Peripheral serotonin: cultivating companionship with gut microbiota in intestinal homeostasis

Am J Physiol Cell Physiol. 2022 Aug 1;323(2):C550-C555. doi: 10.1152/ajpcell.00433.2021. Epub 2022 Jun 27.

Abstract

Serotonin, also known as 5-hydroxytryptamine (5-HT), is an evolutionarily ancient and phylogenetically conserved monoamine that regulates multifaceted physiological functions in mammals. 5-HT was, at one time, most extensively studied as a neurotransmitter within the central nervous system but is now known to regulate nonneuronal functions including immune responses in an autocrine-paracrine-endocrine manner. Compelling evidence from intervention studies using germ-free mice or antibiotic-associated microbiota perturbation suggests that novel interactions between 5-HT and the gut microbiota are essential in maintaining intestinal homeostasis. Importantly, recent studies reveal that bidirectional host-microbial interactions mediated by the host serotonergic system can promote distinct changes within the gut microbiota. These changes may potentially lead to a state known as "dysbiosis" that has been strongly associated with various gut pathologies including inflammatory bowel disease (IBD). In this review, we update the current understanding of host-microbiota interaction by focusing on the impact of peripheral 5-HT signaling within this dynamic. We also briefly highlight key environmental risk factors for IBD, such as the Western diet, and draw attention to the interaction of synthetic food colorants with 5-HT signaling that may facilitate future research.

Keywords: 5-HT; enterochromaffin cells; intestine; microbiota; serotonin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gastrointestinal Microbiome*
  • Homeostasis
  • Host Microbial Interactions
  • Inflammatory Bowel Diseases*
  • Mammals
  • Mice
  • Serotonin

Substances

  • Serotonin