Background:Although Clostridium difficile may be associated with exacerbations in inflammatory bowel diseases (IBD), prospective studies identifying the role of C. difficile in disease activity are currently lacking. We examined the prevalence of C. difficile in feces of (1) symptomatic IBD patients retrospectively and (2) consecutive outpatients in relation to disease activity prospectively.Methods:From adult IBD patients with increase of symptoms, fecal samples collected between November 2010 and 2011 were tested for C. difficile, Salmonella, Shigella, Yersinia, and Campylobacter spp. Within a prospective IBD cohort, fecal samples, clinical data, and disease activity scores were collected every 3 months and during relapses. Baseline samples from all subjects (170 Crohn's disease, 116 ulcerative colitis) and additional samples from patients with changing disease activity during follow-up (57 Crohn's disease, 31 ulcerative colitis) were tested for C. difficile and when positive for toxin A and B genes by quantitative polymerase chain reaction.Results:From 104 symptomatic patients, 139 fecal samples were analyzed. Toxinogenic C. difficile and Campylobacter jejuni were detected in 3.6% and 1.8%. In the prospective cohort, C. difficile prevalence at baseline was significantly different neither between ulcerative colitis (3.4%) and Crohn's disease patients (5.9%) nor between active (8.2%) and quiescent (3.3%) disease. In multivariable analysis, C. difficile was not associated with disease activity, disease subtype, gender, antibiotic, and immunosuppressive therapy. Clostridium difficile was also not associated with disease activity within patients with changing disease activity over time (P = 0.45).Conclusions:We found a low prevalence of C. difficile, and our findings indicate that C. difficile is not a common trigger for exacerbations of IBD in clinical practice in the Netherlands.