Mass spectrometric measurement of urinary kynurenine-to-tryptophan ratio in children with and without urinary tract infection

Yarbrough, Melanie L.; Briden, Kelleigh E.; Mitsios, John V.; Weindel, Annette L.; Terrill, Cindy; Hunstad, David A.; Dietzen, Dennis J.

doi:10.1016/j.clinbiochem.2018.04.014

Cited by 10 publications

(6 citation statements)

References 31 publications

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“…Tryptophan, as well as products of the tryptophan catabolic pathway, are involved in modulating a variety of host functions, including the nervous and immune systems [ 85 – 94 ], and have been implicated in the gut-brain axis [ 71 , 95 ]. Tryptophan metabolites are also involved in UPEC pathogenesis [ 96 – 99 ] and have also been previously shown to be elevated in the urine of a pediatric cohort of symptomatic UTI patients [ 100 ], suggesting tryptophan metabolism may be important in the context of recurrent UTI. The OTU41-characteristic genes also included several genes predicted to function in the biosynthesis or transport of cobalamin, which has been suggested to be a key regulator of the gut microbiome [ 101 ] and critical in regulating host-microbial interactions [ 102 ].…”

Section: Discussionmentioning

confidence: 99%

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections

et al. 2021

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Background Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. Results The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor’s association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. Conclusion While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. Trial registration Clinical trial registration number: ClinicalTrials.govNCT01776021.

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Section: Discussionmentioning

confidence: 99%

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections

et al. 2021

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“…IDO can be studied quantitatively by measuring mRNA expression or protein levels or enzymatic activity (product-to-substrate ratio; Li et al, 2011; Mehra et al, 2012; Suzuki et al, 2012, 2013; Huang et al, 2013; Bipath et al, 2015; Zhang et al, 2019). IDO activity can be detected in host fluids including blood, sputum, pleural fluid, cerebrospinal fluid and urine (Almeida et al, 2009; Li et al, 2011; Suzuki et al, 2012, 2013; Bipath et al, 2015; Adu-Gyamfi et al, 2017; Gautam et al, 2018; Yarbrough et al, 2018). IDO mRNA expression has been studied using rt-PCR, and IDO protein has been measured by western blot, radioimmunoassay and immunofluorescence methods (Almeida et al, 2009; Soliman et al, 2013; Zhang et al, 2019).…”

Section: Laboratory Measurement Of Ido Activitymentioning

confidence: 99%

Indoleamine 2, 3-Dioxygenase-Mediated Tryptophan Catabolism: A Leading Star or Supporting Act in the Tuberculosis and HIV Pas-de-Deux?

Adu-Gyamfi

Savulescu²,

George

et al. 2019

Front. Cell. Infect. Microbiol.

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Progression from latency to active Tuberculosis (TB) disease is mediated by incompletely understood host immune factors. The definitive characteristic of progressive human immunodeficiency virus (HIV) disease is a severe loss in number and function of T lymphocytes. Among the many possible mediators of T lymphocyte loss and ineffective function is the activity of the immune-modulatory enzyme indoleamine 2,3-dioxygenase (IDO). IDO is the rate-limiting enzyme converting tryptophan to kynurenine. IDO activity was initially recognized to mediate tolerance at the foeto-maternal interface. Recently, IDO activity has also been noted to play a critical role in immune tolerance to pathogens. Studies of host immune and metabolic mediators have found IDO activity significantly elevated in HIV and TB disease. In this review, we explore the link between IDO-mediated tryptophan catabolism and the presence of active TB disease in HIV-infected patients. We draw attention to increased IDO activity as a key factor marking the progression from latent to active TB disease in HIV-infected patients.

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“…Notwithstanding our positive findings, further clinical trials with larger clinical sample size are required to validate the applicability of urinary KYN–TRP ratio for the surveillance of bladder cancer recurrence. For instance, the TRP–KYN metabolic axis may be dynamically modulated by other factors, including dietary supply of nutrients [28], metabolic syndrome [29], and inflammation [30]. Follow‐up studies are warranted to evaluate the trajectory of the KYN–TRP ratio on clinical intervention (e.g.…”

Section: Discussionmentioning

confidence: 99%

Tryptophan–kynurenine ratio as a biomarker of bladder cancer

et al. 2020

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Objectives To investigate plasma and urinary kynurenine (KYN)–tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3‐dioxygenase 1 (IDO1) in relation to tryptophan 2,3‐dioxygenase (TDO2) in bladder tumour, and the correlation of KYN–TRP ratio with bladder tumour burden. Methods Metabotyping of the TRP–KYN metabolic axis was performed via a clinical case–control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues. Correlational experiments between KYN–TRP ratio and bladder tumour were performed using a murine orthotopic prostate‐specific antigen (PSA)‐secreting MB49 bladder cancer model. Results We established for the first time that plasma TRP level was significantly decreased, while both plasma and urinary KYN–TRP ratios were significantly higher in bladder cancer patients, and expression level of IDO1 but not TDO2 was increased in human bladder tumour. We reported the positive correlation between IDO1 expression, KYN–TRP ratio, normalized PSA to creatinine, and bladder tumour burden in the murine model. Conclusion Kynurenine–tryptophan ratio is a promising surveillance biomarker for bladder cancer, but would require further validation before clinical translation.

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Mass spectrometric measurement of urinary kynurenine-to-tryptophan ratio in children with and without urinary tract infection

Abstract: Measurement of Trp and Kyn by LC-MS/MS is accurate and precise in serum and urine specimens. While urinary K/T ratio is not a specific biomarker for UTI, it may represent a general indicator of a systemic inflammatory process.

Cited by 10 publications

References 31 publications

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections

Indoleamine 2, 3-Dioxygenase-Mediated Tryptophan Catabolism: A Leading Star or Supporting Act in the Tuberculosis and HIV Pas-de-Deux?

Tryptophan–kynurenine ratio as a biomarker of bladder cancer

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