Association of Mycobacterium Avium paratuberculosis with Crohn's Disease: A large multicentre study from TB endemic region.

Abstract

The causal relationship between Crohn's disease (CD) and Mycobacterium avium subspecies paratuberculosis (MAP) remains controversial. This multicenter observational study was conducted across seven tertiary care centers in India enrolled newly diagnosed, treatment-naïve Crohn's disease (CD) patients as cases, and treatment-naïve intestinal tuberculosis (ITB), ulcerative colitis (UC), and healthy individuals undergoing sigmoidoscopy for hemorrhoids as controls. Mycobacterium avium subspecies paratuberculosis (MAP) detection was performed using serology for MAP antibodies, PCR, RT-qPCR, and solid/liquid cultures on blood and colonic biopsies. In situ PCR and immunohistochemistry (IHC) were additionally applied to paraffin-embedded tissue sections to evaluate MAP presence across groups. A total of 889 participants were recruited (CD=148, ITB=288, UC=251 and non-IBD controls=202) were included. The seropositivity of MAP was significantly higher in patients with CD compared to controls (20.6% [13/63] vs healthy controls: 16.2% [12/74]; ITB: 7.8% [9/116]; UC: 4.8% [4/84]; p<0.01). On tissue PCR analysis using IS900-specific sequence in colonic biopsies, statistically higher number of patients with CD were positive for MAP compared to controls (11% [9/82] vs 7.1% [5/70]; UC: 1% [2/188]; ITB: 0.5% [1/198]; p<0.01). On solid culture of biopsy samples, MAP was detected in 10% (5/50) of patients with CD compared to 4.1% (4/97) in ITB and 0% (0/78) in UC (p=0.02). However, this difference was not observed when analysed using liquid culture, IHC, in situ PCR, and PCR of blood samples. Findings of our study suggest an increased association of MAP and CD. Future studies should explore possible causal role of MAP in CD and potential therapeutic options to target MAP.