The role of gastrointestinal PCR in inflammatory bowel disease flares: A double-edged sword or a diagnostic breakthrough?

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic gastrointestinal inflammation, leading to unpredictable flares and substantial morbidity. Gastrointestinal polymerase chain reaction (GI-PCR) testing has emerged as a widely used diagnostic tool to identify enteric pathogens during IBD exacerbations. It is a novel, quick and sensitive diagnostic test to detect Clostridioides difficile infection (CDI), as well as other enteric pathogens. However, the clinical significance of non-C. difficile pathogens detected by GI-PCR remains uncertain, raising concerns about the over-interpretation of positive results and the potential for unnecessary antimicrobial therapy. While traditional stool culture and microscopy offered limited sensitivity, GI-PCR has dramatically improved pathogen detection rates, identifying infections in up to 26% of IBD patients compared to 5% with conventional methods. Beyond C. difficile, pathogens such as Escherichia coli (especially adherent-invasive strains), Campylobacter, Salmonella, Norovirus and Yersinia enterocolitica are frequently detected in IBD flares. However, whether these microbes actively drive disease exacerbations or merely reflect inflammation-associated dysbiosis remains unclear. Enterobacteriaceae, in particular, bloom in inflamed intestines, raising critical questions regarding their pathogenic role vs. colonization. The high sensitivity of GI-PCR further complicates clinical decision-making, as distinguishing active infection from harmless microbial presence is challenging. This review explores the current literature on GI-PCR in IBD, emphasizing its benefits and limitations. While GI-PCR provides rapid, comprehensive pathogen detection, its indiscriminate application may lead to unnecessary antibiotic use and therapeutic missteps. Understanding the ecological shifts in IBD-associated dysbiosis and refining clinical interpretation of GI-PCR results are essential to optimizing patient management. Future research should aim to delineate the pathogenic significance of non-C. difficile microbes and establish evidence-based protocols for the appropriate use of GI-PCR in IBD care.