Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease: common neural and immune pathogenicities

Abstract

Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacterium avium subsp. paratuberculosis infection and irritable bowel syndrome. Mucosal biopsy specimens from the ileum and the ascending and descending colon were obtained from patients with irritable bowel syndrome attending the University of Sassari, Sassari, Sardinia, Italy. Crohn's disease and healthy control groups were also included. Mycobacterium avium subsp. paratuberculosis was detected by IS900 PCR with amplicon sequencing. Data on the potential risk factors for human exposure to these pathogens and on isolates from Sardinian dairy sheep were also obtained. Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease (P = 0.0003 for irritable bowel syndrome patients versus healthy controls and P = 0.0000 for Crohn's disease patients versus healthy controls). One subject in each group had a conserved single-nucleotide polymorphism at position 247 of IS900 that was also found in isolates from seven of eight dairy sheep. There was a significant association (P = 0.0018) between Mycobacterium avium subsp. paratuberculosis infection and the consumption of hand-made cheese. Mycobacterium avium subsp. paratuberculosis is a candidate pathogen in the causation of a proportion of cases of irritable bowel syndrome as well as in Crohn's disease.

FIG. 1.

(Upper panel) The normal appearances at endoscopy of a female patient aged 47 years with constipation-predominant IBS in the IBS group. T, terminal ileum; A, ascending colon; D, descending colon. (Lower panel) Results of IS900 PCR testing for Mycobacterium avium subsp. paratuberculosis in the same patient at each of the three sites sampled. The results are consistent with an extensive Mycobacterium avium subsp. paratuberculosis infection in her gastrointestinal tract. Lanes: B, negative buffer control; M, negative process control; +, positive PCR control.

FIG. 2.

Sequence electropherogram spanning the previously undescribed C/T ambiguity (code Y) found in the AV1 and AV2 amplicons at position 247 of the IS900 element and identified in Mycobacterium avium subsp. paratuberculosis isolates from three humans and seven of eight Sardinian dairy sheep in the present study. It is consistent with a situation in which a proportion of the 14 to 18 copies of the IS900 elements in the affected Mycobacterium avium subsp. paratuberculosis isolates underwent a C-to-T transition from the characteristic bovine genotype at this locus.