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

  title={Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins.},
  author={Wei Ling Lau and Javad Savoj and Michael B Nakata and Nosratola D. Vaziri},
  journal={Clinical science},
  volume={132 5},
In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived… 

Microbiome in Chronic Kidney Disease

The purpose of this review is to summarize the changes of gut microbiome and the protein bound uremic toxins which are observed in CKD and in different kidney replacement strategies, and to review the connection between microbiome, clinical implications and immune response in CKd.

The consequences of altered microbiota in immune-related chronic kidney disease.

  • W. LauYongen ChangN. Vaziri
  • Biology, Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2020
Animal and clinical studies suggest potential benefits of dietary and probiotic interventions in slowing the progression of immune-related kidney diseases.

Chronic kidney disease, uremic milieu, and its effects on gut bacterial microbiota dysbiosis.

16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57BL/6J mice that underwent a remnant kidney model are presented and it is established that changes in microbiota take place in the early gastrointestinal tract.

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

The novel insights into the dysbiosis of the gut microbiota in kidney diseases are helpful to develop novel therapeutic strategies for preventing or attenuating kidney diseases and complications.

Intestinal microbiota alterations in chronic kidney disease and the influence of dietary components

A review of the link between nutrients, microbiota and uremic toxins with chronic kidney disease progression has been studied thoroughly and potential mechanisms of action and efficacy of probiotics, prebiotics and low protein diets are outlined.

Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells

Recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfates, the two best characterized protein-bound uremic retention solutes are summarized.

Short-Chain Fatty Acids Alleviate Hepatocyte Apoptosis Induced by Gut-Derived Protein-Bound Uremic Toxins

Flow cytometry analysis indicated that three uremic toxins induced varying degrees of apoptosis in hepatocytes and HA represented the highest efficacy, and coculture with SCFAs for 24 h significantly improved HA-induced apoptoses in THLE-2 cells, and propionate represented thehighest efficacy.

Impact of Gut Dysbiosis on Neurohormonal Pathways in Chronic Kidney Disease

The impact of an altered gut microbiota on neuroendocrine pathways such as the hypothalamus–pituitary–adrenal axis, the production of neurotransmitters and neuroactive compounds, tryptophan metabolism, and the cholinergic anti-inflammatory pathway are discussed.

Dietary Components That May Influence the Disturbed Gut Microbiota in Chronic Kidney Disease

Gut microbiota imbalance is common in patients with chronic kidney disease (CKD) and associates with factors such as increased circulating levels of gut-derived uremic toxins, inflammation, and

The Therapeutic Strategies for Uremic Toxins Control in Chronic Kidney Disease

This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease and the research status of Chinese herbal medicine is discussed.



Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

It is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection.

The Gut as a Source of Inflammation in Chronic Kidney Disease

The evidence points to a strong relationship between intestinal inflammation and adverse outcomes in CKD, and more trials investigating gut-targeted therapeutics are needed.

The gut microbiome, kidney disease, and targeted interventions.

  • A. RamezaniD. Raj
  • Biology, Medicine
    Journal of the American Society of Nephrology : JASN
  • 2014
The quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship are reviewed, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis.

The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease.

It is discussed how the metabolic alterations of uremia favor pathogen overgrowth (dysbiosis) in the gut and an increased translocation of living bacteria and bacterial components has the potential to activate innate immunity and systemic inflammation.

Uremic toxins originating from colonic microbial metabolism.

There is evidence that besides reduced renal clearance, increased colonic generation and absorption explain the high levels of bacterial URMs in CKD.

Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment.

  • N. VaziriYing-yong ZhaoM. Pahl
  • Biology
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2016
Together, uremia-induced impairment of the intestinal epithelial barrier structure and function and changes in composition of the gut microbiome contribute to the systemic inflammation and uremic toxicity by accommodating the translocation of endotoxin, microbial fragments and other noxious luminal products in the circulation.

Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease

Uremia-induced disruption of intestinal TJ and barrier function is, in part, mediated by urea which is generally considered to be a nontoxic retained metabolite, revealing a novel mechanism for a salutary effect of urea-lowering strategies, e.g. low-protein diet and longer and more frequent dialysis regimens in advanced CKD.

Uremic Plasma Impairs Barrier Function and Depletes the Tight Junction Protein Constituents of Intestinal Epithelium

Findings point to the presence of as-yet unidentified product(s) in the uremic plasma capable of depleting epithelial TJ and impairs its barrier function, events which are mediated by agents which are partially removed by hemodialysis.

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

The expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls was studied, and the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent NRF2 activator was demonstrated.

High Amylose Resistant Starch Diet Ameliorates Oxidative Stress, Inflammation, and Progression of Chronic Kidney Disease

High resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats and future studies are needed to explore the impact of HAM-RS2 in CKD patients.