Impact of Gut Microbiota Metabolites on Serotonin Levels in Irritable Bowel Syndrome

Gut microbiota and their metabolites have been proposed as possible etiological factors in irritable bowel syndrome (IBS), and studies suggest that IBS is associated with impaired serotonin synthesis and release. Microbial metabolites are produced through biological pathways and enzymatic processes via gut microbiota. Gut bacteria generate a range of metabolites, including short‐chain fatty acids (SCFAs), bile acids, tryptophan (Trp), hypoxanthine, vitamins, and neurotransmitters. Various classical neurotransmitters and neuropeptides may influence the serotonin secretion and modulate TPH1 expression, and similar effects have been reported in microbial metabolites. Many of these metabolites are thought to act through GPCRs expressed in enteroendocrine (EE) cells, although the strength of evidence varies by the metabolite and experimental model. Current preclinical and cellular studies suggest that microbial metabolites may be sensed after, or during, absorption through receptors expressed on the basolateral membrane of enterochromaffin (EC) cells. These synapses are formed by gut sensory epithelial cells called neuropod cells. As studies indicated that neuropod cells play a fundamental role in perceiving microbiota metabolites and could serve as future targets for regulating metabolite‐mediated functions. From the intestinal condition to the brain, neuropod cells act as the gut foundation to transduce sensory signals through fast neurotransmission onto neurons, including the vagus nerve. Investigation of the underlying mechanisms on interactions between serotonin and microbial metabolites may advance our understanding regarding the pathology of IBS.