Gene Expression Profiling and Assessment of Vitamin D and Serotonin Pathway Variations in Patients With Irritable Bowel Syndrome

Abstract

Background/AimsIrritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS. MethodsGene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay. ResultsA total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls. Conclusions IntroductionIrritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders afflicting between 10-15% of the global population.1 Primary symptoms associated with IBS include abdominal pain and irregular bowel movements that, based upon the predominant symptom pattern, may be utilized to subdivide the syndrome into 3 classifications: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C), and mixed IBS (IBS-M).2 However, the subtype of IBS that an individual is classified does not necessarily remain static; patients can evolve over time from diarrheic or mixed type to constipative. The chronic and erratic nature of IBS can lead to a multitude of secondary effects, such as depression, anxiety, poor quality of life, insomnia, and sexual dysfunction. 3Using the current diagnostic model for IBS, the Rome IV criteria, symptoms must be present for 3 months or longer before diagnoses can be established. 4 Other disorders with IBS-like symptoms that should be excluded include celiac disease, inflammatory bowel disease (IBD), malabsorptive disorders, pelvic floor disorders, and colon cancer. Further, once diagnosed, treatment for IBS patients may be mostly palliative in nature with dietary changes...

Characteristics of fecal metabolic profiles in patients with irritable bowel syndrome with predominant diarrhea investigated using 1H‐NMR coupled with multivariate statistical analysis

“…Further studies are needed on the role of threonine in IBS‐D. Tryptophan, which is converted to serotonin, is known to be associated with IBS, as the increased serotonin levels lead to increased GI motility and visceral hypersensitivity . Previous studies have shown that patients with IBS‐D have comparatively higher levels of free serum tryptophan than those in HC .…”

Gut instincts: vitamin D/vitamin D receptor and microbiome in neurodevelopment disorders

“…TPH2 knockout mice show intestinal dysmotility. Serotonin dysregulation, secondary to vitamin D deficiency, has been linked to Inflammatory bowel syndrome [ 41 ] and inflammatory bowel disease [ 99 , 100 ]. It is possible that serotonin is the common mediator in the changes seen in each of these conditions.…”

Transcriptome and methylome profiling in a rat model of irritable bowel syndrome induced by stress

“…A previous small bowel mucosal gene expression study has reported that both transcriptome expression and immune-related mechanisms are altered in IBS-D patients ( 27 ). Another DNA microarray analysis has demonstrated that IBS is associated with abnormal serotonin metabolism and vitamin D deficiency ( 28 ). Currently, most omics studies only report the observational results of IBS-related differentially expressed genes (DEGs).…”