Enteroendocrine cell regulation of the gut-brain axis

Abstract

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, and even information from our microbiome. EECs are hormone-producing cells expressed throughout the gastrointestinal epithelium and have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), and retatrutide (Phase 2) for diabetes and weight control, and linaclotide (Linzess) to treat irritable bowel syndrome (IBS) and visceral pain. This review focuses on role of intestinal EECs to communicate signals from the gut lumen to the brain. Canonically, EECs communicate information about the intestinal environment through a variety of hormones, dividing EECs into separate classes based on the hormone each cell type secretes. Recent studies have revealed more diverse hormone profiles and communication modalities for EECs including direct synaptic communication with peripheral neurons. EECs known as neuropod cells rapidly relay signals from gut to brain via a direct communication with vagal and primary sensory neurons. Further, this review discusses the complex information processing machinery within EECs, including receptors that transduce intraluminal signals and the ion channel complement that govern initiation and propagation of these signals. Deeper understanding of EEC physiology is necessary to safely treat devastating and pervasive conditions like irritable bowel syndrome and obesity.

Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

“…This summary underscores the critical importance and urgency of using probiotics and advancing research related to cognitive aging. Ongoing studies aim to deepen our understanding of the interactions within the microbiome–gut–brain axis, particularly exploring mechanisms between the gastrointestinal tract and the nervous system [ 122 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 ]. Future research should focus on more precise analyses and explorations of the composition of gut microbiota, identifying which strains are dominantly associated with conditions such as anxiety, depression, Parkinson’s disease, and other psychiatric and cognitive disorders, including Alzheimer’s disease [ 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 ].…”

Mind, Mood and Microbiota—Gut–Brain Axis in Psychiatric Disorders

“…The gut microbiota modulates nutrient availability, thereby impacting the secretion of biologically active peptides from enteroendocrine cells. This alteration in peptide release can subsequently influence the functioning of the gut–brain axis [ 22 ]. Therefore, the neuropeptide galanin enhances the activity of the central component of the HPA axis, influencing the secretion of corticotropin-releasing factors (CRFs) and ACTHs.…”

The Impact of Early-Life Cecal Microbiota Transplantation on Social Stress and Injurious Behaviors in Egg-Laying Chickens

“…The gut microbiota plays a critical role in early programming and later activity of the central stress systems, i.e., the hypothalamic–pituitary–adrenal (HPA) and the sympathetic–adrenal–medullary (SAM) axes [ 52 , 53 , 54 ]. Like an endocrine organ, the gut microbiota is sensitive and reactive to various exogenous stimuli, functioning as an environmental sensor linked to the pathogenesis of stress-related illnesses through the bidirectional communication of the MGB axis [ 55 , 56 , 57 , 58 , 59 ] and the microbiota–gut–immune (MGI) axis [ 60 , 61 ] in various animals including chickens [ 62 , 63 , 64 ].…”