Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut–brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.

Investigating Causal Associations Among Gut Microbiota, Metabolites, and Irritable Bowel Syndrome: A Mendelian Randomization Study

“…Short-chain fatty acids (SCFAs) are mainly composed of acetic acid, propionic acid, and butyric acid, which play a crucial role in the gut (54). A recent systematic review and metaanalysis revealed that compared with healthy controls the levels of propionic acid and butyric acid were decreased in IBS-C patients, while the level of butyric acid was increased in IBS-D patients (55). The metabolism of bile acids (BAs) may be to do with IBS, and it has been demonstrated that the level of BAs was related to visceral pain and colon transit.…”

Metagenomics and metabolomics analysis to investigate the effect of Shugan decoction on intestinal microbiota in irritable bowel syndrome rats

“…Notably, Bile secretion can regulate visceral pain perception and improve visceral hypersensitivity in IBS patients ( Ní Dhonnabháín et al, 2021 ). The increased expression of bile acid in fecal, primary bile acid in liver and bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) in colon in most patients with IBS-D is closely related to the severity of diarrhea symptoms ( Walters, 2021 ; Wei et al, 2021 ), and the TGR5-ECS-5-HT signaling pathway may play an important role in the pathophysiology of IBS ( Tao et al, 2022 ). Bile acids can control the circadian variation of the metabolite uric acid through the regulation of xanthine oxidase by PPARα ( Kanemitsu et al, 2017 ).…”

The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome

“…When EC cells ar exposed to intraluminal pressure or chemical and mechanical stimulation, serotonin i released either apically to the gut lumen or basolaterally to the lamina propria. Upon it release, serotonin may take several possible routes, including having a direct influence on the gut microbiota, exerting influence on intracellular signaling by acting on 5-HT recep tors (5-HTRs), or being reuptook by surrounding epithelial and immune cells via the ser otonin reuptake transporter (SERT, encoded by the SLC6A4 gene), or entering the blood In blood, serotonin is present as free serotonin or it is taken up by platelets via SERT (ap proximately 95%) [57,58]. Any excess serotonin in the cells is degraded by monoamin oxidase (MAO), resulting in the production of 5-hydroxyindoleacetic acid (5-HIAA) which is mainly excreted in urine.…”