In vitro screening of synbiotics based on a four-strain probiotic blend and their therapeutic potential for ulcerative colitis

Abstract

This study explores the therapeutic effects of synbiotics on ulcerative colitis (UC) using an in vitro fermentation model and a Dextran Sulfate Sodium (DSS)-induced UC mouse model. We assessed the impact of synbiotics on probiotic proliferation, short-chain fatty acid (SCFA) production, metabolic regulation, and intestinal barrier function. Fructooligosaccharide (FOS) and Inulin (INU) significantly promoted probiotic growth and increased SCFA production, especially acetate, propionate, butyrate, and isobutyrate (p < 0.01). Metabolomics analysis revealed compound probiotics (CP)+FOS and CP+INU significantly modulated probiotic metabolic activity (p < 0.05), affecting metabolites and related pathways. In the DSS-induced UC mouse model, the combination of CP+FOS and CP+INU alleviated UC symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while increasing spleen index. Histological analysis showed synbiotics preserved colonic crypts, reduced inflammatory cell infiltration, and enhanced intestinal barrier function, with the CP+FOS group showing the most pronounced effects. Immunohistochemistry revealed restored expression of tight junction proteins (Claudin-1, Occludin, ZO-1), further supporting intestinal barrier protection. The synbiotic combination modulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and increased anti-inflammatory IL-10 (p < 0.01). SCFA analysis showed significant increases in all measured SCFAs (p < 0.01). Correlation analysis indicated strong positive associations between SCFAs, body weight, colon length, and IL-10. In conclusion, the synbiotic combination of FOS and INU shows significant potential in alleviating UC symptoms, repairing the intestinal barrier, and modulating inflammation, supporting its potential as an adjunct or alternative UC therapy.