Postnatal and diet‐dependent increases in enteric glial cells and VIP‐containing neurones in preterm pigs

Abstract

A mature enteric nervous system (ENS) is required to ensure a normal pattern of intestinal motility in order to regulate digestion after birth. We hypothesized that neuronal and glial components of the ENS would mature during the first postnatal days in preterm pigs that are a sensitive animal model of food intolerance and necrotizing enterocolitis (NEC). Stereological volume densities of the general neuronal population [assessed by betaIII-tubulin immunoreactivity (IR)] and subsets of neuronal (VIP-IR and nitrergic IR) and glial cells (GFAP-IR and S100-IR) were determined in the small intestine of newborn preterm piglets (93% gestation), after 3 days of receiving total parenteral nutrition (TPN) and after 3 days of TPN plus 2 days of enteral feeding with sow's colostrum or milk formula. Following TPN, VIP in the myenteric and inner submucous plexus and GFAP in the inner submucous plexus increased, while the relative volume of the total neuronal population remained constant. Introduction of enteral food induced variable degrees of food intolerance and NEC, especially after formula feeding, a diet that gave rise to a higher myenteric VIP and GFAP content in the inner submucous plexus than colostrum feeding. However, the ENS seemed unaffected by the presence of NEC-like intestinal lesions. Nevertheless, this study shows that the ENS is highly plastic during the first days after premature birth and adapts in an age- and diet-dependent manner. The observed postnatal adaptation in enteric VIP and GFAP may help to maintain intestinal homeostasis during suboptimal feeding regimens in preterm neonates.

Enteric Glial Cells: Recent Developments and Future Directions

“…Short-chain fatty acids have indeed been shown to enhance enteric neuronal maturation. 10 Early life changes in nutrient composition have also been shown to enhance GFAP expression in a model of neonatal pig, 11 and administration of a high-fat diet has been shown to increase the number of EGCs in juvenile mice. 12…”

Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

“…Mucosal colonization density increases immediately following the transition to enteral feeding, particularly using formula (relative to colostrum), facilitating a pronounced Gram-negative proinflammatory (IL-1β) state of the preterm intestine. This initial proinflammatory insult after TPN may then subsequently affect regulators of small intestinal motility and tissue perfusion as indicated by the formula-induced adaptational increases in glial cell density, as well as neuronal nitric oxide synthetase (nNOS)-and vasoactive intestinal peptide (VIP)-containing neurons [119,120]. Although the feeding-induced decrease in endothelial nitric oxide synthetase, reflecting maladaptation of the intestinal microvasculature, is relatively diet-independent, only formula-fed pigs show increased hypoxia sensitivity, as indicated by hypoxia-inducible factor-1 alpha (HIF-1α) expression [121] (Fig.…”

Emerging roles for enteric glia in gastrointestinal disorders

“…However, studies examining the effects of dietary manipulation and aging reveal that enteric glial cell numbers appear to be influenced by both age and diet, suggesting that environmental factors are able to influence glial cell numbers (28,(42)(43)(44)(45)(46). Studies of aging reveal a consistent reduction in enteric glial cell density in the myenteric plexus (28,44).…”