Impaired tryptophan metabolism has been observed in subjects with IBS.[38] However, we did not find consistent patterns of the gene for the tryptophanase enzyme (EC 4.1.99.1) responsible for indole production across five cohorts when controlling for covariates, despite its significant enrichment in the IBS microbiome in both PRJEB42304 and PRJNA812699 cohorts (p < 0.05, Table S4, Supporting Information). This evidence concerns the gene TDO2 and irritable bowel syndrome.