Expression of immune‐related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms

Abstract

Background Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune‐related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). Methods A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). Key Results A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3‐fold change), prostaglandin synthase PTGS2 (2.1‐fold change), and the G‐protein‐coupled receptor MRGPRX2 (10.7‐fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of “immuno‐active” IBS patients in the other patient cohort. Conclusion A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti‐inflammatory therapy remains to be investigated.

Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids

“…The vast majority of genes explored in our study, related to antibacterial response, inflammation and cell junctions, were more highly expressed by the colonoid monolayers stimulated with fecal supernatants from IBS patients compared to healthy subjects. The pro‐inflammatory cytokines IL‐1β 36 and TNF‐α, 37 the receptor TLR9 sensing unmethylated CpG dinucleotides of microbial DNA, 38 the antibacterial enzyme lysozyme 39 and transcription factors for type 1 interferons IRF5 and IRF7 38 reflect activation of the immune response and were all expressed to a higher degree in IBS patients. Interestingly, fecal supernatants from IBS patients also induced higher gene expression of CD1D, which encodes an MHC class I‐like molecule presenting bacterial lipid antigens to natural killer T cells (NKT cells).…”

Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

“…The relationships of mucosal inflammation or immune activation and symptoms or subgroups of IBS have been studied. Evidence of immune activation in the rectum and left colon was documented, though there was no relationship to symptoms or predominant bowel disturbance 40 41. In a study of colonic mucosal biopsies from patients with IBS (30 females with IBS-C, and 31 females and 13 males with IBS-D) there were differential expressions of 181 genes in ascending colon and 199 genes in rectosigmoid colon.…”

Immune Activation in Functional Dyspepsia: Bystander Becoming the Suspect

“…Moreover, atopy was 4-times more prevalent in responders compared to controls and immediate immune activation was evident from increased eosinophil degranulation and luminally released ECP ( Fritscher-Ravens et al, 2019 ). Also, in an “immuno-active” group of IBS patients, genes coding for the pro-inflammatory cytokine IL-1β and mast cell G-protein coupled receptor MRGPRX2, as well as the cyclooxygenase gene PTGS2 were significantly upregulated in the colon compared to healthy controls ( Aguilera-Lizarraga et al, 2019 ). All of these have been implicated in mast cell activation ( Aguilera-Lizarraga et al, 2019 ), with MRGPRX2 in specific mediating IgE-independent mast cell activation in response to various ligands including eosinophil cationic proteins ( Ali, 2016 ; Kumar et al, 2021 ).…”