{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:18:29Z","timestamp":1791260309790,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1300100"],"award-info":[{"award-number":["2022YFD1300100"]}]},{"name":"China Agriculture Research System","award":["CARS-40-K03"],"award-info":[{"award-number":["CARS-40-K03"]}]},{"award":["CARS-40-K03"],"award-info":[{"award-number":["CARS-40-K03"]}],"id":[{"id":"https:\/\/ror.org\/03p5eky76","id-type":"ROR","asserted-by":"publisher"}]},{"name":"SAAS Program for Excellent Research Team","award":["2022-021"],"award-info":[{"award-number":["2022-021"]}]},{"DOI":"10.13039\/501100007198","name":"Shanghai Academy of Agricultural Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007198","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04ejmmq75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Clutch persistence, defined as the ability to sustain consecutive egg-laying cycles, is a pivotal determinant of profitability in the poultry industry, particularly for aging laying hens (\u226565 weeks). However, the molecular mechanisms governing this trait remain elusive, largely due to the traditional \u201covary-centric\u201d paradigm that overlooks systemic regulation by the gut microbiota. To address this knowledge gap, the present study aimed to dissect the comprehensive regulatory network governing clutch persistence using integrated multi-omics analyses. A total of 20 sixty-five-week-old Rhode Island Red (RIR) laying hens with cumulative egg production exceeding 300 eggs but distinct clutch persistence were stratified into a high-clutch persistence group (HCP, \u226525 clutches, n = 10) and a low-clutch persistence group (LCPLCP, \u226415 clutches, n = 10). Multi-omics profiling, including ovarian transcriptomics, proteomics, and metabolomics; serum metabolomics; and cecal microbiota 16S rRNA sequencing was performed. Data integration and association mining were conducted via Spearman correlation analysis with stringent thresholds (r &gt; 0.6, p &lt; 0.01). Integrated analyses revealed a \u201cgut\u2013ovary axis\u201d regulatory model mediated by a lipid mediator network, operating through a three-tiered mechanism: (1) Gut Initiation: The HCP group exhibited enriched cecal \u03b3-Proteobacteria, which promoted biosynthesis of lipid precursors. (2) Serum Transport: Key serum lipid mediators, most notably LysoPC (22:6) (VIP = 4.5) and cholesterol ester CE (20:4), served as critical carriers transducing gut-derived signals to the ovary. (3) Ovarian Execution: These lipid signals activated a core ovarian metabolic pathway centered on the PLA2G6-ALOX15B-AGPAT3 axis, which coordinated follicular development and ovulation by supplying steroid hormone synthesis substrates, exerting anti-inflammatory effects, and stabilizing membrane structures. Collectively, this study demonstrates that gut microbiota modulates clutch persistence in aging laying hens via lipid mediators, orchestrating a systemic \u201cgut\u2013serum\u2013ovary\u201d regulatory cascade. These findings provide a novel molecular framework for extending the economic egg-laying cycle through the targeted manipulation of intestinal microbiota or serum lipid metabolism.<\/jats:p>","DOI":"10.3390\/biom16050708","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:46:18Z","timestamp":1779381978000},"page":"708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gut-Derived Lipid Mediators Orchestrate Ovarian Metabolic Homeostasis and Clutch Persistence in Aging Laying Hens via the PLA2G6-ALOX15B-AGPAT3 Axis"],"prefix":"10.3390","volume":"16","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Meng","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6425-7786","authenticated-orcid":false,"given":"Yanyan","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105210","DOI":"10.1016\/j.psj.2025.105210","article-title":"Synergistic transcriptomic and metabolomic analyses in Zi geese ovaries with different clutch lengths","volume":"104","author":"Liu","year":"2025","journal-title":"Poult. 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