Bifidobacteria and Clostridioides difficile infection: review of emerging therapeutic perspectives

Clostridioides difficile infection (CDI) remains a major cause of antibiotic-associated diarrhea and colitis, with a high rate of recurrence. Current CDI treatments rely largely on antibiotics that perpetuate dysbiosis or on microbiota-based interventions with limited accessibility, emphasizing the need to explore novel, targeted microbiota-derived therapies. Probiotics have emerged as a potential approach for the prevention and management of CDI, owing to their capacity to modulate the gut microbiota and host immune responses. Among them, bifidobacteria are prominent commensal anaerobes of the human gut with well-documented health-promoting properties. Although their role in CDI has been less extensively explored than that of other probiotic microorganisms, accumulating evidence suggests that bifidobacteria may exert both direct antagonistic effects against C. difficile and indirect benefits through the restoration of eubiosis and attenuation of inflammation. This review summarizes recent in vitro, in vivo, and clinical studies investigating the effects of bifidobacteria in the context of CDI. We discuss mechanisms including inhibition of C. difficile growth and toxin activity, modulation of host inflammatory responses, and interactions with the intestinal microbiota. Particular attention is given to studies published over the past decade. Overall, bifidobacteria emerge as promising candidates for future probiotic or microbiota-based interventions targeting CDI, although further well-designed clinical trials are needed to establish their efficacy and optimal modes of use.