Unraveling the Pathogenetic Potential and Immune Crosstalk of Yersinia spp. in Inflammatory Bowel Disease

Yersinia enterocolitica and Yersinia pseudotuberculosis have been identified as microbiological factors in the multifactorial pathophysiology of inflammatory bowel disease (IBD). Although conventionally associated with self-limiting gastroenteritis, Yersinia has been increasingly investigated for its potential role in IBD, particularly in genetically predisposed individuals. Whether this reflects causality, opportunistic colonization, or secondary enrichment within inflamed tissue, however, remains unresolved. Polymerase chain reaction (PCR)-based studies have detected Yersinia DNA in the intestinal tissues of patients with IBD, and epidemiological studies have suggested an association between prior Yersinia infection and an increased long-term risk of disease. However, because most evidence is based on PCR detection, with limited culture-based confirmation of viable organisms and infrequent sequencing of PCR amplicons, these findings do not establish active infection or a causal relationship. These pathogens exploit abnormalities in the epithelial barrier and compromised mucosal immunity through type III/VI secretion systems to disrupt host responses, activate inflammasomes, and induce pyroptosis. Polymorphisms in autophagy-related genes, such as NOD2 and ATG16L1, impair pathogen clearance and increase susceptibility. While antibiotics continue to be effective against invasive diseases, the rise of resistance highlights the necessity for alternatives. Probiotic-based strategies have demonstrated immunomodulatory, antimicrobial, and barrier-protective effects in preclinical models, although their therapeutic efficacy in IBD requires further clinical validation. Comprehending Yersinia-host genetic interactions could facilitate precision diagnostics and microbiota-targeted treatments in IBD.