Association of Mycobacterium avium paratuberculosis With Crohn's Disease: A Large Multicenter Study From a Tuberculosis-Endemic Region.

BACKGROUND

The causal relationship between Crohn's disease (CD) and Mycobacterium avium subspecies paratuberculosis (MAP) remains controversial.

METHODS

This multicenter observational study, conducted across 7 tertiary care centers in India, enrolled newly diagnosed, treatment-naive patients with CD as cases and treatment-naive patients with intestinal tuberculosis (ITB) or ulcerative colitis (UC) and healthy individuals undergoing sigmoidoscopy for hemorrhoids as controls. MAP detection was performed using serology for MAP antibodies, polymerase chain reaction (PCR), real-time quantitative PCR, and solid/liquid cultures of blood and colonic biopsy specimens. In situ PCR and immunohistochemistry were also applied to paraffin-embedded tissue sections to evaluate the presence of MAP across groups.

RESULTS

A total of 889 participants were recruited (148 with CD, 288 with ITB, 251 with UC, and 202 controls without inflammatory bowel disease) were included. The seropositivity of MAP was significantly higher in patients with CD than in controls (20.6% [13 of 63] vs 16.2% [12 of 74] for healthy controls, 7.8% [9 of 116] for patients with ITB, and 4.8% [4 of 84] for patients with UC; P < .01). With tissue PCR analysis using a IS900-specific sequence with colonic biopsy specimens, a significantly higher number of patients with CD were positive for MAP compared with controls (11% [9 of 82] vs 7.1% [5 of 70] for healthy controls, 1% [2 of 188] for patients with UC, and 0.5% [1 of 198] for patients with ITB; P < .01). On solid culture of biopsy samples, MAP was detected in 10% of patients with CD (5 of 50), compared with 4.1% (4 of 97) for ITB and 0% (0 of 78) for UC (P = .02). However, this difference was not observed with analysis using liquid culture, immunohistochemistry, in situ PCR, or PCR of blood samples.

CONCLUSIONS

Our study findings suggest an increased association between MAP and CD. Future studies should explore the possible causal role of MAP in CD and potential therapeutic options to target MAP.