Abstract
Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder, worldwide, with a high prevalence among Mestizo Latin Americans. Because several inflammatory disorders appear to affect this population, a further understanding of host genomic background variants, in conjunction with colonic mucosa dysbiosis, is necessary to determine IBS physiopathology and the effects of environmental pressures. Using a simple polygenic model, host single nucleotide polymorphisms (SNPs) and the taxonomic compositions of microbiota were compared between IBS patients and healthy subjects. As proof of concept, five IBS-Rome III patients and five healthy controls (HCs) were systematically studied. The human and bacterial intestinal metagenome of each subject was taxonomically annotated and screened for previously annotated IBS, ulcerative colitis, and Crohn's disease-associated SNPs or taxon abundance. Dietary data and fecal markers were collected and associated with the intestinal microbiome. However, more than 1,000 variants were found, and at least 76 SNPs differentiated IBS patients from HCs, as did associations with 4 phyla and 10 bacterial genera. In this study, we found elements supporting a polygenic background, with frequent variants, among the Mestizo population, and the colonic mucosal enrichment of Bacteroides, Alteromonas, Neisseria, Streptococcus, and Microbacterium, may serve as a hallmark for IBS.
Highlights
Irritable bowel syndrome (IBS) is a multifactorial disorder, caused by abnormalities within the gut-brain axis and resulting in autonomic hypersensitivity and gastrointestinal motility dysfunction (Distrutti et al, 2016)
The most representative phyla were Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, and Verrucomicrobia, which were present in all metagenomes, with the exception of Fusobacteria, which was absent in one IBS patient (Table 2)
In our IBS group, we identified the following single nucleotide polymorphisms (SNPs): rs6495121, which is found in the aryl hydrocarbon receptor (AHR), which regulates toxicity via cytochrome P450 1A1 (CYP1A1) and G-proteincoupled receptor 35 (GPR35); rs2228099, a candidate for type II diabetes and prediabetes intermediate traits (Figure 1C and Table S1)
Summary
Irritable bowel syndrome (IBS) is a multifactorial disorder, caused by abnormalities within the gut-brain axis and resulting in autonomic hypersensitivity and gastrointestinal motility dysfunction (Distrutti et al, 2016). Corticotropin-releasing factor (CRF), NOD-like receptor family pyrin domain containing 6 (NLRP6 or IDO1), nucleotidebinding oligomerization domain-containing protein 2 (NOD2), Toll-like receptor 4 (TLR4), and cytochrome P450 1A (CYP1a) have been associated with low butyrate levels and colonic mucosal inflammation in humans and animal model of IBS, demonstrating the effects of genomic background on crosssignaling (Vujkovic-Cvijin et al, 2015; Wang et al, 2016; Layunta et al, 2018; Manzella et al, 2018; Martin-Gallausiaux et al, 2018; Zhao et al, 2018; Yu et al, 2019) Hypothesisfree analyses, such as genome-wide association studies (GWAS) may be able to disentangle all possible interactions, a major drawback of IBS standardized trials is that most have been lowpowered and primarily focused on participants with Caucasian ancestry (Gazouli et al, 2016). Shotgun metagenome sequencing and analysis remains a fast and sensitive alternative for the exploration of gene network variants and microbiota phylogeny among a standardized cohort, providing the opportunity to explore both the microbial community and host interactions in IBS patients with particular genetic backgrounds (Sharpton, 2014)
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