Emerging Roles of Gut Serotonin in Regulation of Immune Response, Microbiota Composition and Intestinal Inflammation

• Published in: Journal of the Canadian Association of Gastroenterology Vol. 7; no. 1; pp. 88 - 96
• Main Authors: Grondin, Jensine A, Khan, Waliul I
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.02.2024
• ISSN: 2515-2084; 2515-2092
• DOI: 10.1093/jcag/gwad020

Abstract Although the exact etiology of inflammatory bowel diseases (IBD) is unknown, studies have shown that dysregulated immune responses, genetic factors, gut microbiota, and environmental factors contribute to their pathogenesis. Intriguingly, serotonin (5-hydroxytryptamine or 5-HT) seems to be a molecule with increasingly strong implications in the pathogenesis of intestinal inflammation, affecting host physiology, including autophagy and immune responses, as well as microbial composition and function. 5-HT may also play a role in mediating how environmental effects impact outcomes in IBD. In this review, we aim to explore the production and important functions of 5-HT, including its impact on the gut. In addition, we highlight the bidirectional impacts of 5-HT on the immune system, the gut microbiota, and the process of autophagy and how these effects contribute to the manifestation of intestinal inflammation. We also explore recent findings connecting 5-HT signalling and the influence of environmental factors, particularly diet, in the pathogenesis of IBD. Ultimately, we explore the pleiotropic effects of this ancient molecule on biology and health in the context of intestinal inflammation. Lay Summary The term inflammatory bowel disease (IBD) refers to numerous conditions, including Crohn’s disease and ulcerative colitis. IBD is characterized by reoccurring inflammation in the gastrointestinal tract. Research suggests that serotonin (5-hydroxytryptamine or 5-HT), a molecule best known as a neurotransmitter in the brain, has a strong impact on the development of intestinal inflammation. 5-HT can alter the body’s ability to recycle damaged compounds within cells in a process known as autophagy. It can also affect gut bacteria and the functions of the immune system. In addition, 5-HT may play a role in how the body responds to environmental factors such as diet. In this review, we explore how 5-HT is produced and how it functions in the gut. We highlight its effects on the immune system and gut microbes, and how these changes contribute to gut inflammation. Additionally, we look at recent findings which suggest 5-HT may be a key molecule in how environmental factors, like diet, contribute to IBD. Ultimately, we explore how this ancient molecule affects health and biology in the context of intestinal inflammation.