Toxins

Editorial

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3 pages, 201 KiB

Open AccessEditorial

Gut Microbiota Dynamics and Uremic Toxins

by Eikan Mishima and Takaaki Abe

Toxins 2022, 14(2), 146; https://doi.org/10.3390/toxins14020146 - 17 Feb 2022

Cited by 2 | Viewed by 2263

Abstract

Recent evidence has highlighted the importance of the gut microbiota in the pathophysiology of kidney diseases [...] Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

Research

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10 pages, 306 KiB

Open AccessArticle

Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease

by Amina El Amouri, Evelien Snauwaert, Aurélie Foulon, Charlotte Vande Moortel, Maria Van Dyck, Koen Van Hoeck, Nathalie Godefroid, Griet Glorieux, Wim Van Biesen, Johan Vande Walle, Ann Raes and Sunny Eloot

Toxins 2021, 13(3), 225; https://doi.org/10.3390/toxins13030225 - 19 Mar 2021

Cited by 21 | Viewed by 3130

Abstract

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim [...] Read more.

Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (−3.1% (−5.9%; −0.3%) (p = 0.035)), free p-cresyl sulfate (−2.5% (−4.7%; −0.3%) (p = 0.034)), total indole acetic acid (IAA) (−1.6% (−3.0%; −0.3%) (p = 0.020)), free IAA (−6.6% (−9.3%; −3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (−3.0% (−5.6%; −0.5%) (p = 0.021)) and free pCG levels (−3.3% (−5.8%; −0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

12 pages, 1171 KiB

Open AccessArticle

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD

by Christophe Barba, Christophe O. Soulage, Gianvito Caggiano, Griet Glorieux, Denis Fouque and Laetitia Koppe

Toxins 2020, 12(12), 741; https://doi.org/10.3390/toxins12120741 - 24 Nov 2020

Cited by 44 | Viewed by 4586

Abstract

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source [...] Read more.

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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13 pages, 4274 KiB

Open AccessArticle

Germ-Free Conditions Modulate Host Purine Metabolism, Exacerbating Adenine-Induced Kidney Damage

by Eikan Mishima, Mariko Ichijo, Takeshi Kawabe, Koichi Kikuchi, Yukako Akiyama, Takafumi Toyohara, Takehiro Suzuki, Chitose Suzuki, Atsuko Asao, Naoto Ishii, Shinji Fukuda and Takaaki Abe

Toxins 2020, 12(9), 547; https://doi.org/10.3390/toxins12090547 - 26 Aug 2020

Cited by 28 | Viewed by 5396

Abstract

Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of [...] Read more.

Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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Review

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9 pages, 563 KiB

Open AccessReview

Significance of the Gut Microbiota in Acute Kidney Injury

by Taku Kobayashi, Yasunori Iwata, Yusuke Nakade and Takashi Wada

Toxins 2021, 13(6), 369; https://doi.org/10.3390/toxins13060369 - 22 May 2021

Cited by 21 | Viewed by 4603

Abstract

Recent studies have revealed that the gut microbiota plays a crucial role in maintaining a healthy, as well as diseased condition. Various organs and systems, including the kidney, are affected by the gut microbiota. While the impacts of the gut microbiota have been [...] Read more.

Recent studies have revealed that the gut microbiota plays a crucial role in maintaining a healthy, as well as diseased condition. Various organs and systems, including the kidney, are affected by the gut microbiota. While the impacts of the gut microbiota have been reported mainly on chronic kidney disease, acute kidney injury (AKI) is also affected by the intestinal environment. In this review, we discussed the pathogenesis of AKI, highlighting the relation to the gut microbiota. Since there is no established treatment for AKI, new treatments for AKI are highly desired. Some kinds of gut bacteria and their metabolites reportedly have protective effects against AKI. Current studies provide new insights into the role of the gut microbiota in the pathogenesis of AKI. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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16 pages, 3695 KiB

Open AccessEditor’s ChoiceReview

by Kensei Taguchi, Kei Fukami, Bertha C. Elias and Craig R. Brooks

Toxins 2021, 13(5), 361; https://doi.org/10.3390/toxins13050361 - 19 May 2021

Cited by 20 | Viewed by 5392

Abstract

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually [...] Read more.

