2026-10-08T09:41:51Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32447160 2026-09-29T12:10:14Z category_24640 category_24691 item_type_3 month_year_09_2026

Mesenchymal stromal cells ameliorate experimental PSC alongside gut microbiota remodeling and enhanced vitamin B6 metabolism Yingduo Yu (23996112) Medical biochemistry - amino acids and metabolites Medical bacteriology Gut microbiota <p dir="ltr">Primary sclerosing cholangitis (PSC) is a progressive cholangiopathy tightly linked to gut microbiota dysregulation via the gut-liver axis. While mesenchymal stromal cell (MSC) therapy holds promise for PSC, whether and how the gut microbiota mediates its efficacy remain unknown. Using Mdr2⁻/⁻ mice, we found that human placenta‑derived MSCs significantly alleviated PSC symptoms, reducing serum liver enzymes, inflammatory cytokines, and histopathological scores. Antibiotic‑mediated gut microbiota depletion partially abrogated these protective effects, indicating a microbiota-dependent mechanism. 16S rRNA sequencing revealed that MSC treatment reshaped gut microbial composition, notably enriching the SCFA‑producing genus g_UBA1819 while depleting the disease‑associated genus g_Alistipes. Functional predictions indicated downregulated lipopolysaccharide biosynthesis and upregulated biotin biosynthesis. Untargeted metabolomics identified reduced fecal levels of 4‑Hydroxy‑3‑(3‑methyl‑2‑butenyl)acetophenone and 4‑Hydroxy‑3‑methylbenzaldehyde, with pathway analysis highlighting vitamin B6 metabolism as a key module linked to MSC therapy. Integrative correlation analyses of differential metabolites, gut microbiota, and liver enzymes, combined with in vivo validation, confirmed that microbiota-derived vitamin B6 mediates the hepatoprotective effects of MSCs in PSC. Collectively, our data demonstrate that MSCs exert therapeutic effects in PSC by reprogramming the gut microbiota and subsequently elevating vitamin B6 levels, establishing a novel “MSC–microbiota–vitamin B6” regulatory axis. These findings provide mechanistic insights and potential microbial biomarkers for MSC‑based therapy in PSC.</p> 2026-09-29T12:10:14Z Dataset Dataset 10.6084/m9.figshare.32447160.v2 https://figshare.com/articles/dataset/_b_MSCs_b_b_ameliorate_b_b_PSC_b_b_by_reprogramming_gut_microbiota_to_enhance_microbial_vitamin_B6_biosynthesis_b_/32447160 CC BY 4.0