Comparison of the effects of sulfasalazine and synbiotic treatments on the gut microbiota in a rat model of ulcerative colitis

Ulcerative colitis (UC) is one of the most common forms of inflammatory bowel disease, characterized by chronic relapsing inflammation of the colon and a significant reduction in patients' quality of life. Although current therapeutic agents such as sulfasalazine effectively suppress inflammation, their long-term efficacy remains limited and adverse effects are frequent. Thus, microbiota-targeted approaches have emerged as promising alternatives. This study aimed to compare the therapeutic effects of sulfasalazine and a synbiotic combination (Bacillus coagulans + chitosan oligosaccharide) in a DSS-induced experimental UC model, focusing on microbiota composition, histopathological findings, and immunological parameters. Ulcerative colitis was induced in rats using dextran sodium sulfate (DSS), followed by treatment with either sulfasalazine or the synbiotic formulation. Therapeutic outcomes were evaluated through changes in body weight, histopathological scoring, and microbiota analysis based on 16S rRNA sequencing. Microbial diversity (alpha and beta diversity indices), dysbiosis markers, and mucosal integrity parameters were assessed in a comparative manner. The DSS group exhibited a marked reduction in microbial diversity, an increase in potentially pathogenic bacteria, and significant impairment of mucosal integrity. While sulfasalazine treatment effectively suppressed inflammatory responses, synbiotic supplementation particularly promoted restoration of microbial diversity, enrichment of butyrate-producing taxa, and improvement in mucosal healing. Both treatments acted through distinct mechanisms: sulfasalazine primarily through immunosuppressive effects, and the synbiotic via modulation of the gut microbiota and reinforcement of barrier functions. This study provides a comparative evaluation of a conventional pharmacological agent (sulfasalazine) and a microbiota-based synbiotic therapy in UC. The findings highlight that synbiotic intervention offers promising potential by restoring microbial balance and enhancing mucosal integrity. These results support the translational value of probiotic–prebiotic combinations as complementary or alternative therapeutic strategies in ulcerative colitis management. Keywords: Ulcerative colitis, Microbiota, Sulfasalazine, Bacillus coagulans, Synbiotic