The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease

Overview

Journal Front Pharmacol

Date 2022 Apr 4

PMID 35370631

Authors

Yinghui Huang

Wang Xin

Jiachuan Xiong

Mengying Yao

Bo Zhang

Jinghong Zhao

Affiliations

Soon will be listed here.

Abstract

Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.

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References

Cani P, Neyrinck A, Fava F, Knauf C, Burcelin R, Tuohy K . Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007; 50(11):2374-83. DOI: 10.1007/s00125-007-0791-0. View

Ren Z, Fan Y, Li A, Shen Q, Wu J, Ren L . Alterations of the Human Gut Microbiome in Chronic Kidney Disease. Adv Sci (Weinh). 2020; 7(20):2001936. PMC: 7578882. DOI: 10.1002/advs.202001936. View

Ranganathan N, Ranganathan P, Friedman E, Joseph A, Delano B, Goldfarb D . Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv Ther. 2010; 27(9):634-47. DOI: 10.1007/s12325-010-0059-9. View

Chen Y, Wu M, Hu P, Chen T, Shen W, Chang W . Effects and Safety of an Oral Adsorbent on Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis. J Clin Med. 2019; 8(10). PMC: 6832608. DOI: 10.3390/jcm8101718. View

Liu L, Liu Y, Zhang Y, Bi X, Nie L, Liu C . High phosphate-induced downregulation of PPARγ contributes to CKD-associated vascular calcification. J Mol Cell Cardiol. 2017; 114:264-275. DOI: 10.1016/j.yjmcc.2017.11.021. View

Mamic P, Chaikijurajai T, Tang W . Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review. J Mol Cell Cardiol. 2020; 152:105-117. PMC: 7981261. DOI: 10.1016/j.yjmcc.2020.12.001. View

Lekawanvijit S, Kompa A, Wang B, Kelly D, Krum H . Cardiorenal syndrome: the emerging role of protein-bound uremic toxins. Circ Res. 2012; 111(11):1470-83. DOI: 10.1161/CIRCRESAHA.112.278457. View

Huang Y, Zhou J, Wang S, Xiong J, Chen Y, Liu Y . Indoxyl sulfate induces intestinal barrier injury through IRF1-DRP1 axis-mediated mitophagy impairment. Theranostics. 2020; 10(16):7384-7400. PMC: 7330852. DOI: 10.7150/thno.45455. View

Yang K, Wang C, Nie L, Zhao X, Gu J, Guan X . Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy. J Am Soc Nephrol. 2015; 26(10):2434-46. PMC: 4587686. DOI: 10.1681/ASN.2014060543. View

10.

Liu M, Tang F, Liu Q, Xiao J, Cao H, Chen X . Inhibition of resveratrol glucosides (REs) on advanced glycation endproducts (AGEs) formation: inhibitory mechanism and structure-activity relationship. Nat Prod Res. 2018; 34(17):2490-2494. DOI: 10.1080/14786419.2018.1538224. View

11.

Cammarota G, Ianiro G, Tilg H, Rajilic-Stojanovic M, Kump P, Satokari R . European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017; 66(4):569-580. PMC: 5529972. DOI: 10.1136/gutjnl-2016-313017. View

12.

Rui-Zhi T, Hui D, Jian-Chun L, Xia Z, Xiao-Jia W, Dan W . Bunge and Panax Notoginseng Formula (A&P) Combined With Bifidobacterium Contribute a Renoprotective Effect in Chronic Kidney Disease Through Inhibiting Macrophage Inflammatory Response in Kidney and Intestine. Front Physiol. 2020; 11:583668. PMC: 7729014. DOI: 10.3389/fphys.2020.583668. View

13.

Yang K, Du C, Wang X, Li F, Xu Y, Wang S . Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice. Blood. 2017; 129(19):2667-2679. DOI: 10.1182/blood-2016-10-744060. View

14.

Vaziri N, Liu S, Lau W, Khazaeli M, Nazertehrani S, Farzaneh S . High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS One. 2014; 9(12):e114881. PMC: 4260945. DOI: 10.1371/journal.pone.0114881. View

15.

Bruci A, Tuccinardi D, Tozzi R, Balena A, Santucci S, Frontani R . Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure. Nutrients. 2020; 12(2). PMC: 7071259. DOI: 10.3390/nu12020333. View

16.

Conlon M, Bird A . The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014; 7(1):17-44. PMC: 4303825. DOI: 10.3390/nu7010017. View

17.

Gesualdo L, Di Leo V, Coppo R . The mucosal immune system and IgA nephropathy. Semin Immunopathol. 2021; 43(5):657-668. PMC: 8551125. DOI: 10.1007/s00281-021-00871-y. View

18.

Ueda H, Shibahara N, Takagi S, Inoue T, Katsuoka Y . AST-120, an oral adsorbent, delays the initiation of dialysis in patients with chronic kidney diseases. Ther Apher Dial. 2007; 11(3):189-95. DOI: 10.1111/j.1744-9987.2007.00430.x. View

19.

Laudadio I, Fulci V, Palone F, Stronati L, Cucchiara S, Carissimi C . Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome. OMICS. 2018; 22(4):248-254. DOI: 10.1089/omi.2018.0013. View

20.

Vanholder R, Schepers E, Pletinck A, Nagler E, Glorieux G . The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J Am Soc Nephrol. 2014; 25(9):1897-907. PMC: 4147984. DOI: 10.1681/ASN.2013101062. View