Study of animal-borne infections in the mucosas of patients with inflammatory bowel disease and population-based controls

Abstract

Crohn's disease may be triggered by an infection, and it is plausible to consider that such an infection may be animal borne and ingested with our food. There has been considerable interest in the past in determining whether Mycobacterium avium subsp. paratuberculosis (M. avium) might be the etiologic agent in Crohn's disease since it causes a disease in cattle that is similar to Crohn's disease in humans. We aimed to determine if there was an association between Crohn's disease and infection with M. avium or other zoonotic agents and compared the findings with those for patients with ulcerative colitis, unaffected siblings of Crohn's disease patients, or population-based controls without inflammatory bowel disease. Patients under age 50 years with Crohn's disease or ulcerative colitis, unaffected siblings of patients, or healthy controls drawn from a population-based age- and gender-matched registry were enrolled in a study in which subjects submitted to a questionnaire survey and venipuncture. A nested cohort underwent colonoscopy plus biopsy. Samples were batched and submitted to PCR for the detection of M. avium and other zoonotic agents known to cause predominately intestinal disease in cattle, sheep, or swine. Only one patient with ulcerative colitis, no patients with Crohn's disease, and none of the sibling controls were positive for M. avium, whereas 6 of 19 healthy controls were positive for M. avium. Since the control subjects were significantly older than the case patients, we studied another 11 patients with inflammatory bowel disease who were older than age 50 years, and another single subject with ulcerative colitis was positive for M. avium. One other subject older than age 50 years with ulcerative colitis was positive for circovirus, a swine-borne agent of infection. In conclusion, by performing PCR with mucosal samples from patients with Crohn's disease and controls, no association between Crohn's disease and infection with M. avium or any of the other six zoonotic agents studied could be found.

FIG. 1.

Samples C2 and C11 retested positive two more times by nested PCR, and all other samples, including sample C8, retested negative two more times by nested PCR for M. avium. The band for sample C8 might have been weakly positive because the amount of the organism present was just barely at the lower detection limit of our nested PCR or the test might have had a false-positive result. In such situations, we reported sample C8 as being negative. All other samples that were processed on the same day before and after samples C2 and C11 were tested consistently retested negative. Several negative samples were randomly chosen and retested negative for M. avium by nested PCR. POS, positive control; neg, negative control. The numbers on the right are in base pairs.