Novel aspects of enteric serotonergic signaling in health and brain-gut disease

Abstract

Gastrointestinal (GI) comorbidities are common in individuals with mood and behavioral dysfunction. Similarly, patients with GI problems more commonly suffer from co-morbid psychiatric diagnoses. Although the central and enteric nervous systems (CNS and ENS, respectively) have largely been studied separately, there is emerging interest in factors that may contribute to disease states involving both systems. There is strong evidence to suggest that serotonin may be an important contributor to these brain-gut conditions. Serotonin has long been recognized for its critical functions in CNS development and function. The majority of the body’s serotonin, however, is produced in the GI tract, where it plays key roles in ENS development and function. Further understanding of the specific impact that enteric serotonin has on brain-gut disease may lay the foundation for the creation of novel therapeutic targets. This review summarizes the current data focusing on the important roles that serotonin plays in ENS development and motility, with a focus on novel aspects of serotonergic signaling in medical conditions in which CNS and ENS co-morbidities are common, including autism spectrum disorders and depression.

Bioaminergic Responses in an In Vitro System Studying Human Gut Microbiota–Kiwifruit Interactions

“…The TPH gene expresses the rate-limiting enzyme for 5-HT biosynthesis, of which the TPH1 isoform is located in the gut epithelial cells as well as the enterochromaffin cells, while TPH2 gene is expressed only in neuronal cells of the gut and the brain [ 53 , 54 ]. Serotonin has many beneficial roles in gut motility and innate immunity, but in excess may mediate pro-inflammatory states by sending quorum sensing signals that enhance bacterial pathogenicity [ 18 ].…”

“…Microbiota-mediated enteric bioaminergic signaling may influence the integrity of the intestinal epithelium, compromise of which has been associated with inflammation [ 22 , 53 ]. The increase in the expression of CLDN4 , which expresses the claudin4 tight junction protein, with fermenta may imply a role for microbial metabolites in modulating the gut wall physicochemical structure.…”

Alterations in Gut Vitamins and Amino Acids Metabolism are Associated with Symptoms and Neurodevelopment of Children with Autism Spectrum Disorders

“…An experiment in mice model of autism found a decrease of serotonin in intestine mucosal [39]. However, given 95% of the serotonin in body is generated in the intestine [40], it is likely that blood serotonin levels are correlated with enteric serotonin. Likewise, gastrointestinal tract are also important source of melatonin besides the pineal gland [41].…”

The Vegetative Receptor-Vascular Reflex (VRVR) – A New Key to Regeneration

“…It has been only recently that brain researchers have pointed to the importance of the vegetative and unconscious elements of our nervous system for our consciousness (Damasio, 2000). And even more recent is the interest in the connection between the enteric nervous system and the central nervous system (Mayer, 2011;Del Colle et al, 2019;Osadchiy et al, 2019;Iseger et al, 2020).…”