Diet and nerves: the impact of maternal feeding on newborn intestinal permeability

Abstract

Development during the postnatal period is critical for establishment of normal physiology of the intestinal tract, including permeability, the microbiota and intestinal defences. It is now well established that maternal factors also have a major impact on the development of intestinal physiology in developing neonates. Exposure to stress, via maternal separation, in rats leads to increased colonic barrier dysfunction, an altered secretory state and changes in host–microbial interactions (Gareau et al. 2006). Such dysfunctions occur in the presence of altered cholinergic nerves (Gareau et al. 2007b), and are normalized by either the administration of beneficial microbes, referred to as probiotics (Gareau et al. 2007a), or treatment with a non-selective corticotropin-releasing factor (CRF) antagonist (Gareau et al. 2006). Nutritional supplementation of neonatal rats during psychological stress improves both intestinal permeability and gut physiology (Garcia-Rodenas et al. 2006). Taken together, these studies highlight the link between neonatal diet, enteric nerves and the establishment of intestinal barrier function, although the contribution of nutrition to the dam was not addressed. Nutritional changes leading to altered neuronal composition during early life may well have long-term impacts on intestinal development and function. In the current issue of The Journal of Physiology, De Quelen et al. (2011) demonstrate that altering the maternal diet, as opposed to neonatal nutritional supplementation, impacts on the development of barrier function via changes to enteric nerves in piglets. This study extends previous findings by the same group, which demonstrated that linseed oil supplementation in the maternal diet during gestation and lactation could modify fatty acid composition, structure and physiology of neonatal ileum (Boudry et al. 2009). Establishment of barrier function early in life is important for appropriate development of the immune system, with elevated permeability in neonates thought to allow passage of macromolecules and other antigens required for development and maturation of the mucosal immune system. Maternal supplementation with polyunsaturated fatty acids (PUFAs) was able to modulate enteric nerve plasticity, resulting in proportional changes in the expression of vasoactive intestinal peptide (VIP) (decreases) and choline acetyltransferase (ChAT) (increases) positive neurons during development. These changes were observed despite the absence of physical changes to the epithelium, including crypt depth and villus height. Decreased barrier function, resulting from maternal supplementation, was thought to be maintained by altered expression of intercellular tight junction proteins (specifically ZO-1), although localization of such proteins was not established. Disruption of barrier function was not at the expense of the development of an altered immune response, as jejunal samples demonstrated similar cytokine levels in piglets independent of the type of maternal diet. While it is not clear whether such changes persist beyond weaning, the findings raise interesting questions about the impact of the maternal diet on the development of the intestinal tract and mucosal immune system of the progeny. The observed alteration to neuroplasticity by maternal diet is a novel and interesting concept, with implications reaching beyond the establishment of barrier function. For example, the impact of neurochemical changes on either gut motility or visceral sensitivity, both of which are thought to be regulated, at least in part by enteric nerves, would provide interesting and relevant follow-up studies. Furthermore, it would be interesting to determine whether the nutritional changes mediating neuron plasticity are also directly affecting the establishment of the gut microbiota in the neonate. Moreover, how the maternal diet influences these changes and transmits such information to the neonate remains to be addressed. Specifically, does diet change the maternal microflora that is then passed on to the pup, or is there a potential role for bacterial metabolites (for example, short-chain fatty acids, including butyrate) in regulating the observed changes. The in vitro experiments performed using neurons grown in culture indicate that the effects of PUFA supplementation on neuroplasticity are, at least in part, a direct effect of the nutritional treatment. Taken together, these studies clearly demonstrate that maternal nutritional supplementation with PUFA can impact enteric neuronal plasticity in neonatal piglets, which leads to alterations in gut permeability. These changes may well have long-term consequences on intestinal physiology and pathophysiology.