Gut microbiota–5-hydroxytryptamine–intestinal motility axis (Gut microbiota–5-HT–motility axis)

The gut microbiota–5-hydroxytryptamine (5-HT)–intestinal motility axis is a complex physiological system that coordinates gastrointestinal function through interactions between the microbiome, enterochromaffin cells, and the enteric nervous system. Approximately 90% of the body's serotonin is synthesized in the gut by enterochromaffin cells, a process regulated by microbial metabolites such as short-chain fatty acids and secondary bile acids (Yano et al., 2015). This locally produced 5-HT acts as a critical signaling molecule, binding to 5-HT3 and 5-HT4 receptors on intrinsic primary afferent neurons to initiate and maintain the peristaltic reflex (Gershon, 2013). Dysregulation of this axis, often resulting from gut dysbiosis, is a primary driver of functional gastrointestinal disorders, including irritable bowel syndrome (IBS) and chronic constipation (Ge et al., 2018). Therapeutic interventions targeting this axis include 5-HT4 receptor agonists to accelerate transit and 5-HT3 receptor antagonists to slow motility and reduce visceral hypersensitivity (Enck et al., 2016). Additionally, probiotics and prebiotics are increasingly utilized to modulate the microbial component of the axis to restore normal serotonergic signaling and bowel habits (Cao et al., 2021).

Other names

Microbiota-gut-brain axisGut-brain axisSerotonergic signaling axisMicrobiome-5-HT-motility pathway

Modulation of serotonin receptors (5-HT3, 5-HT4), inhibition of the serotonin transporter (SERT), and microbial-mediated stimulation of enterochromaffin cell serotonin production.