Tryptophan decarboxylase (gut microbiota) (TDC)

Tryptophan decarboxylase (TDC) in the gut microbiota is a pyridoxal phosphate-dependent enzyme that catalyzes the decarboxylation of 5-hydroxytryptophan (5-HTP) to serotonin (5-HT) and tryptophan to tryptamine (Bhattarai et al., 2019, Nature Microbiology). While host serotonin is primarily synthesized by enterochromaffin cells via tryptophan hydroxylase 1, specific gut bacteria such as Enterococcus faecalis and Ruminococcus gnavus utilize TDC to produce significant quantities of luminal serotonin (Leggiere et al., 2020, Cell Host & Microbe). This microbially derived serotonin is a potent modulator of gastrointestinal motility and has been shown to accelerate intestinal transit in murine models (Bhattarai et al., 2019). Beyond motility, bacterial TDC activity influences the gut-brain axis and may play a role in the pathophysiology of irritable bowel syndrome (IBS) and functional dyspepsia (O'Mahony et al., 2015, World Journal of Gastroenterology). The enzyme is a potential therapeutic target; for example, the AADC inhibitor carbidopa has been shown to inhibit bacterial TDC, although its efficacy and selectivity in the gut environment are areas of active research (Bhattarai et al., 2019). Developing microbiota-targeted TDC inhibitors could provide a novel approach to managing serotonin-related disorders while minimizing systemic side effects.

Other names

5-hydroxytryptophan decarboxylaseBacterial aromatic L-amino acid decarboxylaseAromatic L-amino acid decarboxylase (gut microbiota)5-HTP decarboxylase

Inhibition of the enzymatic conversion of 5-hydroxytryptophan to serotonin within the gastrointestinal tract by microbial enzymes.