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Here, we found that high\u2010fat diet promoted the lipid accumulation and intestinal microbiota dysbiosis in mice, while oral melatonin supplementation alleviated the lipid accumulation and reversed gut microbiota dysbiosis, including the diversity of intestinal microbiota, relative abundances of <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Alistipes<\/jats:italic>, and functional profiling of microbial communities, such as energy metabolism, lipid metabolism, and carbohydrate metabolism. Interestingly, melatonin failed to alleviate the high\u2010fat\u2010induced lipid accumulation in antibiotic\u2010treated mice; however, microbiota transplantation from melatonin\u2010treated mice alleviated high\u2010fat diet\u2010induced lipid metabolic disorders. Notably, short\u2010chain fatty acids were decreased in high\u2010fat diet\u2010fed mice, while melatonin treatment improved the production of acetic acid. Correlation analysis found a marked correlation between production of acetic acid and relative abundances of <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Alistipes<\/jats:italic>. Importantly, sodium acetate treatment also alleviated high\u2010fat diet\u2010induced lipid metabolic disorders. Taken together, our results suggest that melatonin improves lipid metabolism in high\u2010fat diet\u2010fed mice, and the potential mechanisms may be associated with reprogramming gut microbiota, especially, <jats:italic>Bacteroides<\/jats:italic> and <jats:italic>Alistipes<\/jats:italic>\u2010mediated acetic acid production. Future studies are needed for patients with metabolic syndrome to fully understand melatonin\u2019s effects on body weight and lipid profiles and the potential mechanism of gut microbiota.<\/jats:p>","DOI":"10.1111\/jpi.12524","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T13:07:56Z","timestamp":1537362476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":368,"title":["Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high\u2010fat diet\u2010fed mice"],"prefix":"10.1111","volume":"65","author":[{"given":"Jie","family":"Yin","sequence":"first","affiliation":[{"name":"Key Laboratory of Agro\u2010ecological Processes in Subtropical Region, Institute of Subtropical Agriculture Chinese Academy of Sciences Changsha China"},{"name":"Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Changsha China"},{"name":"Guangdong Provincial Key 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