Tryptophan biosynthesis pathway in human microbiome and disease

Inhibition of tryptophan biosynthetic pathway and associated tryptophanyl-tRNA synthetase can effectively arrest growth of different microbial pathogens including bacteria and yeasts. The repression of amino acid permeases may prevent the tryptophan complementation from an environment such as the human gut that can provide the source for tryptophan uptake. The possibility of tryptophan movement with the concentration gradient (in other words, passive diffusion) from human compartments to human microbiome should be considered in prospective drug development based on the inhibition of tryptophan biosynthesis. The fecal tryptamine was significantly increased (2.62-fold) in hemodialysis patients versus controls. The benzoate metabolite hippuric acid was higher 33.25-fold in sera of hemodialysis patients versus controls. Fecal amino acids were significantly higher in the hemodialysis patients compared to controls: tryptophan (3.25-fold), tyrosine (3.66-fold), histidine (8.39-fold), and methionine (3.03-fold).