Enterochromaffin Cells–Gut Microbiota Crosstalk: Underpinning the Symptoms, Pathogenesis, and Pharmacotherapy in Disorders of Gut-Brain Interaction

Lai Wei; Rajan Singh; Uday C Ghoshal

doi:10.5056/jnm22008

J Neurogastroenterol Motil https://doi.org/10.5056/jnm22008

Enterochromaffin Cells–Gut Microbiota Crosstalk: Underpinning the Symptoms, Pathogenesis, and Pharmacotherapy in Disorders of Gut-Brain Interaction

Lai Wei

,¹ Rajan Singh

,² and Uday C Ghoshal

^3*

¹Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA; ²Department of Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, NV, USA; and ³Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Correspondence to: Uday C Ghoshal, MD, DNB, DM, FACG, RFF, FAMS, FRCP
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow, 226014, India
Tel: +91-522-2494405, Fax: +91-522-2668017, E-mail: udayghoshal@gmail.com

Received: January 17, 2022; Revised: March 16, 2022; Accepted: April 4, 2022; Published online: June 20, 2022

Abstract: Disorders of gut-brain interaction (DGBIs) are common conditions in community and clinical practice. As specialized enteroendocrine cells, enterochromaffin (EC) cells produce up to 95% of total body serotonin and coordinate luminal and basolateral communication in the gastrointestinal (GI) tract. EC cells affect a broad range of gut physiological processes, such as motility, absorption, secretion, chemo/mechanosensation, and pathologies, including visceral hypersensitivity, immune dysfunction, and impaired gastrointestinal barrier function. We aim to review EC cell and serotonin-mediated physiology and pathophysiology with particular emphasis on DGBIs. We explored the knowledge gap and attempted to suggest new perspectives of physiological and pathophysiological insights of DGBIs, such as (1) functional heterogeneity of regionally distributed EC cells throughout the entire GI tract; (2) potential pathophysiological mechanisms mediated by EC cell defect in DGBIs; (3) cellular and molecular mechanisms characterizing EC cells and gut microbiota bidirectional communication; (4) differential modulation of EC cells through GI segment-specific gut microbiota; (5) uncover whether crosstalk between EC cells and (i) luminal contents; (ii) enteric nervous system; and (iii) central nervous system are core mechanisms modulating gut-brain homeostasis; and (6) explore the therapeutic modalities for physiological and pathophysiological mechanisms mediated through EC cells. Insights discussed in this review will fuel the conception and realization of pathophysiological mechanisms and therapeutic clues to improve the management and clinical care of DGBIs.; Keywords: Enterochromaffin cells; Gastrointestinal microbiome; Gut barrier dysfunction; Gastroparesis; Irritable bowel syndrome