Abstract
Irritable bowel syndrome (IBS) is a brain-gut axis disorder characterized by abdominal pain and altered bowel habits. IBS is a multifactorial, stress-sensitive disorder with evidence for familial clustering attributed to genetic or shared environmental factors. However, there are weak genetic associations reported with IBS and a lack of evidence to suggest that major genetic factor(s) contribute to IBS pathophysiology. Studies on animal models of stress, including early life stress, suggest a role for environmental factors, specifically, stress associated with dysregulation of corticotropin releasing factor and hypothalamus-pituitary-adrenal (HPA) axis pathways in the pathophysiology of IBS. Recent evidence suggests that epigenetic mechanisms, which constitute molecular changes not driven by a change in gene sequence, can mediate environmental effects on central and peripheral function. Epigenetic alterations including DNA methylation changes, histone modifications, and differential expression of non-coding RNAs (microRNA [miRNA] and long non-coding RNA) have been associated with several diseases. The objective of this review is to elucidate the molecular factors in the pathophysiology of IBS with an emphasis on epigenetic mechanisms. Emerging evidence for epigenetic changes in IBS includes changes in DNA methylation in animal models of IBS and patients with IBS, and various miRNAs that have been associated with IBS and endophenotypes, such as increased visceral sensitivity and intestinal permeability. DNA methylation, in particular, is an emerging field in the realm of complex diseases and a promising mechanism which can provide important insights into IBS pathogenesis and identify potential targets for treatment.
Highlights
Irritable bowel syndrome (IBS) is a complex condition characterized by alterations of bidirectional brain-gut interactions affecting gastrointestinal (GI) function
We demonstrated that the presence of IBS was significantly associated with single nucleotide polymorphisms (SNPs) in corticotropin releasing hormone receptor 1 (CRH-R1) gene
We found that glucocorticoid receptors (GR) expression was decreased in peripheral blood mononuclear cells (PBMCs) in IBS patients in comparison to healthy controls and that GR expression levels negatively correlated with pituitary responsiveness (ACTH levels) to corticotropin releasing factor (CRF) stimulation [69]
Summary
Irritable bowel syndrome (IBS) is a complex condition characterized by alterations of bidirectional brain-gut interactions affecting gastrointestinal (GI) function. It is a widely prevalent disorder affecting about 5% to 11% of general population and occurs in children and adults and in men and women it is considered a female-predominant condition. Hallmark symptoms include the presence of chronic or recurrent abdominal pain associated with altered bowel habits without underlying structural abnormalities [1,2,3,4]. Due to its high prevalence, recurrent nature of symptoms and a negative impact on health-related quality of life [6], IBS is associated with substantial cost to patients, the health care system, and society [7]
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