Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women

European Heart Journal, Journal Year: 2018, Volume and Issue: 40(7), P. 583 - 594

Published: Nov. 19, 2018

Carnitine and choline are major nutrient precursors for gut microbiota-dependent generation of the atherogenic metabolite, trimethylamine N-oxide (TMAO). We performed randomized-controlled dietary intervention studies to explore impact chronic patterns on TMAO levels, metabolism renal excretion.

Language: Английский

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Metabolomics toward personalized medicine

Mass Spectrometry Reviews, Journal Year: 2017, Volume and Issue: 38(3), P. 221 - 238

Published: Oct. 26, 2017

Metabolomics, which is the metabolites profiling in biological matrices, a key tool for biomarker discovery and personalized medicine has great potential to elucidate ultimate product of genomic processes. Over last decade, metabolomics studies have identified several relevant biomarkers involved complex clinical phenotypes using diverse systems. Most diseases result signature metabolic profiles that reflect sums external internal cellular activities. Metabolomics major role practice as it represents >95% workload laboratories worldwide. Many these require different analytical platforms, such Nuclear Magnetic Resonance (NMR), Mass Spectrometry (MS), Ultra Performance Liquid Chromatography (UPLC), while many clinically are still not routinely amenable detection currently available assays. Combining with genomics, transcriptomics, proteomics will significantly improved understanding disease mechanisms pathophysiology target phenotype. This comprehensive approach represent step forward toward providing precision medical care, individual accounted variability genes, environment, personal lifestyle. In this review, we compare evaluate strategies focus on “personalized” diagnostic, prognostic, therapeutic value, validated monitoring progression responses various management regimens.

Language: Английский

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Metabolomics for clinical use and research in chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2017, Volume and Issue: 13(5), P. 269 - 284

Published: March 6, 2017

Language: Английский

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Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: April 1, 2019

Abstract Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants including patients with stage 1–5 CKD healthy controls, we identify five metabolites, 5-methoxytryptophan (5-MTP), whose levels strongly correlate clinical markers 5-MTP decrease CKD, mouse kidneys after unilateral ureteral obstruction (UUO). Treatment ameliorates interstitial fibrosis, inhibits IκB/NF-κB signaling, enhances Keap1/Nrf2 signaling mice UUO or ischemia/reperfusion injury, as well cultured human cells. Overexpression tryptophan hydroxylase-1 (TPH-1), an enzyme involved synthesis, reduces injury by attenuating inflammation whereas TPH-1 deficiency exacerbates fibrosis activating NF-κB inhibiting Nrf2 pathways. Together, our results suggest that may serve a target the treatment CKD.

Language: Английский

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Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: March 2, 2020

Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large differences. We systematically investigated group-specific alterations by conducting stratified association analyses of 139 serum metabolites 1,517 individuals from the Neuroimaging Initiative with biomarkers. observed substantial differences effects 15 partially overlapping status groups. Several were not unstratified using as covariates. Combined stratification revealed further subgroup-specific limited ε4+ females. The suggest females experience greater impairment mitochondrial energy production than males. Dissecting heterogeneity pathogenesis can therefore enable grading biomedical relevance specific pathways within subgroups, guiding way personalized medicine.

Language: Английский

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Proteomics and Metabolomics in Kidney Disease, including Insights into Etiology, Treatment, and Prevention

Clinical Journal of the American Society of Nephrology, Journal Year: 2019, Volume and Issue: 15(3), P. 404 - 411

Published: Oct. 21, 2019

In this review of the application proteomics and metabolomics to kidney disease research, we key concepts, highlight illustrative examples, outline future directions. The proteome metabolome reflect influence environmental exposures in addition genetic coding. Circulating levels proteins metabolites are dynamic modifiable, thus amenable therapeutic targeting. Design analytic considerations studies should be tailored investigator’s goals. For identification clinical biomarkers, adjustment for all potential confounding variables, particularly GFR, strict significance thresholds warranted. However, approach has obscure biologic signals can overly conservative given high degree intercorrelation within metabolome. Mass spectrometry, often coupled up-front chromatographic separation techniques, is a major workhorse both metabolomics. High-throughput antibody- aptamer-based proteomic platforms have emerged as additional, powerful approaches assay proteome. As breadth coverage these methodologies continues expand, machine learning tools pathway analyses help select molecules greatest interest categorize them distinct themes. Studies date already made substantial effect, example elucidating target antigens membranous nephropathy, identifying signature urinary peptides that adds prognostic information albumin CKD, implicating circulating inflammatory mediators diabetic demonstrating role microbiome uremic milieu, highlighting bioenergetics modifiable factor AKI. Additional required replicate expand on findings independent cohorts. Further, more work needed understand longitudinal trajectory protein metabolite markers, perform transomics merged datasets, incorporate tissue–based investigation.

