Multifactor dimensionality reduction analysis revealed that there were no significant interactions of GNB3, IL-10, and TNF-alpha gene variants with susceptibility to IBS (P > 0.05).
An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.
When comparing IBS subtypes, TNFα and IL-17 were significantly (P<0.05) higher, and IL-10 was significantly (P<0.05) lower in diarrhea predominant IBS (IBS-D) compared to HCs, whereas the inflammatory cytokine profile of other subtypes more closely resembled that of HCs.
Two IL-10 single nucleotide polymorphisms (rs1800871 and rs1800896) were detected in 120 patients with IBS-D and 144 healthy controls (HC) using SNaPshot.
Possession of a high producer TNF-alpha and a low producer IL-10 genotype were significantly more prevalent in IBS (9%) versus controls (3%, p= 0.035; OR 3.11, 95% CI 1.03-9.36) and in diarrhea (20%) compared to other IBS subtypes (<4%, p= 0.026).
Patients with irritable bowel syndrome had significantly reduced frequencies of the high producer genotype for interleukin 10 than controls (21% v 32%; p=0.003).
Genetic association studies with IBS symptom phenotype have generally provided inconsistent results for many candidate genes investigated, such as SLC6A4, GNB3, and IL-10.
Stimulation with Eubacterium limosum resulted in a significantly decreased IL-10 release in HC compared to PI-IBS patients (p < 0.05) and a tendency to decreased IL-13 release in HC compared to PI-IBS patients (p = 0.07).
While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.
IBS-SSS was associated with high tumor necrosis factor and low IL-10 in the CSF; pc = 0.341 and <i>p</i> = 0.009 and pc = -0.299 and <i>p</i> = 0.023, respectively.
Our results suggest that some IL-8 and IL-10 SNPs could change individual susceptibility increasing the relative risk in the development of IBS in Blastocystis carriers.
These preclinical studies contrast with the limited clinical positive outcome of CRF-R1 antagonists to alleviate stress-sensitive functional bowel diseases such as irritable bowel syndrome.