A naturally isolated symbiotic Lactobacillus murinus suppresses multidrug-resistant Campylobacter jejuni via microbial metabolites

Multidrug-resistant Campylobacter jejuni (MDR C. jejuni ), the leading cause of food-borne gastroenteritis worldwide, poses a significant threat to public health and food safety. The intestinal microbiota prevents MDR C. jejuni colonization, but the specific mechanisms remain poorly understood. In this study, we performed a multi-omics analysis of the gut microbiota in C57BL/6 mice, combined with in vitro experiments, to investigate the role of gut microbiota in C. jejuni colonization. Treatment with tylvalosin, a new macrolide, altered the gut microbiota composition, reducing Bifidobacterium longum communities and decreasing levels of short-chain fatty acids (acetic acid, propionic acid, n -butyric acid, i -butyric acid, and i -valeric acid). This disruption of intestinal homeostasis facilitated C. jejuni colonization. Through metagenomic sequencing, we identified and isolated Lactobacillus murinus ( L. murinus ) from the mice’s intestinal flora, which exhibited inhibitory activity against C. jejuni in vitro . Metabolomic analysis and in vitro validation further revealed the significance of L. murinus -derived metabolites. Our results indicate that L. murinus inhibits and kills C. jejuni in a co-culture system by secreting acids that synergistically induce apoptosis, leading to cell membrane disruption and the release of cellular contents.