Inflammation and Gut-Brain Axis During Type 2 Diabetes: Focus on the Crosstalk Between Intestinal Immune Cells and Enteric Nervous System

Abstract

The gut-brain axis is now considered as a major actor in the control of glycemia. Recent discoveries show that the enteric nervous system (ENS) informs the hypothalamus of the nutritional state in order to control glucose entry in tissues. During type 2 diabetes (T2D), this way of communication is completely disturbed leading to the establishment of hyperglycemia and insulin-resistance. Indeed, the ENS neurons are largely targeted by nutrients (e.g., lipids, peptides) but also by inflammatory factors from different origin (i.e., host cells and gut microbiota). Inflammation, and more particularly in the intestine, contributes to the development of numerous pathologies such as intestinal bowel diseases, Parkinson diseases and T2D. Therefore, targeting the couple ENS/inflammation could represent an attractive therapeutic solution to treat metabolic diseases. In this review, we focus on the role of the crosstalk between intestinal immune cells and ENS neurons in the control of glycemia. In addition, given the growing evidence showing the key role of the gut microbiota in physiology, we will also briefly discuss its potential contribution and role on the immune and neuronal systems.

Keywords: diabetes; enteric nervous system; gut-brain axis; immune cells; microbiota.

FIGURE 1

Modulation of the enteric nervous system activity by intestinal immune system may impact on glycemia regulation. Most microbiota-derived products activate both epithelial cells and innate immune cells through pathogen recognition receptors such as toll-like receptors. They also initiate, mainly via microbe sampling through M(icrofold) cells, an adaptive immune response. This physiological immune response against intestinal flora generating pro-inflammatory effector T lymhocytes is tighly regulated by regulatory T lymphocytes which induction is associated with the production of short chain fatty acids (SCFAs) by commensal bacteria. Failure of the immune homeostasis may result in the release of higher amounts of proinflammatory cytokines including TNFα, IL1-β, IL6, IFNγ which, in turn, modulate either directly or through glial cells, enteric nervous system (ENS) activity. These alterations of the ENS contribute to impair gut-brain-peripheral axis leading to hyperglycemia and insulin-resistance.