The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2021 Jun 7

PMID 34095319

Citations 41

Authors

Mingxuan Chi

Kuai Ma

Jing Wang

Zhaolun Ding

Yunlong Li

Shaomi Zhu

Xin Liang

Qinxiu Zhang

Linjiang Song

Chi Liu

Affiliations

Soon will be listed here.

Abstract

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

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References

Bakris G, Agarwal R, Chan J, Cooper M, Gansevoort R, Haller H . Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA. 2015; 314(9):884-94. DOI: 10.1001/jama.2015.10081. View

Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal W, Strowig T . Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012; 482(7384):179-85. PMC: 3276682. DOI: 10.1038/nature10809. 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

Shaheen V, Satoh M, Richards H, Yoshida H, Shaw M, Jennette J . Immunopathogenesis of environmentally induced lupus in mice. Environ Health Perspect. 1999; 107 Suppl 5:723-7. PMC: 1566261. DOI: 10.1289/ehp.99107s5723. View

Pluznick J, Protzko R, Gevorgyan H, Peterlin Z, Sipos A, Han J . Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013; 110(11):4410-5. PMC: 3600440. DOI: 10.1073/pnas.1215927110. View

Tanaka H, Takechi M, Kiyonari H, Shioi G, Tamura A, Tsukita S . Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice. Gut. 2015; 64(10):1529-38. DOI: 10.1136/gutjnl-2014-308419. View

Litinskiy M, Nardelli B, Hilbert D, He B, Schaffer A, Casali P . DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002; 3(9):822-9. PMC: 4621779. DOI: 10.1038/ni829. View

Ichii O, Otsuka-Kanazawa S, Nakamura T, Ueno M, Kon Y, Chen W . Podocyte injury caused by indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand. PLoS One. 2014; 9(9):e108448. PMC: 4171541. DOI: 10.1371/journal.pone.0108448. View

McIntyre C, Harrison L, Eldehni M, Jefferies H, Szeto C, John S . Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol. 2010; 6(1):133-41. PMC: 3022234. DOI: 10.2215/CJN.04610510. View

10.

Huang Y, Wongamorntham S, Kasting J, McQuillan D, Owens R, Yu L . Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms. Kidney Int. 2005; 69(1):105-13. DOI: 10.1038/sj.ki.5000011. View

11.

Ivanov I, de Llanos Frutos R, Manel N, Yoshinaga K, Rifkin D, Sartor R . Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008; 4(4):337-49. PMC: 2597589. DOI: 10.1016/j.chom.2008.09.009. View

12.

Faith J, Guruge J, Charbonneau M, Subramanian S, Seedorf H, Goodman A . The long-term stability of the human gut microbiota. Science. 2013; 341(6141):1237439. PMC: 3791589. DOI: 10.1126/science.1237439. View

13.

De Angelis M, Montemurno E, Piccolo M, Vannini L, Lauriero G, Maranzano V . Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN). PLoS One. 2014; 9(6):e99006. PMC: 4055632. DOI: 10.1371/journal.pone.0099006. View

14.

Abboud H, Henrich W . Clinical practice. Stage IV chronic kidney disease. N Engl J Med. 2010; 362(1):56-65. DOI: 10.1056/NEJMcp0906797. View

15.

Schepers E, Meert N, Glorieux G, Goeman J, Van der Eycken J, Vanholder R . P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production. Nephrol Dial Transplant. 2006; 22(2):592-6. DOI: 10.1093/ndt/gfl584. View

16.

Pluznick J . A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014; 5(2):202-7. PMC: 4063845. DOI: 10.4161/gmic.27492. View

17.

Hida M, Aiba Y, Sawamura S, Suzuki N, Satoh T, Koga Y . Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis. Nephron. 1996; 74(2):349-55. DOI: 10.1159/000189334. View

18.

Rooks M, Garrett W . Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016; 16(6):341-52. PMC: 5541232. DOI: 10.1038/nri.2016.42. View

19.

Geuking M, Cahenzli J, Lawson M, Ng D, Slack E, Hapfelmeier S . Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity. 2011; 34(5):794-806. DOI: 10.1016/j.immuni.2011.03.021. View

20.

Lai X, Zhang A, Chen S, He L, Su C, Fan M . Outcomes of stage 1-5 chronic kidney disease in Mainland China. Ren Fail. 2014; 36(4):520-5. DOI: 10.3109/0886022X.2013.875859. View