{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:36:33Z","timestamp":1784925393634,"version":"3.55.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Constipation is a prevalent and recurrent gastrointestinal disorder causing significant discomfort. However, current treatments often prove ineffective. Previous research indicates that the postbiotic derived from a combination of hawthorn and probiotics can alleviate constipation. This study aimed to investigate its mechanisms using loperamide-induced constipation in aged KM mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Constipated mice were divided into groups receiving 10% lactulose (Y), hawthorn extract (S), probiotics (F), and the postbiotic of hawthorn-probiotic (FS). UPLC\u2013MS metabolomics identified constituents of F, S, and FS. Network pharmacological analysis identified targets affected by FS. RT-qPCR assessed target expression in mouse colons, along with IL-6 and IL-17A levels. Molecular docking with AutoDock Tools1.5.6 evaluated interactions between FS components and targets. ex vivo colonic organ culture and RT-qPCR assessed target changes. Molecular dynamics analysis further scrutinized interactions. Targeted metabolomics measured short-chain fatty acid levels in mouse stool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>UPLC\u2013MS metabolomics revealed distinct profiles for F, S, and FS, with FS showing decreased toxic substances and increased beneficial ones compared to S. Network pharmacology identified 20 cross-targets of FS in constipation. RT-qPCR showed decreased NR1I2 and SULT1A1 and increased GLP-2r in FS-treated mice. Inflammatory cytokines IL-6 and IL-17A were also reduced. ex vivo colonic organ culture and molecular docking identified effective combinations such as TNF-Baicalin and AQP3-Quinacridone. RMSD, RMSF, and RG analyses indicated favorable interactions between small molecules and targets. Targeted metabolomics revealed differing short-chain fatty acid contents in feces among groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The postbiotic of hawthorn-probiotic alleviates constipation by regulating intestinal water and sodium metabolism, maintaining the intestinal barrier and gut flora, promoting epithelial cell proliferation, reducing inflammatory responses, and improving short-chain fatty acid metabolism.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1498004","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T05:21:28Z","timestamp":1739856088000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Multi-omics revealed that the postbiotic of hawthorn-probiotic alleviated constipation caused by loperamide in elderly mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Yu","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.bpg.2009.09.001","article-title":"Constipation in old age","volume":"23","author":"Gallagher","year":"2009","journal-title":"Best Pract Res Clin 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