Urinary intermediates of tryptophan as indicators of the gut microbial metabolism

Pavlová, Tereza; Vidová, Veronika; Bienertová-Vašků, Julie; Janků, Petr; Almáši, Martina; Klánová, Jana; Spáčil, Zdeněk

doi:10.1016/j.aca.2017.08.022

Cited by 68 publications

(49 citation statements)

References 42 publications

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“…It is worth mentioning that another bacterial tryptophan metabolite N-acetyltryptophan (NAT) was found to be up-regulated in our CRC patients compared with the controls. Its upregulation was also reported in the case of compromised gut microbiota 66 , 67 . NAT can prevent protein molecules from oxidative degradation by scavenging oxygen 68 .…”

Section: Discussionmentioning

confidence: 69%

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Deng¹,

Yao²,

Chen³

et al. 2020

J. Cancer

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Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives: We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients. Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE. Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed. Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system. Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N 1 ,N 12 -diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000; sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000; sensitivity: 89.9%; specificity: 92.0%) in the testing set. In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion: The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.

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Section: Discussionmentioning

confidence: 69%

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Deng¹,

Yao²,

Chen³

et al. 2020

J. Cancer

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“…In serum, mean concentrations in healthy adults have previously reported for IAA (1.3 µM), IPA (1.0 µM), and ILA (0.15 µM) 30 , while a recent study reported a mean serum IPA concentration of 50 nM 31 . Additionally, the mean concentrations of microbial tryptophan catabolites in the urine of pregnant women were recently reported for IAA (61 µM), methyl-IAA (8 µM), tryptamine (9 µM), and methyl-IPA (0.5 µM) 32 . Despite differences in the reported concentrations, these studies suggest that in adults, indole is the most abundant microbial tryptophan catabolite, followed by IAA and IPA.…”

Section: Bacterial Tryptophan Catabolism In the Gutmentioning

confidence: 95%

Microbial tryptophan catabolites in health and disease

2018

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Accumulating evidence implicates metabolites produced by gut microbes as crucial mediators of diet-induced host-microbial cross-talk. Here, we review emerging data suggesting that microbial tryptophan catabolites resulting from proteolysis are influencing host health. These metabolites are suggested to activate the immune system through binding to the aryl hydrocarbon receptor (AHR), enhance the intestinal epithelial barrier, stimulate gastrointestinal motility, as well as secretion of gut hormones, exert anti-inflammatory, anti-oxidative or toxic effects in systemic circulation, and putatively modulate gut microbial composition. Tryptophan catabolites thus affect various physiological processes and may contribute to intestinal and systemic homeostasis in health and disease.

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“…Recent discoveries have underscored the modulation of host immune systems by changes in the microbiota that affect Trp metabolism [ 43 ]. Activation of toll-like receptors by microbial components has been identified as a key factor in initiating Kyn metabolism and gut microbial homeostasis, as reduced toll-like receptor stimulation in germ-free mice resulted in decreased Trp metabolism [ 53 , 67 ].…”

Section: Role Of the Ido1 Pathway In Cancersmentioning

confidence: 99%

Targeting the IDO1 pathway in cancer: from bench to bedside

et al. 2018

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Indoleamine 2, 3-dioxygenases (IDO1 and IDO2) and tryptophan 2, 3-dioxygenase (TDO) are tryptophan catabolic enzymes that catalyze the conversion of tryptophan into kynurenine. The depletion of tryptophan and the increase in kynurenine exert important immunosuppressive functions by activating T regulatory cells and myeloid-derived suppressor cells, suppressing the functions of effector T and natural killer cells, and promoting neovascularization of solid tumors. Targeting IDO1 represents a therapeutic opportunity in cancer immunotherapy beyond checkpoint blockade or adoptive transfer of chimeric antigen receptor T cells. In this review, we discuss the function of the IDO1 pathway in tumor progression and immune surveillance. We highlight recent preclinical and clinical progress in targeting the IDO1 pathway in cancer therapeutics, including peptide vaccines, expression inhibitors, enzymatic inhibitors, and effector inhibitors.

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Urinary intermediates of tryptophan as indicators of the gut microbial metabolism

Cited by 68 publications

References 42 publications

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

Microbial tryptophan catabolites in health and disease

Targeting the IDO1 pathway in cancer: from bench to bedside

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