Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach

Abstract

Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. Methods Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein–protein interaction network was constructed and visualized using STRING database and Cytoscape. Results The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. Conclusions Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.

Antihyperalgesic properties of gut microbiota: Parabacteroides distasonis as a new probiotic strategy to alleviate chronic abdominal pain

“…Its contribution to visceral pain has been reported both in rodents 3,56,61 and humans. 29,36,55 Of interest, a cross talk between bradykinin receptors and TRPV1 channels has been documented in previous studies demonstrating a sensitization of the channel after activation of bradykinin receptors. 42 Conversely, blocking B2 through a receptor antagonist can abolish C-fiber responses, whereas blocking B1 has no effect.…”

“…present in the gut. 49,66 Because of its lowered abundance in diverse pathological contexts, and more particularly in IBD, 34,36 this strain was believed to provide beneficial effects to the host 59 through probiotic properties that depend on the bacterial strain. 8,20 However, deleterious effects have also been associated with end product fermentation of P distasonis such as succinic acid, which acts as a proinflammatory signaling molecule in immune cells.…”

Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead

“…Preclinical and clinical studies investigating genetic determinants of pain and visceral sensation have focused largely on identifying genetic variations associated with immune dysregulation, barrier function, neurotransmitter biosynthesis and metabolism, cannabinoid receptors, ion channel dysfunction, and G-protein coupled receptor expression alongside other mechanisms. 27 , 149 The increasing availability of large-scale population-based biobanks have facilitated advancements in genomic research in IBS 150 that may accelerate our understanding of genetic risk determinants in IBS. In one genome-wide association study of 53,400 people with IBS, six genes ( NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6 ) were found to be associated with IBS susceptibility including four genes linked to mood, anxiety, or expressed in the nervous system.…”

“…In a pilot cohort of 9 patients with IBS-D and 9 controls, RNA-seq of rectosigmoid biopsy specimens demonstrated transcriptome changes involving neurotransmitters, ion channels, immune function and cytokines, barrier function, as well as cell adhesion in patients with IBS. 156 Microarray analysis of rectal mucosal specimens and bioinformatics approaches have recently implicated genes including GRPR , neuropeptide FF ( NPFF ), and TRPA1 to be associated with abdominal pain in IBS-D. 149 Gene expression profiling of colonic biopsy specimens with microarray analysis has also demonstrated pathways involved in 5-HT metabolism to be differentially expressed between IBS and controls, suggesting transcriptional patterns of serotonergic gene expression including TPH1 as potential biomarkers for IBS. 157 …”

The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management

“…Despite gaps in our understanding of the role of CCK2R in pain modulation, an increasing number of transcriptomic analyses underway in pain models, are highlighting the upregulation of CCK2R in several models including abdominal pain in patients with irritable bowel syndrome [76], a model of lipopolysaccharide-induced lung inflammation [77] and a model of deletion of the NMDA receptor inducing hypersensitivity [78]. This upregulation demonstrated a central role of CCK2R in pain development.…”