The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2018, Volume and Issue: 14(7), P. 442 - 456

Published: May 14, 2018

Language: Английский

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Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents

Gut, Journal Year: 2020, Volume and Issue: 69(12), P. 2131 - 2142

Published: April 2, 2020

Objective Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced studies in animals. The aim the study is to characterise relationships between intestinal microbiome composition, toxins and human end-stage disease (ESRD). Design Characterisation microbiome, serum faecal metabolome phenotypes a cohort 223 patients ESRD 69 healthy controls. Multidimensional data integration reveal links these datasets use chronic kidney (CKD) rodent models test effects on toxin accumulation severity. Results A group species enriched correlates tightly patient clinical variables encode functions involved secondary bile acids synthesis; relative abundance or concentrations metabolites. Microbiota transplanted injured germ-free mice antibiotic-treated rats induce higher production aggravated fibrosis oxidative stress more than microbiota Two species, Eggerthella lenta Fusobacterium nucleatum , increase promote development CKD rat model. probiotic Bifidobacterium animalis decreases reduces levels severity rats. Conclusion Aberrant sculpts detrimental aggravating outcomes, suggesting that will be promising target for diminishing toxicity those patients. Trial registration number This was registered at ClinicalTrials.gov ( NCT03010696 ).

Language: Английский

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Microbiome–metabolome reveals the contribution of gut–kidney axis on kidney disease

Journal of Translational Medicine, Journal Year: 2019, Volume and Issue: 17(1)

Published: Jan. 3, 2019

Dysbiosis represents changes in composition and structure of the gut microbiome community (microbiome), which may dictate physiological phenotype (health or disease). Recent technological advances efforts metagenomic metabolomic analyses have led to a dramatical growth our understanding microbiome, but still, mechanisms underlying microbiome-host interactions healthy diseased state remain elusive their elucidation is infancy. Disruption normal microbiota lead intestinal dysbiosis, barrier dysfunction, bacterial translocation. Excessive uremic toxins are produced as result alteration, including indoxyl sulphate, p-cresyl trimethylamine-N-oxide, all implicated variant processes kidney diseases development. This review focuses on pathogenic association between (the gut-kidney axis), covering CKD, IgA nephropathy, nephrolithiasis, hypertension, acute injury, hemodialysis peritoneal dialysis clinic. Targeted interventions probiotic, prebiotic symbiotic measures discussed for potential re-establishing symbiosis, more effective strategies treatment patients suggested. The novel insights into dysbiosis helpful develop therapeutic preventing attenuating complications.

Language: Английский

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Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease

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

Published: April 23, 2019

Diabetic kidney disease is a major cause of renal failure that urgently necessitates breakthrough in management. Here we show using untargeted metabolomics levels phenyl sulfate, gut microbiota-derived metabolite, increase with the progression diabetes rats overexpressing human uremic toxin transporter SLCO4C1 kidney, and are decreased limited proteinuria. In experimental models diabetes, sulfate administration induces albuminuria podocyte damage. diabetic patient cohort, significantly correlate basal predicted 2-year patients microalbuminuria. Inhibition tyrosine phenol-lyase, bacterial enzyme responsible for synthesis phenol from dietary before it metabolized into liver, reduces mice. Together, our results suggest contributes to could be used as marker future therapeutic target disease.

Language: Английский

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Probiotics and chronic kidney disease

Kidney International, Journal Year: 2015, Volume and Issue: 88(5), P. 958 - 966

Published: Sept. 16, 2015

Language: Английский

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Circulating trimethylamine N‐oxide and the risk of cardiovascular diseases: a systematic review and meta‐analysis of 11 prospective cohort studies

Journal of Cellular and Molecular Medicine, Journal Year: 2017, Volume and Issue: 22(1), P. 185 - 194

Published: Aug. 7, 2017

Circulating trimethylamine N-oxide (TMAO), a canonical metabolite from gut flora, has been related to the risk of cardiovascular disorders. However, association between circulating TMAO and events not quantitatively evaluated. We performed systematic review meta-analysis all available cohort studies regarding baseline subsequent events. Embase PubMed databases were searched for relevant studies. The overall hazard ratios developing (CVEs) mortality extracted. Heterogeneity among included was evaluated with Cochran's Q Test I2 statistics. A random-effect model or fixed-effect applied depending on heterogeneity. Subgroup analysis meta-regression used evaluate source Among 11 eligible studies, three reported both CVE outcome, one only CVEs other seven provided data only. Higher associated 23% higher (HR = 1.23, 95% CI: 1.07-1.42, 31.4%) 55% all-cause 1.55, 1.19-2.02, 80.8%). Notably, latter may be blunted by potential publication bias, although sensitivity omitting study at time did significantly change results. Further subgroup support that location study, follow-up duration, year, population characteristics samples affect results significantly. independently predict mortality.

