Epigenetic Mechanisms in Irritable Bowel Syndrome

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 hypothalamuspituitary-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.

Psychological Distress Among HIV Healthcare Providers During the COVID-19 Pandemic in China: Mediating Roles of Institutional Support and Resilience

“…This finding provided a novel insight regarding COVID-19 stress management at HIV clinics, particularly on the importance of institutional support. Previous studies showed that healthcare providers in supportive working environments were inclined to exhibit greater resilience-related abilities, including emotional regulation [ 47 ], self-efficacy [ 48 ], and adaptive coping strategies [ 49 ]. In facing a public health emergency, sufficient institutional support might enable HIV healthcare providers to use their internal coping recourses (i.e., resilience) and facilitate providers’ adaptive coping instead of being overwhelmed to deal with COVID-19 stressors, resulting in reduced levels of distress.…”

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome

“…79 There is some evidence for epigenetic changes in IBS, including alterations in DNA methylation, and various miRNAs appear to be associated with increased visceral sensitivity and permeability. 80…”

Role of microRNAs in Disorders of Gut–Brain Interactions: Clinical Insights and Therapeutic Alternatives

“…Previous studies evidenced that loss of functional activity of the GI pacemaking cells including, ICCs, SMCs, enteric neurons, platelet-derived growth factor receptor alpha positive (PDGFRα + ), and immune cells are driving forces contributing to the pathogenesis of DGBIs [10,23,29,31,50]. Cellular dysfunction in GI cells mediated via dysregulation of miRNAs likely regulates a variety of gut physiological and pathophysiological mechanisms leading to the development of diseases such as DGBIs [51,52]. Approximately 60% of protein coding mRNAs are modulated by miRNAs, including many of the key proteins associated with diseases [41,53].…”