Bacteroides fragilis Protects Against Antibiotic-Associated Diarrhea in Rats by Modulating Intestinal Defenses

Wendi Zhang, Bo Zhu, Jiahui Xu, Yangyang Liu, Enqi Qiu, Zhijun Li, Zhengchao Li, Yan He, Hongwei Zhou, Yang Bai, Fachao Zhi

Antibiotic-associated diarrhea (AAD) is iatrogenic diarrhea characterized by disruption of the gut microbiota. Probiotics are routinely used to treat AAD in clinical practice; however, the effectiveness and mechanisms by which probiotics alleviate symptoms remain poorly understood. We previously isolated a non-toxic Bacteroides fragilis strain ZY-312, which has been verified to be beneficial in certain infection disorders. However, the precise role of this commensal bacterium in AAD is unknown. In this study, we successfully established an AAD rat model by exposing rats to appropriate antibiotics. These rats developed diarrhea symptoms and showed alterations in their intestinal microbiota, including overgrowth of some pathogenic bacteria. In addition, gastrointestinal barrier defects, indicated by compromised aquaporin expression, aberrant tight junction proteins, and decreased abundance of mucus-filled goblet cells, were also detected in ADD rats compared with control animals. Of note, oral treatment with B. fragilis strain ZY-312 ameliorated AAD-related diarrhea symptoms by increasing the abundance of specific commensal microbiota. Interestingly, we demonstrated that these changes were coincident with the restoration of intestinal barrier function and enterocyte regeneration in AAD rats. In summary, we identified a potential probiotic therapeutic strategy for AAD and identified the vital roles of B. fragilis strain ZY-312 in modulating the colonic bacterial community and participating in microbiota-mediated epithelial cell proliferation and differentiation.