has received wide attention as an effective diet strategy. Existing studies have shown that IF could improve obesity and diabetes-related metabolic disorders. Here, we show that IF can change the composition and metabolic function of intestinal microbes, and reduce lipid absorption by inhibiting PI3K/AKT signaling pathway, with the participation of arginine. Arginine concentration in feces of fasted mice is inversely correlated with Akkermansia muciniphila abundance. Antibiotic-induced clearance of intestinal microbiota greatly inhibits the effect of IF. Furthermore, the colonization test of Akkermansia muciniphila again activates the browning of white adipose tissue and restores the improvement of metabolism to alleviate obesity. These phenomena indicate that every-other-day fasting regimen inhibits intestinal lipid absorption and promotes the browning of white adipose tissue in mice to ameliorate the risk of obesity and metabolic disorders through the microbial flora-metabolite-fat signaling axis. And the above results demonstrate new directions for the treatment of obesity and other metabolic disorders.