Modulation of Gut Microbiota and Immune Response by Soy Peptides Mitigates Irinotecan-Induced Intestinal Toxicity

Yongfa Jing^1*Dongli Yan²

• ¹Handan First Hospital, Handan, China
• ²Hebei Runkang Medical Technology Co., Ltd., Handan, China

Irinotecan (CPT-11), a widely used chemotherapy agent, is associated with significant gastrointestinal toxicities, such as diarrhea, which adversely impact patients' treatment tolerance and quality of life. This study investigates the protective effects of soy peptides (SPs) against irinotecan-induced diarrhea and intestinal damage, with a focus on gut microbiota modulation and related mechanisms. In a murine model, irinotecan treatment resulted in severe diarrhea, weight loss, and intestinal damage. Soy peptides intervention effectively alleviated these symptoms, restored intestinal barrier integrity, and reduced intestinal inflammation. Histological examination revealed that soy peptides restored intestinal architecture, reduced epithelial injury, and mitigated inflammatory cell infiltration.16S rRNA sequencing further demonstrated that irinotecan significantly altered the gut microbiota composition, decreasing the abundance of beneficial bacteria and promoting the growth of pathogenic microbes.Soy peptides restored microbiota diversity, notably increasing the abundance of beneficial bacteria, including Lactobacillus and Bifidobacterium.Immunohistochemistry and ELISA analyses showed that soy peptides suppressed the overexpression of inflammatory cytokines (e.g., TNF-α, IL-6), thereby promoting immune-mediated intestinal repair. These findings suggest that soy peptides protect against irinotecan-induced intestinal toxicity through multiple mechanisms, including microbiota regulation, immune modulation, and intestinal barrier restoration, highlighting their potential as a therapeutic candidate for chemotherapy-induced intestinal damage.