An Antibiotic-Treated Mouse Model Reveals the Progression of Intestinal Botulism

Intestinal botulism, including infant botulism and adult intestinal toxemia botulism, is a life-threatening disease caused by intestinal infection with Clostridium botulinum (Cb) spores. Infants are particularly susceptible to Cb infection because of their immature gut microbiota, whereas healthy adults are generally protected by gut microbiota-mediated colonization resistance. Thus, immature gut microbiota or gut dysbiosis is thought to permit Cb colonization. However, the mechanisms underlying colonization resistance and disease progression remain poorly characterized. Here, using adult mice with antibiotic-induced dysbiosis, we established a model for studying Cb infection and characterized intestinal colonization, bacterial expansion, BoNT accumulation, and disease progression during intestinal botulism. Intestinal botulism developed in antibiotic-treated mice after intragastric administration of strain 62A spores, whereas untreated adult mice showed no symptoms. In antibiotic-treated mice, Cb expanded over time in fecal samples, followed by accumulation of BoNT/A, which correlated with the progression of botulism symptoms. Cb growth and BoNT/A accumulation occurred mainly in the cecum and colon, but not in the small intestine. Furthermore, this mouse model was applicable to the analysis of intestinal botulism caused by other Cb strains, including 7I03-H, Okra, and Osaka05. Taken together, this mouse model provides a useful platform for elucidating the pathogenesis of intestinal botulism and developing novel therapeutic strategies.