Sub clinical intestinal mucosal inflammation in diarrhea predominant Irritable Bowel Syndrome (IBS) in a tropical setting

Abstract

BACKGROUND: There is evidence for potential roles for gut flora and the host immune response in the pathophysiology of IBS, and especially, for low grade colonic mucosal inflammation in the pathophysiology of post-infectious IBS. AIM: To investigate for evidence of sub-clinical intestinal mucosal inflammation in diarrhea- predominant IBS (IBS-D) in a tropical setting. METHODS: In a prospective study over one year, we investigated 49 patients with IBS-D [median age 34 years (range 18-59; M:F 36:13], based on Rome III criteria. None had alarm symptoms: unintentional significant loss of weight, bleeding per rectum or malaena. None were on NSAIDS or proton pump inhibitors. All patients had normal ESR, CRP, TSH and stools reports. 14 individuals with a family history of colon cancer [median age 46.5 years (range 23-56); median 46.5, M:F 6:8] were selected as controls. Stools of patients and controls were tested for calprotectin. During colonoscopy, serial biopsies were obtained from the ileum, caecum, ascending, transverse and descending colon, and rectum. In addition to histology, tissue expression of IL-8 and IL-10 were assessed in biopsy specimens using semi-quantitative RT-PCR. RESULTS: Colono-ileoscopy was macroscopically normal and faecal calprotectin was undetectable in cases and controls. Microscopic colitis not otherwise specified(MNOS) was seen in 10/49 cases and 1/14 controls (p=0.43, Fisher's Exact test). Histology was normal in others. A history suggestive of an episode of infectious diarrhea (ID) was seen in 16/49 cases and 0/14 controls (p=0.013). There was no significant association between ID and the presence of MNOS. Tissue expression of IL-8 was significantly higher and IL-10 significantly lower in cases compared to controls (target/standard cDNA ratio, median (range) IL-8: 1.25 (0.75-2) Vs 0.85 (0.63-1.3), p<0.0001, Mann-Whitney U test; IL-10: 0.33 (0-0.63) Vs 0.55 (0.5-0.7), p<0.0001). There was a significant inverse correlation between IL-8 and IL-10 expression (Pearson Correlation, (-) 0.509; p<0.01). In patients with IBS-D, cytokine abnormalities were not significantly different in those with or without a history of ID or the presence or absence of MNOS. CONCLUSION: There is evidence for subclinical intestinal mucosal inflammation in patients with IBS-D in a tropical setting, whether or not a history of ID or MNOS was present or absent.