Perinatal nutrition programs neuroimmune function long-term: mechanisms and implications

Abstract

Our early life nutritional environment can influence several aspects of physiology, including our propensity to become obese. There is now evidence to suggest perinatal diet can also independently influence development of our innate immune system. This review will address three not-necessarily-exclusive mechanisms by which perinatal nutrition can program neuroimmune function long-term: by predisposing the individual to obesity, by altering the gut microbiota, and by inducing epigenetic modifications that alter gene transcription throughout life.

Keywords: epigenetics; glucorticoids; gut microbiota; hypothalamic-pituitary-adrenal axis; obesity.

Figure 1

Perinatal diet may influence glucocorticoid negative feedback following immune challenge. (A) Pathogens such as lipopolysaccharide act at toll-like receptors (e.g., TLR4) on immune cells leading to phosphorylation of inhibitory factor (I)κ B, releasing nuclear factor (NF)κ B from its complex and allowing it to be translocated to the nucleus. NKκ B is responsible for the transcription of pro- and anti-inflammatory cytokines, the former of which stimulate the cyclo-oxygenase 2-mediated conversion of aracidonic acid into prostaglandins. Prostaglandins (e.g., PGE2) act at the brain to stimulate fever and sickness behavior and recruit the HPA axis. Once released, glucocorticoids (GC) negatively feed back to inhibit further NFκ B-mediated transcription of cytokines. (B) The perinatal diet may influence glucocorticoid negative feedback by altering expression of glucocorticoid receptors (GR) in the hippocampus and hypothalamus leading to less efficient glucocorticoid-mediated inhibition of NFκ B and an exacerbated immune response.