Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 32 44 Yanlin Qiao Digestive Surgery, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Xiang Gao Digestive Surgery, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China 2024 12 23 2025 08 01 This study examines the interaction between the microbiota and the immune system in diseases of the gastrointestinal tract, with a special emphasis on the synergistic use of pharmacological agents. This was a retrospective, observational study of 100 patients with moderate to severe gastrointestinal disorders, including irritable bowel syndrome and inflammatory bowel disease, receiving control, monotherapy, or combination therapy. Over 12 weeks, combination therapy demonstrated superior efficacy in enhancing gut microbial diversity. Improvements were achieved in alpha diversity, and a decrease in inflammatory indices and a shift in the immune phenotype were observed. Patients experienced significant improvements in symptom severity, pain, and general health. In addition, the general health of patients also improved. Importantly, the combination therapy group had better responses compared with the other groups. With respect to the identified factors, regression analysis revealed that microbial diversity, immune system regulation, and inflammation had positive effects on disease symptom alleviation. These findings therefore help support the perspective of combination therapy as a more comprehensive mode of approaching and treating gastroenteric diseases. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4290 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4290/2271