Microbiome and metabolome analyses indicate variations in the gut microbiota that disrupt regulation of appetite

Abstract The mechanism connecting gut microbiota to appetite regulation is not yet fully understood. This study identifies specific microbial community and metabolites that may influence appetite regulation. In the initial phase of the study, mice were administered a broad‐spectrum antibiotic cocktail (ABX) for 10 days. The treatment significantly reduced gut microbes and disrupted the metabolism of arginine and tryptophan. Consequently, ABX‐treated mice demonstrated a notable reduction in feed consumption. The hypothalamic expression levels of CART and POMC, two key anorexigenic factors, were significantly increased, while orexigenic factors, such as NPY and AGRP, were decreased. Notably, the levels of appetite‐suppressing hormone cholecystokinin in the blood were significantly elevated. In the second phase, control mice were maintained, while the ABX‐treated mice received saline, probiotics, and short‐chain fatty acids (SCFAs) for an additional 10 days to restore their gut microbiota. The microbiota reconstructed by probiotic and SCFA treatments were quite similar, while microbiota of the naturally recovering mice demonstrated greater resemblance to that of the control mice. Notably, the abundance of Akkermansia and Bacteroides genera significantly increased in the reconstructed microbiota. Moreover, microbiota reconstruction corrected the disrupted arginine and tryptophan metabolism and the abnormal peripheral hormone levels caused by ABX treatment. Among the groups, SCFA‐treated mice had the highest feed intake and NPY expression. Our findings indicate that gut microbes, especially Akkermansia , regulate arginine and tryptophan metabolism, thereby influencing appetite through the microbe‐gut‐brain axis.