AUTHOR=Deng Huimin , Yang Siqi , Zhang Yucheng , Qian Kai , Zhang Zhaohui , Liu Yangyang , Wang Ye , Bai Yang , Fan Hongying , Zhao Xinmei , Zhi Fachao 

TITLE=Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02976

DOI=10.3389/fmicb.2018.02976

ISSN=1664-302X

ABSTRACT=<p><italic>Clostridium difficile</italic> is currently the leading cause of nosocomial infection. Antibiotics remain the first-line therapy for <italic>C. difficile</italic>-associated diseases (CDAD), despite the risks of resistance promotion and further gut microbiota perturbation. Notably, the abundance of <italic>Bacteroides fragilis</italic> was reported to be significantly decreased in CDAD patients. This study aimed to clarify the prophylactic effects of <italic>B. fragilis</italic> strain ZY-312 in a mouse model of <italic>C. difficile</italic> infection (CDI). The CDI mouse model was successfully created using <italic>C. difficile</italic> strain VPI 10463 spores, as confirmed by lethal diarrhea (12.5% survival rate), serious gut barrier disruption, and microbiota disruption. CDI model mice prophylactically treated with <italic>B. fragilis</italic> exhibited significantly higher survival rates (100% in low dosage group, 87.5% in high dosage group) and improved clinical manifestations. Histopathological analysis of colon and cecum tissue samples revealed an intact gut barrier with strong ZO-1 and Muc-2 expression. The bacterial diversity and relative abundance of gut microbiota were significantly improved. Interestingly, the relative abundance of <italic>Akkermansia muciniphila</italic> was positively correlated with <italic>B. fragilis</italic> treatment. <italic>In vitro</italic> experiments showed that <italic>B. fragilis</italic> inhibited <italic>C. difficile</italic> adherence, and attenuated the decrease in CDI-induced transepithelial electrical resistance, ZO-1 and MUC-2 loss, and apoptosis, suggesting that <italic>B. fragilis</italic> protected against CDI possibly by resisting pathogen colonization and improving gut barrier integrity and functions. In summary, <italic>B. fragilis</italic> exerted protective effects on a CDI mouse model by modulating gut microbiota and alleviating barrier destruction, thereby relieving epithelial stress and pathogenic colitis triggered by <italic>C. difficile</italic>. This study provides an alternative preventative measure for CDI and lays the foundations for further investigations of the relationships among opportunistic pathogens, commensal microbiota, and the gut barrier.</p>