biostudies-literatureDong XTianjin Health Traditional Chinese Medicine Research ProjectTianjin Health Research ProjectNational Natural Science Foundation of China205https://www.ebi.ac.uk/biostudies/studies/S-EPMC12903243biostudies-literatureUnknown24(1)<h4>Background</h4>Functional constipation (FC) is a prevalent gastrointestinal disorder marked by impaired intestinal motility, affecting millions worldwide and significantly diminishing quality of life. Current therapeutic strategies provide only transient symptom relief and fail to restore colonic motor function. This study aims to explore the causal role of gut microbiota in FC, focusing on the mechanisms by which Roseburia intestinalis (RI) and its metabolite inosine improve intestinal motility.<h4>Methods</h4>To identify protective gut taxa, we first performed bidirectional Mendelian randomization (MR) integrated with 16S rRNA sequencing on fecal samples from 30 FC patients and 30 healthy controls. Loperamide-induced constipation mouse models evaluated RI gavage effects on motility iJournal of translational medicineRoseburia intestinalis-derived inosine improves intestinal motility by activating TGF-β1/p-Smad3/Transgelin signaling axis.PMC129032432025185TJWJ2024XK004823705458217032098Liu HSun MJiang KRuan HDong XWang BChen MZhang HZhong WfalseRoseburia intestinalis-derived inosine improves intestinal motility by activating TGF-β1/p-Smad3/Transgelin signaling axis.<h4>Background</h4>Functional constipation (FC) is a prevalent gastrointestinal disorder marked by impaired intestinal motility, affecting millions worldwide and significantly diminishing quality of life. Current therapeutic strategies provide only transient symptom relief and fail to restore colonic motor function. This study aims to explore the causal role of gut microbiota in FC, focusing on the mechanisms by which Roseburia intestinalis (RI) and its metabolite inosine improve intestinal motility.<h4>Methods</h4>To identify protective gut taxa, we first performed bidirectional Mendelian randomization (MR) integrated with 16S rRNA sequencing on fecal samples from 30 FC patients and 30 healthy controls. Loperamide-induced constipation mouse models evaluated RI gavage effects on motility i2025-01-01T00:00:00Z2025 Dec2026-07-15T15:34:48.467Z2026-07-06T03:10:34.326ZS-EPMC129032434142203510.1186/s12967-025-07366-6