Chronic kidney disease alters intestinal microbial flora
TL;DR: Uremia profoundly alters the composition of the gut microbiome and the biological impact of this phenomenon is unknown and awaits further investigation.
About: This article is published in Kidney International.The article was published on 2013-02-01 and is currently open access. It has received 826 citations till now. The article focuses on the topics: Microbiome & Prevotellaceae.
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TL;DR: The complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases is highlighted to highlight the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.
Abstract: Significant interest in recent years has focused on gut microbiota–host interaction because accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies such as atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. In addition to alterations in gut microbiota composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent studies revealed that gut microbiota can elicit a variety of effects on the host. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites, that can impact host physiology. Microbiota interact with the host through many pathways, including the trimethylamine/trimethylamine N -oxide pathway, short-chain fatty acids pathway, and primary and secondary bile acids pathways. In addition to these metabolism-dependent pathways, metabolism-independent processes are suggested to also potentially contribute to cardiovascular disease pathogenesis. For example, heart failure–associated splanchnic circulation congestion, bowel wall edema, and impaired intestinal barrier function are thought to result in bacterial translocation, the presence of bacterial products in the systemic circulation and heightened inflammatory state. These are thought to also contribute to further progression of heart failure and atherosclerosis. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites, and the development and progression of cardiovascular diseases. We will also discuss the roles of gut microbiota in normal physiology and the potential of modulating intestinal microbial inhabitants as novel therapeutic targets.
968 citations
Cites background from "Chronic kidney disease alters intes..."
...Ammonia and ammonium hydroxide disrupt the intestinal epithelial tight junctions.(131) This is thought to be a major cause of intestinal epithelial barrier dysfunction in CKD that allows the translocation of gut bacterial DNA and uremic toxins into systemic circulation, resulting in systemic inflammation....
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...It is well known that the composition of gut microbiota is markedly altered in patients with CKD, leading to an influx of circulating urea and other uremic toxins into the gut lumen.(131,132) Within the intestinal tract, urea is hydrolyzed by microbial urease to form large quantities of ammonia, which is then converted to ammonium hydroxide....
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TL;DR: Plasma TMAO levels are both elevated in patients with CKD and portend poorer long-term survival and chronic dietary exposures that increase TmaO directly contributes to progressive renal fibrosis and dysfunction in animal models.
Abstract: Rationale: Trimethylamine- N -oxide (TMAO), a gut microbial-dependent metabolite of dietary choline, phosphatidylcholine (lecithin), and l-carnitine, is elevated in chronic kidney diseases (CKD) and associated with coronary artery disease pathogenesis. Objective: To both investigate the clinical prognostic value of TMAO in subjects with versus without CKD, and test the hypothesis that TMAO plays a direct contributory role in the development and progression of renal dysfunction. Methods and Results: We first examined the relationship between fasting plasma TMAO and all-cause mortality over 5-year follow-up in 521 stable subjects with CKD (estimated glomerular filtration rate, 2 ). Median TMAO level among CKD subjects was 7.9 μmol/L (interquartile range, 5.2–12.4 μmol/L), which was markedly higher ( P P P P =0.036). Among non-CKD subjects, elevated TMAO levels portend poorer prognosis within cohorts of high and low cystatin C. In animal models, elevated dietary choline or TMAO directly led to progressive renal tubulointerstitial fibrosis and dysfunction. Conclusions: Plasma TMAO levels are both elevated in patients with CKD and portend poorer long-term survival. Chronic dietary exposures that increase TMAO directly contributes to progressive renal fibrosis and dysfunction in animal models.
811 citations
Cites background from "Chronic kidney disease alters intes..."
...Furthermore, perturbations of the composition of the gut microbial community in both human and experimental CKD are associated with significant elevations of gut-derived uremic toxins.(2) Such alterations have also been associated with increased systemic inflammatory burden, and thus are suspected to play a role in the pathogenesis of cardiovascular and renal disease progression in subjects with CKD....
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TL;DR: Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment.
Abstract: Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
629 citations
15 Apr 2020
TL;DR: Changes in Lachnospiraceae abundances according to health and disease are discussed and how nutrients from the host diet can influence their growth and how their metabolites can, in turn, influence host physiology are analyzed.
Abstract: The complex polymicrobial composition of human gut microbiota plays a key role in health and disease. Lachnospiraceae belong to the core of gut microbiota, colonizing the intestinal lumen from birth and increasing, in terms of species richness and their relative abundances during the host’s life. Although, members of Lachnospiraceae are among the main producers of short-chain fatty acids, different taxa of Lachnospiraceae are also associated with different intra- and extraintestinal diseases. Their impact on the host physiology is often inconsistent across different studies. Here, we discuss changes in Lachnospiraceae abundances according to health and disease. With the aim of harnessing Lachnospiraceae to promote human health, we also analyze how nutrients from the host diet can influence their growth and how their metabolites can, in turn, influence host physiology.
584 citations
TL;DR: Given the role of impaired Nrf2 activity in CKD-induced oxidative stress and inflammation, interventions aimed at restoring Nrf1 may be effective in retarding CKD progression and the potential utility of targeting NRF2 in the treatment of CKD is provided.
548 citations
References
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TL;DR: Copyright (©) 1999–2012 R Foundation for Statistical Computing; permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and permission notice are preserved on all copies.
Abstract: Copyright (©) 1999–2012 R Foundation for Statistical Computing. Permission is granted to make and distribute verbatim copies of this manual provided the copyright notice and this permission notice are preserved on all copies. Permission is granted to copy and distribute modified versions of this manual under the conditions for verbatim copying, provided that the entire resulting derived work is distributed under the terms of a permission notice identical to this one. Permission is granted to copy and distribute translations of this manual into another language, under the above conditions for modified versions, except that this permission notice may be stated in a translation approved by the R Core Team.
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TL;DR: Which elements of this often-quoted strategy for graphical representation of multivariate (multi-species) abundance data have proved most useful in practical assessment of community change resulting from pollution impact are identified.
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12,446 citations
TL;DR: A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms, and significant intersubject variability and differences between stool and mucosa community composition were discovered.
Abstract: The human endogenous intestinal microflora is an essential “organ” in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.
7,049 citations