{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:53:08Z","timestamp":1773669188995,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"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":"\n Introduction<\/jats:title>\n \n Slow transit constipation (STC) is a chronic disease characterized by delayed intestinal transit and weakened spontaneous contractions of colonic smooth muscle. Current pharmacological treatments are often associated with adverse effects, highlighting the need for safe and more effective therapeutic strategies. This study investigated the potential role of\n Lactobacillus acidophilus<\/jats:italic>\n (\n L. acidophilus<\/jats:italic>\n ) in regulating intestinal motility and alleviating STC, as well as the underlying mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A humanized mouse model was established by intragastric administration of fecal bacterial suspension from STC patients on alternate days, in order to evaluate the effect of\n L. acidophilus<\/jats:italic>\n on constipation. The regulatory effect of\n L. acidophilus<\/jats:italic>\n on intestinal motility was evaluated using defecation parameters. Colon histopathology was assessed by hematoxylin-eosin (H&amp;E) staining. Immunohistochemistry (IHC), RT-qPCR, ELISA, and\n in vitro<\/jats:italic>\n cell experiments were performed to examine the inflammatory cytokine levels and changes in the 5-hydroxytryptamine (5-HT) signaling pathway. In addition, metagenomic sequencing was used to analyze changes in the intestinal microbial community.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The results showed\n L. acidophilus<\/jats:italic>\n treatment significantly enhanced intestinal peristalsis and maintained the intestinal barrier by up-regulating\n Occludin<\/jats:italic>\n expression and down-regulating inflammatory cytokines, including\n TNF-\u03b1<\/jats:italic>\n and\n IL-1\u03b2<\/jats:italic>\n , thereby suppressing inflammatory responses. Both\n in vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n experiments showed that\n L. acidophilus<\/jats:italic>\n affected the synthesis and release of 5-HT by regulating the expression of\n TPH1<\/jats:italic>\n and the mechanosensitive ion channel\n Piezo1<\/jats:italic>\n . Additionally,\n L. acidophilus<\/jats:italic>\n reshaped the intestinal microbial community structure and altered the inter-bacterial interaction network, which was closely associated with improved intestinal motility.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our current research reveals that constipation symptoms by\n L. acidophilus<\/jats:italic>\n through the gut microbiota composition, intestinal barrier, and the 5-HT signaling pathway. These findings provide a strong theoretical basis for the development of\n L. acidophilus<\/jats:italic>\n as a potential therapeutic strategy for the treatment of STC.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fnut.2026.1775405","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:50:47Z","timestamp":1773665447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactobacillus acidophilus alleviates slow transit constipation by modulating 5-HT pathway and gut microbial composition"],"prefix":"10.3389","volume":"13","author":[{"given":"Yunhe","family":"Fan","sequence":"first","affiliation":[{"name":"Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Qin","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayao","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mureed","family":"Abbas","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixia","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiushan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1136\/gutjnl-2019-318747","article-title":"microRNA overexpression in slow transit constipation leads to reduced Na(V)1.5 current and altered smooth muscle contractility","volume":"69","author":"Mazzone","year":"2020","journal-title":"Gut"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1007\/s11274-022-03409-y","article-title":"Lactobacillus rhamnosus GG normalizes gut dysmotility induced by environmental pollutants via affecting serotonin level in zebrafish larvae","volume":"38","author":"Wang","year":"2022","journal-title":"World J Microbiol Biotechnol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"zrab049","DOI":"10.1093\/bjsopen\/zrab049","article-title":"Slow-transit constipation and criteria for colectomy: a cross-sectional study 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Physiol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00441-017-2755-0","article-title":"Mechanosensitive ion channel Piezo1 is expressed in antral G cells of murine stomach","volume":"371","author":"Lang","year":"2018","journal-title":"Cell Tissue Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1105272","DOI":"10.3389\/fcimb.2023.1105272","article-title":"Improvement of loperamide-hydrochloride-induced intestinal motility disturbance by Platycodon grandiflorum polysaccharides through effects on gut microbes and colonic serotonin","volume":"13","author":"Hao","year":"2023","journal-title":"Front Cell Infect 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