Fig. 3.

Proposed strategy to identify tryptophan-catabolite-producing microbes and to investigate their role in human health and disease. Although a number of tryptophan-catabolite producing microbes have currently been identified (Table 1), no studies have until now taken their starting point from human data, meaning that we do not know the main bacterial producers of tryptophan catabolites in the human gut. Therefore, we suggest to start from human studies and combine metagenomics and metabolomics data in order to pinpoint the most relevant and potential tryptophan-catabolite producing microbes. Based on these associations, selected target species should be cultured in the laboratory and their in vitro production of tryptophan catabolites should be assessed by growth experiments and metabolic profiling. Combined with knowledge about their genomes, this will allow the identification of genes responsible for generation of tryptophan catabolites. Knocking out identified genes of interest will subsequently allow for confirmation of the function of the gene and for testing the importance of the particular gene in relevant animal models as recently exemplified²¹. Colonizing mice with a given mutant strain and the wild-type counterpart will furthermore allow the investigation of modes of action of the tryptophan catabolites on e.g., intestinal immune cells, intestinal barrier function, intestinal hormone secretion, the inherent gut microbiota, as well as on the immune cells in systemic circulation. Together, this will provide new insights about the role of tryptophan catabolites, and lead to a better understanding of the gut microbiota in human health and disease