Molecular evidence for Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease correlates with enhanced TNF-α secretion

BackgroundSupport for a role of Mycobacterium avium subspecies paratuberculosis in Crohn's disease is largely based on epidemiological evidence, as no data on mechanisms linking the presence of M. avium subspecies paratuberculosis with gut damage is available.AimsTo determine whether the presence of M. avium subspecies paratuberculosis contributes to the pathogenesis of Crohn's disease by promoting cytokine secretion within gut mucosa.Patients and methodsA total of 235 subjects were recruited: 63 with Crohn's disease, 53 with ulcerative colitis, 45 with irritable bowel syndrome and 74 normal controls. M. avium subspecies paratuberculosis status was defined by nested PCR using IS900 sequence. Gut mucosal organ cultures were established to detect cytokine secretion patterns.ResultsSignificantly higher tumour necrosis factor-α concentrations were found in culture supernatants for Crohn's disease compared to ulcerative colitis (p < 0.05), irritable bowel syndrome (p < 0.01) and controls (p < 0.0001). When tumour necrosis factor-α levels were correlated with the presence of M. avium subspecies paratuberculosis, significantly greater concentrations were only found in M. avium subspecies paratuberculosis-positive Crohn's disease patients (p < 0.05). Tumour necrosis factor-α levels in M. avium subspecies paratuberculosis-positive Crohn's disease were significantly higher than in M. avium subspecies paratuberculosis-positive ulcerative colitis (p < 0.01), M. avium subspecies paratuberculosis-positive irritable bowel syndrome (p < 0.05) and M. avium subspecies paratuberculosis-positive controls (p < 0.01) and all M. avium subspecies paratuberculosis-negative specimens.ConclusionsThe data link M. avium subspecies paratuberculosis with a pathogenic mechanism in Crohn's disease and is consistent with abnormal macrophage handling of M. avium subspecies paratuberculosis.