Language: Английский

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An overview of renal metabolomics

Kidney International, Journal Year: 2016, Volume and Issue: 91(1), P. 61 - 69

Published: Oct. 1, 2016

Language: Английский

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Development and Application of Ultra-Performance Liquid Chromatography-TOF MS for Precision Large Scale Urinary Metabolic Phenotyping

Analytical Chemistry, Journal Year: 2016, Volume and Issue: 88(18), P. 9004 - 9013

Published: Aug. 1, 2016

To better understand the molecular mechanisms underpinning physiological variation in human populations, metabolic phenotyping approaches are increasingly being applied to studies involving hundreds and thousands of biofluid samples. Hyphenated ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) has become a fundamental tool for this purpose. However, seemingly inevitable need analyze large multiple analytical batches UPLC-MS analysis poses challenge data quality which been recognized field. Herein, we describe detail fit-for-purpose platform, method set, sample workflow, capable sustained on an industrial scale allowing batch-free operation studies. Using complementary reversed-phase chromatography (RPC) hydrophilic interaction (HILIC) together with high resolution orthogonal acceleration time-of-flight mass (oaTOF-MS), exceptional measurement precision is exemplified independent epidemiological sets approximately 650 1000 participant Evaluation reference targets repeated injections pooled control (QC) samples distributed throughout each experiment demonstrates mean retention time relative standard deviation (RSD) <0.3% across all assays both peak area RSD <15% raw data. more globally assess profiling data, untargeted feature extraction was performed followed by filtration according intensity response QC dilution. Analysis remaining features within measurements demonstrated median values <20% RPC <25% HILIC assays. These represent as no normalization or feature-specific correction applied. While acquired single continuous batch, instances minor time-dependent drift were observed, highlighting utility techniques despite reducing dependency them generating results demonstrate that platform methodology presented herein fit-for-use studies, challenging assertion such screening inherently limited batch effects. Details pipeline used generate mitigate provided.

Language: Английский

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Holo-Omics: Integrated Host-Microbiota Multi-omics for Basic and Applied Biological Research

iScience, Journal Year: 2020, Volume and Issue: 23(8), P. 101414 - 101414

Published: July 25, 2020

From ontogenesis to homeostasis, the phenotypes of complex organisms are shaped by bidirectional interactions between host and their associated microbiota. Current technology can reveal many such combining multi-omic data from both hosts microbes. However, exploring full extent these requires careful consideration study design for efficient generation optimal integration derived (meta)genomics, (meta)transcriptomics, (meta)proteomics, (meta)metabolomics. In this perspective, we introduce holo-omic approach that incorporates microbiota domains untangle interplay two. We revisit recent literature on biomolecular host-microbe discuss implementation current limitations approach. anticipate application contribute opening new research avenues discoveries in biomedicine, biotechnology, agricultural aquacultural sciences, nature conservation, as well basic ecological evolutionary research.

Language: Английский

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Circulating Modified Metabolites and a Risk of ESRD in Patients With Type 1 Diabetes and Chronic Kidney Disease

Diabetes Care, Journal Year: 2017, Volume and Issue: 40(3), P. 383 - 390

Published: Jan. 13, 2017

Patients with type 1 diabetes (T1D) impaired renal function are at increased risk for end-stage disease (ESRD). Although the rate of progression varies, determinants and mechanisms this variation unknown.We examined serum metabolomic profiles associated in decline participants T1D (the Joslin Kidney Study prospective cohort). One hundred fifty-eight patients proteinuria chronic kidney stage 3 were followed a median 11 years to determine estimated glomerular filtration slopes from serial measurements creatinine ascertain time onset ESRD. Baseline samples subjected global profiling.One ten amino acids purine pyrimidine metabolites detected least 80% participants. Serum levels seven modified (C-glycosyltryptophan, pseudouridine, O-sulfotyrosine, N-acetylthreonine, N-acetylserine, N6-carbamoylthreonyladenosine, N6-acetyllysine) ESRD (P < 0.001) independent relevant clinical covariates. The significant correlated one another indices tubular injury.This cohort study T1D, proteinuria, baseline demonstrated that circulating certain experience faster decline, leading Whether some these candidate factors or just prognostic biomarkers needs be determined.

Language: Английский

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