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Melatonin (MLT)\u00a0is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota\u2010derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota\u2010derived MLT, while administration with MLT could mitigate OP\u2010related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as <jats:italic>Allobaculum<\/jats:italic> and <jats:italic>Parasutterella<\/jats:italic>, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short\u2010chain fatty acids and decreased trimethylamine N\u2010oxide\u2010related metabolites. Importantly, MLT could modulate the dynamic balance of M1\/M2 macrophages, reduce the serum levels of pro\u2010inflammatory cytokines, and restore gut\u2010barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the \u201cgut\u2010bone\u201d axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP.<\/jats:p>","DOI":"10.1111\/jpi.12954","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T10:15:01Z","timestamp":1713176101000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-2874","authenticated-orcid":false,"given":"Yueqi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital Third Military Medical University Chongqing 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