Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalization of gut microbiota

Abstract Background Crohn's disease (CD) is a chronic nonspecific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD and therefore it is of great significance to find new treatment strategy for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach, However，the mechanism of MSC alleviating CD and how MSC affects gut microbes is still unclear and needs to be further elucidated. MethodsWe used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice, and analyzed the microbiota in the fecal samples, which come from the control group, the TNBS group and the TNBS+MSC group with fecal 16S rDNA sequencing. Subsequent analysis of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was subsequently performed from 16S rRNA gene sequences to infer gut microbiome functions. ResultsMSCs treatment improved the TNBS-induced colitis by increasing survival rates, relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS+MSC group and controls. MSC alleviated the increased activities of sulfur and riboflavin metabolism.Meanwhile some metabolisms such as biosynthesis of amino acids，lysine biosynthesis, sphingolipid metabolism，secondary bile acid biosynthesis were decreased in the TNBS group when compared with the control group and the TNBS+MSC group.ConclusionsMSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to a normal situation as the control group.