Uridine mitigated Listeria monocytogenes infection in mice by improving gut microbiota and protecting the intestinal barrier

Abstract

Abstract This study investigated the protective effects of uridine against Listeria monocytogenes infection in mice and explored the underlying mechanisms. Uridine markedly suppressed pathogen loads in the liver and spleen, mitigating infection-induced pathological damage. In terms of systemic inflammation, uridine significantly reduced serum levels of IL-6, TNF-α and IL-1β. Moreover, uridine upregulated the mRNA and protein expression of tight junction proteins (ZO-1, Claudin-1, Occludin) and Mucin-2, while inhibiting activation of the myosin light chain kinase (MLCK)-MLC signaling pathway, thus preserving barrier integrity. In addition, uridine increased fecal levels of short-chain fatty acids (SCFAs), particularly propionate and valerate, and modulated gut microbiota composition. Collectively, these findings demonstrate that uridine protects against L. monocytogenes infection by suppressing inflammation, strengthening the intestinal barrier, promoting SCFA production, and modulating the gut microbiota. This work provides important theoretical and experimental evidence supporting the development of uridine-based agents for prevention or mitigation of listeriosis.