On the Prevalence of M. avium Subspecies paratuberculosis DNA in the Blood of Healthy Individuals and Patients with Inflammatory Bowel Disease

Abstract

BackgroundMycobacteria, such as M. leprae and M. tuberculosis infect billions of humans. However, because of appropriate immune responses and antibiotic therapy, overt mycobacterial diseases occur far less frequently. M. avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants, an affliction evocative of inflammatory bowel disease (IBD). Several agents used to treat IBD (5-ASA, methotrexate, azathioprine and its metabolite 6-MP) have recently been shown to be antiMAP antibiotics. We herein evaluate the prevalence of MAP DNA in healthy individuals and compare them with IBD patients on antiMAP antibiotics.MethodsWe studied 100 healthy individuals (90 blood donors) and 246 patients with IBD. IS900 MAP DNA was identified using a nested primer PCR in the buffy coat of blood. Positive signal was confirmed as MAP by DNA sequence analysis. PCR positive results frequencies were compared according to medications used. Significance was accepted at p<0.05.Results47% (47/100) healthy controls and 16% (40/246) IBD patients were IS900 positive (p<0.0001). MAP DNA was identified in 17% of 143 patients receiving mesalamine and 6% of 16 receiving sulfasalazine. None of the IBD patients receiving methotrexate (n = 9), 6-MP (n = 3), ciprofloxacin (n = 5) or Tacrolimus® (n = 3) had MAP DNA detectable in their blood.DiscussionWe found a disquietingly large percentage of healthy individuals have MAP DNA in their blood, the significance of which remains to be determined. Counter-intuitively, the incidence of MAP DNA was significantly lower in patients with IBD. Agents with the most potent in vitro antiMAP activity were associated with clearance of blood MAP DNA. We posit that the use antiMAP antibiotics was responsible for the decreased prevalence of MAP DNA in patients with IBD.

In Vitro and In Vivo Properties of Dihydrophthalazine Antifolates, a Novel Family of Antibacterial Drugs

“…MICs of the dihydrophthalazines for pneumococci, group A streptococci, and M. catarrhalis were far lower than those of Tmp and comparable to those of Lvx. The dihydrophthalazines also showed very interesting activities against M. avium, an established pulmonary pathogen (30,38) which has been implicated in inflammatory bowel diseases (22,29) and which is the subject of considerable effort vis-à-vis antifolate therapy (1,21). However, BAL0030543, BAL0030544, and BAL0030545 showed relatively poor in vitro activities toward H. influenzae.…”

Pathogenesis of Crohn’s disease: Bug or no bug

“…Elguezabal et al [46] found a prevalence of 45.2% MAP DNA in the blood of healthy controls, compared to 21.38% and 19.04% in CD and UC patients respectively. The authors attributed the difference to therapy, as did Juste et al [48] , who found an even bigger difference between healthy controls (47% MAP DNA in blood) and IBD (16%). Juste et al [48] found that 17% of the patients receiving mesalamine, 6% of those taking sulfasalazine, and none of the ones taking methotrexate, mercaptopurine, ciprofloxacin or tacrolimus had MAP DNA detectable in blood; no difference was observed with azathioprine or steroids.…”

“…Humans worldwide are highly exposed to MAP. MAP has been cultured from pasteurized milk, chlorinated potable water, meat products, breast milk from mothers with CD, and from the blood of IBD patients [46,48] and controls.…”

Manipulation of Microbiome, a Promising Therapy for Inflammatory Bowel Diseases

“…Furthermore, the positive incidence is significantly higher in biopsies of terminal ileum and colon in CD patients than in those from healthy controls [67]. However, counteracting studies disproved such association [68][69][70][71]. Anti-MAP treatment with antibiotics does show short-term benefits in enhancing corticoid-induced remission, but hardly sustains the improvement over a longer course (156 weeks) [72].…”