IBS: an epigenetic perspective

Abstract

IBS is a common and debilitating disorder. The pathophysiology of IBS is poorly understood and is currently viewed as a biopsychosocial disorder with symptoms mediated via the brain-gut axis. Epidemiological studies of IBS point to risk factors such as familial clustering, sexual abuse and other forms of childhood trauma, low birth weight and gastrointestinal infection. Epigenetics focuses on the complex and dynamic interaction between the DNA sequence, DNA modifications and environmental factors, all of which combine to produce the phenotype. Studies in animal models of early stress and in humans who have experienced childhood trauma or abuse suggest that these events can lead to long-lasting epigenetic changes in the glucocorticoid receptor gene brought about by hypermethylation of a key regulatory component. Animal studies also indicate that the microbiota has a pivotal role in programming the core stress system, the hypothalamic-pituitary-adrenal axis and the immune system through epigenetic mechanisms. In this Perspectives, an epigenetic model of IBS is presented that incorporates many of the current findings regarding IBS, including proinflammatory markers, neuroendocrine alterations and links with both psychosocial stress and stress related to infection. We conclude that applying epigenetic methodology to this common and disabling disorder may help unravel its complex pathophysiology and lead to more effective treatments.

The Microbiome-Gut-Brain Axis in Health and Disease

“…IBS is the prototypic disorder of the brain-gut-microbiota axis, generally perceived as a having a biopsychosocial aetiology 36 However, the postprandial levels of total SCFAs, acetic acid, propionic acid, and butyric acid were found to be significantly lower in patients with IBS compared with healthy…”

Epidemiology of Functional Gastrointestinal Disorders in Japan and in the World

“…94 When the parents have IBS, the risk of the development of IBS in their children is high, and the concordance between mothers and children was greater than the concordance between monozygotic twins, 75 indicating that not only genetic factors, but also parental behaviors affect their children. 95 Childhood abuse is associated with the development and exacerbation of IBS and the development of dyspepsia. 24,[96][97][98] These are also environmental factors related to the development of FGIDs.…”

Impact of childhood maltreatment on physical health-related quality of life in U.S. active duty military personnel and combat veterans

“…Participants in this sample all had combat exposure and denied pre-deployment Axis I diagnosis, though these data were self-reported and participants may have had undiagnosed mental health conditions. Nonetheless, the association may lend support to epigenetic research on the cumulative impact of trauma on physical and mental health (Dinan, Cryan, Shanahan, Keeling, & Quigley, 2010;Nelson et al, 2009).…”