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.

Innate Lymphoid Cells in Crohn’s Disease

“…Additionally, the release of these cytokines can also change the intestinal flora ( 12 ). ILCs may link the intestinal flora and ENS and work together in the intestine ( 116 , 117 ).…”

Innate Lymphoid Cells: A Link between the Nervous System and Microbiota in Intestinal Networks

“…The release of these cytokines can also alter the gut microbiota. Several reports have also suggested links between the gut microbiota and ENS, potentially involving ILCs [100, 101].…”

The Impact of Starvation on the Microbiome and Gut-Brain Interaction in Anorexia Nervosa

“…Contact with different bacteria, depending on our mode of birth, i.e., vaginally or via C-section, and whether we were breastfed strongly influence which bacteria inhabit our gastrointestinal tract, with probably lifelong consequences for our immune system (62). The number of metabolic and neurologic diseases with altered gut microbiome and evidence for gut-brain interactions is constantly rising (63): In type 2 diabetes the microbiome appears to disturb the enteric nervous system via inflammatory processes, impairing its role in informing the hypothalamus of the nutritional state to properly control glucose entry in tissues (64, 65). In Parkinson's disease, α-Synuclein aggregates, the major neuropathologic marker of the disease, are detectable in the enteric nervous system prior to the brain, with a possible gut to brain prion-like transmission (66); abundance of Prevotellaceae is reduced by 80%, and abundance of Enterobacteriaceae was highly correlated with postural instability and gait difficulty (67).…”