Campylobacter jejuni infection impacts host-derived miRNAs targeting bacterial and host genes

The intestinal microbiota has been shown to influence host-derived microRNAs (miRNAs), small regulatory RNAs involved in host-pathogen interactions. However, the specific role of individual bacterial species in modulating host extracellular vesicles (EV)-derived miRNA profiles remains unclear. We compared stool miRNA profiles from three groups: (i) Germ-free (GF) mice, (ii) mice colonized with a consortium of 13 bacteria (C13), and (iii) mice colonized with C13 and Campylobacter jejuni 81-176 (C13 + C. jejuni). miRNA profiling revealed unique differential expression of 8 miRNAs in C13 vs GF, 38 in C13 + C. jejuni vs C13, and 159 in C13 + C. jejuni vs GF (P_adj < 0.05), indicating a substantial shift in host miRNA landscape following C. jejuni exposure. Notably, C13 + C. jejuni mice showed increased expression of miRNAs predicted to target bacterial virulence genes, suggesting a potential host response mechanism aimed at regulating microbial activity. Integration with spatial transcriptomics of the mouse colon revealed that specific EV-derived miRNAs, including mmu-miR-155-5p, mmu-miR-122-5p, mmu-miR-21a-5p, mmu-let-7i-5p, and mmu-miR-142a-3p target epithelial genes involved in immune regulation, inflammation, and barrier function. C. jejuni exposure selectively enriched these host miRNAs, suggesting a mechanism by which EVs modulate epithelial transcriptional responses and potentially influence microbial gene expression. In conclusion, C. jejuni infection modified host EV-derived miRNA expression profile that may have a potential to bind to the bacterial gene targets.

Host-derived microRNAs (miRNAs) are known to regulate bacterial gene expression and maintain gut homeostasis. However, how these miRNAs survive harsh gut conditions to remain functional is not fully understood. This study tested whether extracellular vesicles (EV) carry microRNAs in the gut and whether infection with the enteric pathogen Campylobacter jejuni alters the microRNA profile packaged in these vesicles. We utilized fecal samples from mice, either maintained germ-free (absence of microbiota) or, C13 (defined 13 bacterial consortium), and C13 + C. jejuni to analyze the EV-derived miRNA pattern across the groups. Our results revealed distinct sets of miRNAs in each group and suggested possible interactions between these miRNAs and gene transcripts from both the host and bacteria. These findings provide new insights into how C. jejuni infection may change communication between the host and its microbiome, potentially affecting gut health and disease.