The Association of Mycobacterium avium subsp. paratuberculosis with Inflammatory Bowel Disease

Abstract

The association of Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) with Crohn’s disease is a controversial issue. M. paratuberculosis is detected by amplifying the IS900 gene, as microbial culture is unreliable from humans. We determined the presence of M. paratuberculosis in patients with Crohn’s disease (CD) (n = 22), ulcerative colitis (UC) (n = 20), aphthous ulcers (n = 21) and controls (n = 42) using PCR assays validated on bovine tissue. Culture from human tissue was also performed. M. paratuberculosis prevalence in the CD and UC groups was compared to the prevalence in age and sex matched non-inflammatory bowel disease controls. Patients and controls were determined to be M. paratuberculosis positive if all three PCR assays were positive. A significant association was found between M. paratuberculosis and Crohn’s disease (p = 0.02) that was not related to age, gender, place of birth, smoking or alcohol intake. No significant association was detected between M. paratuberculosis and UC or aphthous ulcers; however, one M. paratuberculosis isolate was successfully cultured from a patient with UC. We report the resistance of this isolate to ethambutol, rifampin, clofazamine and streptomycin. Interestingly this isolate could not only survive but could grow slowly at 5°C. We demonstrate a significant association between M. paratuberculosis and CD using multiple pre-validated PCR assays and that M. paratuberculosis can be isolated from patients with UC.

Risk Factors for the Presence of Mycobacterium avium spp. paratuberculosis in Human Intestinal Biopsies in Brazil

“…This was expected, given the frequent isolation of the agent in patients with CD, as previously discussed. Comparable results were found by Timms, et al (2016) that published a study reporting a significant association between MAP and CD that was not related to age, gender, and place of birth [22] Comparing cases and controls, we found that clinical treatment was received by 87.5% of cases and 68.3% of controls. In relation to surgical treatment, only 12.5% of the cases did not need a surgical procedure, while 67.6% of controls did undergo surgery.…”

Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals

“…The ability of MAP to exist in a variety of phenotypes, some with a high resistance to killing (Grant and Rowe, 2004), has increased the importance of providing accurate quantitative estimates of viable counts when testing for the presence of this pathogen in food (Botsaris et al, 2016; Galiero et al, 2016; Ricchi et al, 2016), animal and human samples (Timms et al, 2016). MAP is widely accepted as a difficult organism to culture reproducibly and accurately, particularly at low loads (Hines et al, 2007).…”

Altered pattern of tumor necrosis factor-alpha production in peripheral blood monocytes from Crohn's disease

“…A possible explanation is that peripheral monocytes from patients with CD are primed by mycobacterial components released in the intestinal mucosa, maybe as a result of colonization with bacteria such as mycobacterium avium paratuberculosis (MAP). The presence of MAP in CD intestinal mucosa and bloodstream has been proved by several works and accomplished by different techniques; it has been repetitively associated with the pathogenesis of CD but its role in the etiology remains to be defined[40]. Our results should prompt further investigation on the immune response to MAP in healthy population and in CD.…”