Language: Английский

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Gut–organ axis: a microbial outreach and networking

Letters in Applied Microbiology, Journal Year: 2020, Volume and Issue: 72(6), P. 636 - 668

Published: May 30, 2020

Human gut microbiota (GM) includes a complex and dynamic population of microorganisms that are crucial for well‐being survival the organism. It has been reported as diverse relatively stable with shared core microbiota, including Bacteroidetes Firmicutes major dominants. They key regulators body homeostasis, involving both intestinal extra‐intestinal effects by influencing many physiological functions such metabolism, maintenance barrier inflammation hematopoiesis. Any alteration in GM community structures not only trigger disorders but also influence other organs cause associated diseases. In recent past, defined 'vital organ' its involvement organs; thus, establishing link or bi‐ multidirectional communication axis between via neural, endocrine, immune, humoral metabolic pathways. Alterations have linked to several diseases known humans; although exact interaction mechanism is yet be defined. this review, bidirectional relationship vital human was envisaged discussed under headings. Furthermore, disease symptoms were revisited redefine network microbes organs. Significance Impact Study: Gut metabolites play role maintaining health various Literature review evidences suggest any composition diversity triggers influences cause‐associated we attempted provide readers broad overview connection Our effort will foster development personalized treatment can adopted evolved targeting microbiome deliberately controlled manner.

Language: Английский

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Chronic kidney disease and the gut microbiome

AJP Renal Physiology, Journal Year: 2019, Volume and Issue: 316(6), P. F1211 - F1217

Published: March 13, 2019

The gut microbiome is composed of a diverse population bacteria that have beneficial and adverse effects on human health. has recently gained attention increasingly noted to play significant role in health number disease states. Increasing urea concentration during chronic kidney (CKD) leads alterations the intestinal flora can increase production gut-derived toxins alter epithelial barrier. These changes lead an acceleration process injury. A strategies been proposed interrupt this pathway injury CKD. purpose review summarize CKD, tools used study microbial population, attempts its composition for therapeutic purposes.

Language: Английский

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The molecular mechanisms of hemodialysis vascular access failure

Kidney International, Journal Year: 2016, Volume and Issue: 89(2), P. 303 - 316

Published: Jan. 22, 2016

The arteriovenous fistula has been used for more than 50 years to provide vascular access patients undergoing hemodialysis. More 1.5 million worldwide have end stage renal disease and this population will continue grow. is the preferred patients, but its patency rate at 1 year only 60%. majority of fistulas fail because intimal hyperplasia. In recent years, there many studies investigating molecular mechanisms responsible hyperplasia subsequent thrombosis. These identified common pathways including inflammation, uremia, hypoxia, sheer stress, increased thrombogenicity. cellular lead proliferation, migration, eventually stenosis. work synergistically through shared messengers. review, we examine literature concerning basis hemodialysis malfunction.

Language: Английский

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Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

Clinical Science, Journal Year: 2018, Volume and Issue: 132(5), P. 509 - 522

Published: March 9, 2018

In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number beneficial bacteria that produce short-chain fatty acids, an essential nutrient for colonic epithelium, concurrent with increase uremic such as indoxyl sulphate, p-cresyl trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation degradation intercellular tight junctions, gut-derived translocate into bloodstream exert systemic effects. this review, we discuss evidence supporting role promoting multiorgan dysfunction via inflammatory, oxidative stress, apoptosis pathways. End-organ effects include vascular calcification, fibrosis, anemia, impaired immune system, adipocyte insulin resistance, low turnover bone disease. Higher blood levels are associated increased cardiovascular events mortality CKD population. Clinical trials have examined interventions trap toxic products or reverse microbial dysbiosis oral activated charcoal AST-120, prebiotics probiotics not shown impact on survival outcomes but were limited by sample size short trials. summary, microbiome major contributor adverse progression CKD.

Language: Английский

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