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

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-1α and β 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 age- and gender-matched HS were included. Exactly 209 of 221 patients (Rome III) and 273 HS were genotyped (PCR) for IL-1RA polymorphism. Mucosal IL-1α and β 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-1α and β were higher among patients with SIBO than without (IL-1α: 35.4 [20.1-66.8] vs 25.5 [4.2-65.3], p < 0.001; IL-1β: 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-1β 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 (under-producers) frequent among IBS. Increased IL-1α and β levels were associated with SIBO. Increased IL-1β level was predominantly associated with bloating and loose stools (Bristol type 6).