The hematologic and pathologic effects of orally administered L-tryptophan and indoleactic acid and of L-tryptophan administered IV were studied in ponies. Sixteen adult Shetland ponies were allotted into 4 experimental groups. Group 1 consisted of 5 ponies (1-5) given 0.6 g of tryptophan/kg of body weight in a water slurry via stomach tube. Group 2 included 4 ponies (6-9) given 0.35 g of tryptophan/kg orally. Group-3 ponies (10-13) were given 0.35 g of indoleacetic acid/kg orally. Group 4 consisted of 3 ponies (14-16) given a single 4-hour IV infusion of 0.1 g of tryptophan/kg. Restlessness, increased respiratory rate, hemolysis, and hemoglobinuria were detected in 4 of the 5 group-1 ponies. Only pony 7 in group 2 developed hemolysis, hemoglobinuria, and a significant increase in respiratory rate. Renal pathologic lesions, consistent with hemoglobinuric nephrosis, were seen in ponies 2, 4, 5, and 7. Bronchiolar degeneration was evident in 4 of 9 ponies given tryptophan orally. The importance of these respiratory lesions was unknown. Clinical or pathologic abnormalities were not noticed in the ponies of groups 3 and 4. Mean plasma tryptophan values increased significantly in groups 1 and 2 at 6 hours after dosing. A second peak of tryptophan was detected in both groups at 12 hours. Values returned to predose values by 48 hours. Plasma indole and 3-methylindole concentrations were detectable in only 2 ponies (4 and 7). In vitro incubations of cecal fluid from ponies 6, 8, and 9 yielded a percentage conversion of tryptophan to indole of 16.75%, 5.84%, and 7.96%, respectively. 3-Methylindole was not produced. These results suggested that indole was the major metabolite of orally administered tryptophan in these ponies.

The gut microbiota has a major contribution in human physiology and influences disease pathogenesis, including in tuberculosis (TB) lung infection. Gut-lung axis has demonstrated the interplay of these two organs, mediated by metabolites produced by the gut microbes or derived from host molecules transformation. Tryptophan (Trp) is one of the essential aromatic amino acids catabolized as kynurenine, serotonin (5-hydroxytryptamine), and indole derivatives, including indole propionic acid (IPA), via 3 pathways. The latter was microbiota-derived Trp catabolism, which has known to have an immunomodulatory role, as ligands for Aryl hydrocarbon Receptor (AhR). Intriguingly, Mycobacterium tuberculosis required Trp as a nitrogen source, especially in CD4+ T cells-generated stress, to survive in the phagosome of macrophage and to cause disease. Recently, IPA is identified as a new anti-mycobacterial compound, which is specific and has broad spectrum of anti-mycobacterial activity. The structural similarity of this gut microbiota-derived metabolite and Trp allows IPA to inhibit the TrpE anthranilate synthase in Trp biosynthesis pathway in Mtb. In this review, we summarize findings from recent work by focusing on the role of Trp metabolites in host cells in TB infection.  A better understanding of this chemical signal could potentially serve as a novel strategy for managing this chronic inflammatory disease.