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Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of<jats:italic>Limosilactobacillus reuteri<\/jats:italic>(<jats:italic>L. reuteri<\/jats:italic>) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)\/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following<jats:italic>L. reuteri<\/jats:italic>administration to protect darkness rats against dyslipidemia. Notably,<jats:italic>L. reuteri<\/jats:italic>intervention resulted in the decrease of<jats:italic>Clostridium sensu stricto 1<\/jats:italic>and<jats:italic>Ruminococcaceae UCG-010<\/jats:italic>as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as<jats:italic>L. reuteri<\/jats:italic>to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of<jats:italic>L. reuteri<\/jats:italic>in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that<jats:italic>L. reuteri<\/jats:italic>could serve for circadian disruption-associated dyslipidemia. Manipulation of<jats:italic>L. reuteri<\/jats:italic>\u2013capric acid\u2013GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.<\/jats:p>","DOI":"10.1038\/s41522-023-00415-2","type":"journal-article","created":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T07:02:12Z","timestamp":1688799732000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-0902","authenticated-orcid":false,"given":"Shang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongshuang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luwei","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Yee","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6637-6631","authenticated-orcid":false,"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-3390","authenticated-orcid":false,"given":"Yanzhi","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,8]]},"reference":[{"key":"415_CR1","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1210\/er.2015-1018","volume":"36","author":"DA Dumesic","year":"2015","unstructured":"Dumesic, D. 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