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TLR4\/MyD88\/NF-\u03baB pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult male Sprague-Dawley (SD) rats were used to establish an IBS-D model through a combination of chronic and acute stress. The rats were randomly divided into four groups: healthy control (HC), IBS-D, IBS-D\u2009+\u2009melatonin 5\u00a0mg\/kg (M-L), and IBS-D\u2009+\u2009melatonin 10\u00a0mg\/kg (M-H), with six rats in each group. Visceral sensitivity was assessed using the abdominal withdrawal reflex (AWR). The expression levels of tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6) in colon tissue were measured using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunohistochemistry were employed to detect the expression of TLR4, MyD88, and NF-\u03baB proteins in colon tissue. Additionally, 16\u00a0S rRNA sequencing was used to analyze the composition of the intestinal microbiota.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to the HC group, the IBS-D group exhibited colonic inflammatory injury, increased AWR scores, elevated levels of TNF-\u03b1, IL-6, TLR4, MyD88, and NF-\u03baB in the colon, and altered intestinal microbiota composition. Melatonin treatment reduced colonic inflammatory injury, decreased AWR scores, and lowered the levels of TNF-\u03b1, IL-6, TLR4, MyD88, and NF-\u03baB in a dose-dependent manner. The intestinal microbiota composition in melatonin-treated groups showed a trend towards that of the HC group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Melatonin improved diarrhea and visceral hypersensitivity in IBS-D rats, potentially through the modulation of the TLR4\/MyD88\/NF-\u03baB pathway and partial restoration of the intestinal microbiota.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12876-025-04203-4","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T13:00:21Z","timestamp":1760014821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Melatonin alleviates diarrhea and visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome by modulating of the TLR4\/MyD88\/NF-\u03baB pathway"],"prefix":"10.1186","volume":"25","author":[{"given":"Zuohui","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"4203_CR1","doi-asserted-by":"crossref","unstructured":"Grayson M. 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