Chronic kidney disease (CKD) is a public health concern that affects approximately 10% of the global population. CKD is associated with poor outcomes due to high frequencies of comorbidities such as heart failure and cardiovascular disease. Uremic toxins are compounds that are usually filtered and excreted by the kidneys. With the decline of renal function, uremic toxins are accumulated in the systemic circulation and tissues, which hastens the progression of CKD and concomitant comorbidities. Gut microbial dysbiosis, defined as an imbalance of the gut microbial community, is one of the comorbidities of CKD. Meanwhile, gut dysbiosis plays a pathological role in accelerating CKD progression through the production of further uremic toxins in the gastrointestinal tracts. Therefore, the gut-kidney axis has been attracting attention in recent years as a potential therapeutic target for stopping CKD. Trimethylamine N-oxide (TMAO) generated by gut microbiota is linked to the progression of cardiovascular disease and CKD. Also, advanced glycation endproducts (AGEs) not only promote CKD but also cause gut dysbiosis with disruption of the intestinal barrier. This review summarizes the underlying mechanism for how gut microbial dysbiosis promotes kidney injury and highlights the wide-ranging interventions to counter dysbiosis for CKD patients from the view of uremic toxins such as TMAO and AGEs. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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9 pages, 8761 KiB

Open AccessEditor’s ChoiceReview

Two Gut Microbiota-Derived Toxins Are Closely Associated with Cardiovascular Diseases: A Review

by Tomoya Yamashita, Naofumi Yoshida, Takuo Emoto, Yoshihiro Saito and Ken-ichi Hirata

Toxins 2021, 13(5), 297; https://doi.org/10.3390/toxins13050297 - 22 Apr 2021

Cited by 17 | Viewed by 3529

Abstract

Cardiovascular diseases (CVDs) have become a major health problem because of the associated high morbidity and mortality rates observed in affected patients. Gut microbiota has recently been implicated as a novel endocrine organ that plays critical roles in the regulation of cardiometabolic and [...] Read more.

Cardiovascular diseases (CVDs) have become a major health problem because of the associated high morbidity and mortality rates observed in affected patients. Gut microbiota has recently been implicated as a novel endocrine organ that plays critical roles in the regulation of cardiometabolic and renal functions of the host via the production of bioactive metabolites. This review investigated the evidence from several clinical and experimental studies that indicated an association between the gut microbiota-derived toxins and CVDs. We mainly focused on the pro-inflammatory gut microbiota-derived toxins, namely lipopolysaccharides, derived from Gram-negative bacteria, and trimethylamine N-oxide and described the present status of research in association with these toxins, including our previous research findings. Several clinical studies aimed at exploring the effectiveness of reducing the levels of these toxins to inhibit cardiovascular events are currently under investigation or in the planning stages. We believe that some of the methods discussed in this review to eliminate or reduce the levels of such toxins in the body could be clinically applied to prevent CVDs in the near future. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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23 pages, 964 KiB

Open AccessEditor’s ChoiceReview

The Impact of CKD on Uremic Toxins and Gut Microbiota

by Jacek Rysz, Beata Franczyk, Janusz Ławiński, Robert Olszewski, Aleksanda Ciałkowska-Rysz and Anna Gluba-Brzózka

Toxins 2021, 13(4), 252; https://doi.org/10.3390/toxins13040252 - 31 Mar 2021

Cited by 143 | Viewed by 15166

Abstract

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of [...] Read more.

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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20 pages, 1447 KiB

Open AccessReview

Gut-Derived Protein-Bound Uremic Toxins

by Amanda L. Graboski and Matthew R. Redinbo

Toxins 2020, 12(9), 590; https://doi.org/10.3390/toxins12090590 - 11 Sep 2020

Cited by 80 | Viewed by 8933

Abstract

Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from [...] Read more.

Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from cardiovascular disease and other causes. Several of the most harmful uremic toxins are produced by the gut microbiota. Furthermore, many such toxins are protein-bound and are therefore recalcitrant to removal by dialysis. We review the derivation and pathological mechanisms of gut-derived, protein-bound uremic toxins (PBUTs). We further outline the emerging relationship between kidney disease and gut dysbiosis, including the bacterial taxa altered, the regulation of microbial uremic toxin-producing genes, and their downstream physiological and neurological consequences. Finally, we discuss gut-targeted therapeutic strategies employed to reduce PBUTs. We conclude that targeting the gut microbiota is a promising approach for the treatment of CKD by blocking the serum accumulation of PBUTs that cannot be eliminated by dialysis. Full article

(This article belongs to the Special Issue Gut Microbiota Dynamics and Uremic Toxins)

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