Abstract:
There is limited understanding of the role of host metabolism in the pathophysiology of human
tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic
pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the
spectrum of TB infection and disease. This regulation is characterized by increased catabolism of
tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB
infection (LTBI). Further, we found that tryptophan catabolism is reversed with effective treatment
of both active TB disease and LTBI in a manner commensurate with bacterial clearance. Persons
with active TB and LTBI also exhibited increased expression of indoleamine 2,3-dioxygenase-1
(IDO-1), suggesting IDO-1 mediates observed increases in tryptophan catabolism. Together, these
data indicate IDO-1–mediated tryptophan catabolism is highly preserved in the human response
to Mycobacterium tuberculosis and could be a target for biomarker development as well as hostdirected
therapies.
