Postnatal development of the myenteric glial network and its modulation by butyrate

Abstract

The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fatty acids on their maturation. We showed an increased expression of the glial markers GFAP and S100β during the first postnatal week. As demonstrated by immunohistochemistry, a structured myenteric glial network was observed at 36 days in the rat colons. Butyrate inhibited EGC proliferation in vivo and in vitro but had no effect on glial marker expression. These results indicate that the EGC myenteric network continues to develop after birth, and luminal factors such as butyrate endogenously produced in the colon may affect this development.

Butyrate promotes visceral hypersensitivity in an IBS‐like model via enteric glial cell‐derived nerve growth factor

“…These observations were in agreement with previous studies that butyrate could affect function of EGC, which was shown to be intimately correlated with neuronal maturation. 33 Neurotrophins were identified as crucial factors in regulating neuronal development and function.…”

The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System

“…Of note, the butyrate-induced increase in excitatory choline acetyltransferase (ChAT)+ neurons depended on the butyrate transporter monocarboxylate transporter (MCT)2, which is expressed by enteric neurons, 51 but the factors regulating neuronal MCT2 expression remain unknown. A recent study has shown that the EGC cell line, JUG-2, also expresses MCT1 and MCT2, 53 although the physiological role of these enzymes on glial homeostasis in vivo has not been determined.…”

“…The epigenetic regulation of the immune system by gut microbial butyrate has been shown in colonic T cells39, 65 and macrophages 66 . Although little is known about the epigenetic modifications of ENS by SCFAs, butyrate treatment enhances acetylation of the H3K9 in primary cultured enteric neurons and the EGC cell line JUG-2 51, 53. It would be interesting to determine the extent to which microbiota-derived SCFAs modulate the epigenetic status of genes and its role in enteric neurogenesis and gliogenesis.…”

Impaired intestinal barrier function and relapsing digestive disease: Lessons from a porcine model of early life stress

“…[33][34][35][36] Enteric glial cells form a dense network in the lamina propria in close proximity to intestinal epithelial cells, and we know that this network continues development into the postnatal period. [37][38][39] Preliminary work from our laboratory has shown that the number of glial cells and the relative extent of the glial cells network appear to be reduced in neonatal pigs as compared to older animals.…”

“…This is achieved by enteric glial cell release of paracrine factors such as glial-derived neurotrophic factor, pro-epidermal growth factor, 11β prostaglandin F 2α and S -nitrosoglutathione 33–36 . Enteric glial cells form a dense network in the lamina propria in close proximity to intestinal epithelial cells, and we know that this network continues development into the postnatal period 37–39 . Preliminary work from our lab has shown that the the number of glial cells and the relative extent of the glial cells network appears to be reduced in neonatal pigs as compared to older animals.…”