Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention

Abstract

Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene-environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome.

Muscularis macrophage development in the absence of an enteric nervous system

“…In rodents the proportion of cholinergic neurons increases until P36 (33), and some enteric neurons do not obtain mature dendritic and electrophysiological properties until adulthood (34). Various environmental signals, such as intraluminal lipid and bacterial exposure, also impact postnatal enteric neuron plasticity and signaling (1,4,5,35,36) and may have important roles in shaping neuro-immune circuits in the bowel.…”

Association between miR-492 rs2289030 G>C and susceptibility to Hirschsprung disease in southern Chinese children

“… 59 – 61 This inconsistency between studies may be attributed to genetic variations and living environments between different ethnic groups. 62 Because of the possible differences in allele frequencies and SNP linkage imbalance patterns among different populations, only the rs2289030 C>G SNP from the miR-492 gene was selected for association analysis in the current study. More gene polymorphisms should be further investigated in the future.…”

An intravital window to image the colon in real time

“…Enteric neurons have been proposed to have a fast turnover rate compared to neurons in the central nervous system. This imaging technology can monitor enteric neuron development and turnover 72 , which can be a useful technique for analyzing disease models like Hirschsprung's disease, to monitor aganglionosis in the distal colon 73,74 . While in vitro and ex vivo experiments provide useful data regarding ENS dynamics 75,76 , it is more physiologically relevant to monitor the ENS in vivo in which extrinsic pathways are intact and the ENS can interact with immune cells, enteroendocrine cells, and others 49,[77][78][79][80] .…”