Susceptibility to stress-induced visceral sensitivity: a bad legacy for next generations

Abstract

Despite high prevalence, the precise irritable bowel syndrome (IBS) pathophysiology remains poorly understood likely due to the heterogeneity of IBS populations and the multifactorial etiology of this disorder. Among risk factors, genetic predisposition and early life trauma have been reported. In this context, the debate on genetic or environmental influences in the IBS pathogenesis is still open. The study by van der Wijngaard etal., reporting for the first time that susceptibility to stress-induced visceral hypersensitivity in maternally separated rats can be transferred to the next generation without any further exposure of F2 individuals to maternal separation, supports the importance of environmental influence in the IBS phenotype. Epigenetic mechanisms such as hypermethylation in the promoter region of the glucocorticoid receptor gene mediating the long-term and transgenerational behavioral effects of maternal care on the development have been shown in some but not in all studies. Van der Wijngaard etal. incriminated maternal care in the transmitted susceptibility to stress-induced visceral hypersensitivity, but not changes in glucocorticoid receptor protein expression in the brain. This finding opens a broad field of future directions aimed at evaluating the mechanisms involved in the transmission across generations of the digestive features of IBS, including, for example, on the role of gut microbiota changes in vertical transmission or epigenetic modifications of intestinal mast cells and the junctional region of intestinal epithelial cells in vertical transfer.