Associations between IL-1RA polymorphisms and small intestinal bacterial overgrowth among patients with irritable bowel syndrome from India

摘要

Background Low-grade inflammation (controlled by pro and anti-inflammatory molecules), induced by gut microbes in patients with small intestinal bacterial overgrowth (SIBO), may be associated with irritable bowel syndrome (IBS). Polymorphisms of IL-RA gene (anti-inflammatory) was evaluated in IBS and healthy subjects (HS); small intestinal mucosal IL-1 alpha and beta levels (pro-inflammatory) in relation to the presence of SIBO were evaluated in a subset of patients. Methods Two hundred and twenty-one IBS patients and 273 ageand gender-matched HS were included. Exactly 209 of 221 patients (Rome III) and 273 HS were genotyped (PCR) for IL-1RA polymorphism. Mucosal IL-1 alpha and beta levels (pg/mg of biopsy) were estimated (ELISA) in 82/221 patients with and without SIBO (>= 10(5) CFU/mL upper gut aspirate bacteria). Key Results Genotype 1/1 (IL-1RA over-producer) was less frequent among patients than controls (p = 0.007); genotypes 1/3 (p = 0.012, OR = 3.301, 95% CI = 1.31-8.35) and 2/3 (both under-producers; p = 0.009, OR = 7.703, 95% CI = 1.66-35.82) were commoner among IBS. Fifteen of 82 (18.3%) patients had SIBO. Levels of IL-1 alpha and b were higher among patients with SIBO than without (IL-1 alpha: 35.4 [20.16-6.8] vs 25.5 [4.2-65.3], p < 0.001; IL-1 beta: 206.8 [133.5-365.9] vs 93.1 [25.5-197.7], p < 0.001) and those with bloating than without (p = 0.012; p = 0.015). IL-1b was higher among patients with Bristol stool type 6 than those with type 1-2 (p = 0.002) and type 3-5 (p = 0.007). Conclusions & Inferences Polymorphisms 1/1 (IL-1RA over-producer) was infrequent and 1/3 and 2/3 (underproducers) frequent among IBS. Increased IL-1 alpha and beta level was predominantly associated with bloating and loose stools ( Bristol type 6).