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TMP or pioglitazone was administered during the final 3\u00a0weeks. Hepatic injury, intestinal barrier integrity, gut microbiota, bile acids (BAs), short\u2010chain fatty acids (SCFAs) and faecal metabolomics were assessed using histology, biochemical assays, RT\u2010qPCR, western blotting, 16S rDNA sequencing and metabolomics. Faecal microbiota transplantation (FMT) and lipopolysaccharide (LPS)\u2013stimulated Caco\u20102 cells were used to evaluate microbiota\u2010dependent and direct intestinal protective effects of TMP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>TMP alleviated hepatic steatosis, inflammation and fibrosis in MCD\u2010fed mice. TMP decreased hepatic macrophage infiltration and inflammatory cytokines, including TNF\u2010\u03b1, IL\u20101\u03b2 and IL\u20106. In the intestine, TMP restored epithelial structure, increased faecal sIgA, reduced serum LPS, D\u2010lactate, zonulin and TNF\u2010\u03b1 and up\u2010regulated Claudin\u20101, ZO\u20101 and Occludin. TMP improved gut microbial diversity, suppressed proinflammatory bacteria and enriched beneficial taxa. FMT from TMP\u2010treated donors partially reproduced the hepatoprotective effects in recipient mice. TMP further restored BA and SCFA homeostasis, regulated the FXR\/FGF15\/CYP7A1 axis and remodelled faecal metabolic profiles associated with lipid peroxidation and inflammation. In Caco\u20102 cells, TMP attenuated LPS\u2010induced IL\u20101\u03b2 and IL\u20106 expression and restored Occludin expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>TMP exerts protective effects against MCD diet\u2013induced MASH by improving hepatic pathology and restoring gut\u2013liver axis homeostasis, including intestinal barrier integrity, gut microbiota composition, BA and SCFA metabolism and faecal metabolic balance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70640","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:28:04Z","timestamp":1789108084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tetramethylpyrazine ameliorates metabolic dysfunction\u2013associated steatohepatitis by modulating gut microbiota 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