Reuterin alleviates Enterohemorrhagic Escherichia coli O157:H7-induced infectious diarrhea in mice through modulation of the gut microbiota.

Enterohemorrhagic Escherichia coli O157:H7 (EHEC O157:H7) is a globally significant foodborne pathogen. Infection disrupts the gut microbiota and exacerbates host immune dysfunction. Reuterin, a broad-spectrum antimicrobial metabolite produced by Limosilactobacillus reuteri during glycerol fermentation, exhibits potent antibacterial activity in vitro; however, its in vivo preventive efficacy and underlying mechanisms remain incompletely understood. This study aimed to comprehensively evaluate the protective effects of reuterin prophylaxis and to investigate its potential mechanisms in mitigating EHEC O157:H7 infection through gut microbiota modulation. In a murine infection model, prophylactic administration of reuterin (60 mM) conferred pronounced protection, as evidenced by alleviation of colonic pathology, oxidative stress, and systemic inflammation, together with restoration of intestinal barrier integrity. 16S rRNA sequencing and fecal microbiota transplantation (FMT) demonstrated that reuterin alleviated EHEC O157:H7 infection through gut microbiota remodeling, which was associated with elevated abundances of Ligilactobacillus and Alloprevotella and increased short-chain fatty acids (SCFAs) production. Exogenous SCFAs supplementation was associated with attenuated colonic damage and inflammation, consistent with a potential contribution of these metabolites to the observed protection. Furthermore, our data are compatible with a model wherein SCFAs-mediated activation of the intestinal receptor GPR43 may suppress NF-κB signaling. Collectively, this study provides a foundation for the further development of reuterin as a prophylactic agent against EHEC O157:H7 infection.