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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\u2010spectrum antibiotic cocktail (ABX) for 10\u2009days. The treatment significantly reduced gut microbes and disrupted the metabolism of arginine and tryptophan. Consequently, ABX\u2010treated 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\u2010suppressing hormone cholecystokinin in the blood were significantly elevated. In the second phase, control mice were maintained, while the ABX\u2010treated mice received saline, probiotics, and short\u2010chain fatty acids (SCFAs) for an additional 10\u2009days 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\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    and\n                    <jats:italic>Bacteroides<\/jats:italic>\n                    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\u2010treated mice had the highest feed intake and NPY expression. Our findings indicate that gut microbes, especially\n                    <jats:italic>Akkermansia<\/jats:italic>\n                    , regulate arginine and tryptophan metabolism, thereby influencing appetite through the microbe\u2010gut\u2010brain axis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401360r","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T05:55:13Z","timestamp":1724046913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Microbiome and metabolome analyses indicate variations in the gut microbiota that disrupt regulation of appetite"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-8983","authenticated-orcid":false,"given":"Renli","family":"Qi","sequence":"first","affiliation":[{"name":"Chongqing Academy of Animal Science  Chongqing 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