Fig. 6: Impacts on tryptophan metabolism mediated by dietary fibre and substrate.

In the gut, multiple bacterial species require tryptophan for their metabolism and produce bioactive molecules important for host health. E. coli catabolizes tryptophan into indole to generate pyruvate, while C. sporogenes regenerates NAD⁺ and produces ILA and IPA through the Stickland fermentation reductive pathway. The fibre degrader B. thetaiotaomicron degrades pectin and thereby releases monosaccharides available to E. coli. The monosaccharides repress expression of the E. coli tnaA gene encoding tryptophanase, thereby making more tryptophan available to Stickland fermenters in the gut environment. Blue arrows show events occurring in the absence of fibre, while green arrows designate events preferentially occurring in the presence of fibre. Thick and thin arrows depict enhanced and reduced flow of tryptophan, respectively. Although E. coli is shown here as a representative species of indole producers, we argue that the catabolite repression of the tnaA gene is widespread and applies to many other indole producers in the gut. Similarly, in a complex microbiota, fibre degradation and tryptophan utilization can also be performed by other bacterial species than B. thetaiotaomicron and C. sporogenes, as shown here, thus contributing to the diverse bacterial metabolite accumulation in the gut. Figure was created with BioRender.com.