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

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