Alteration of fecal tryptophan metabolism correlates with shifted microbiota and may be involved in pathogenesis of colorectal cancerOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study asked how gut tryptophan metabolism shifts in colorectal cancer and how it links to the microbiome. Researchers measured fecal tryptophan and its metabolites, tissue barrier and enzyme markers, and stool bacteria. Fecal tryptophan, kynurenine, and indoles were quantified by liquid chromatography-tandem mass spectrometry. Colon tissue IDO1 and ZO-1 were measured by RT-PCR, ZO-1 protein by immunohistochemistry, and gut bacteria by 16S ribosomal RNA gene sequencing. Correlations were then tested between fecal metabolites, barrier function, tissue enzymes, and bacterial genera.
Who was studied?
The cohort was 117 adults from China-Japan Friendship Hospital in Beijing, China, enrolled from March to December 2019. It included 46 patients with sporadic colorectal cancer, 33 with colorectal adenoma, and 38 healthy controls matched for age, sex, and body mass index. Cancer patients were newly diagnosed and untreated. Fecal samples and colon tissue were collected before resection. Metabolite analysis used 91 qualified stool samples.
What were the most important findings?
Fecal kynurenine was higher in cancer patients (1.51 nmol/g) than controls (0.81 nmol/g, p = 0.036), and the kynurenine-to-tryptophan ratio rose (p < 0.005). The indoles-to-tryptophan ratio fell in both adenoma and cancer patients (p = 0.003 and p = 0.029). Tissue IDO1 mRNA increased while ZO-1 mRNA and protein dropped sharply (p < 0.001). Indole-producing genera in Actinobacteria, Bacteroidetes, and Firmicutes declined in cancer and correlated positively with fecal indoles. The kynurenine-to-tryptophan ratio tracked tissue IDO1.
What are the greatest implications of this study?
The results suggest colorectal cancer features a weakened tryptophan indole pathway alongside a more active kynurenine pathway in colon tissue. Lower indole levels tracked with reduced gut barrier protein ZO-1, hinting that fewer indole-producing bacteria may loosen the barrier and redirect tryptophan toward kynurenine. This was observational, so causation is not established. The authors propose restoring tryptophan and microbiome balance as a possible preventive or therapeutic avenue worth further testing.