TITLE:
Scratching the Surface: Exploring Gastrointestinal Serotonin’s Impact on Chronic Pruritus in Irritable Bowel Syndrome and Dyspepsia
AUTHORS:
Alejandra Sataray-Rodriguez, Donia Javidi, Behzad Maher, Alyssa Forsyth, Muhammad Hassan, Alexandra Loperfito, Esther Nwozo
KEYWORDS:
Serotonin Dysregulation, Chronic Pruritus, Gut-Brain Axis, Irritable Bowel Syndrome, Functional Dyspepsia, Neurogenic Inflammation, Serotonin Receptor Modulators, Microbiota-Targeted Therapies
JOURNAL NAME:
Open Journal of Clinical Diagnostics,
Vol.15 No.1,
March
27,
2025
ABSTRACT: Background and Aims: Gastrointestinal-derived serotonin (5-HT) plays a crucial role in the enteric nervous system and has been identified as a key mediator in the pathogenesis of chronic pruritus associated with irritable bowel syndrome (IBS) and functional dyspepsia (FD). Dysregulated serotonin signaling, driven by altered enterochromaffin cell activity and abnormal serotonin reuptake, contributes to gut-brain axis dysfunction and sensitizes peripheral nerves, leading to increased pruritic sensations. This review explores the interplay between serotonin dysregulation, neurogenic inflammation, and chronic pruritus in IBS and FD, with an emphasis on potential therapeutic interventions. This review aims to address the gap in understanding the specific mechanisms by which serotonin dysregulation affects pruritus and gastrointestinal function, offering new insights into potential therapeutic approaches. Methods: A comprehensive literature review was conducted to examine the role of serotonin dysregulation in chronic pruritus associated with IBS and FD. Relevant studies were analyzed to assess serotonin’s impact on visceral hypersensitivity, systemic inflammation, and neurogenic skin responses. Additionally, the effectiveness of serotonin receptor modulators, systemic agents such as gabapentinoids, and microbiota-targeted therapies in mitigating pruritic symptoms was evaluated. Results: Dysregulated serotonin signaling in IBS and FD exacerbates visceral hypersensitivity and systemic inflammation, contributing to neurogenic inflammation in the skin and the release of pruritogenic mediators, including substance P and histamine. This persistent itch response significantly reduces patients’ quality of life. Evidence suggests that serotonin receptor modulators, particularly 5-HT3 and 5-HT4 antagonists, can alleviate pruritic symptoms by addressing both gastrointestinal motility and pruritus-associated pathways. Additionally, systemic agents like gabapentinoids provide complementary neural desensitization. Emerging data indicate that gut microbiome imbalances in IBS and FD influence serotonin production, highlighting a potential role for microbiota-targeted therapies in reducing pruritus severity. Conclusions: Addressing the complex interaction between gastrointestinal serotonin dysregulation, neurogenic inflammation, and chronic pruritus is essential for advancing therapeutic strategies. A comprehensive approach targeting the gut-brain-skin axis has the potential to redefine pruritus management and improve patient outcomes in IBS and FD. Future research should focus on optimizing serotonin-targeted therapies and exploring microbiota-based interventions to enhance treatment efficacy. This review highlights the novel contributions of serotonin modulation and microbiome-targeted therapies in treating pruritus and gastrointestinal conditions, offering a framework for future research in this integrated therapeutic area.