The state of the intestinal microbial-tissue complex in patients with chronic kidney disease

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The gut microbiota plays a fundamental role in maintaining normal organism homeostasis, regulating a wide range of metabolic, biosynthetic, and immune functions. This complex ecosystem, together with cellular, and stromal components of the intestinal wall, forms the intestinal microbial-tissue complex, which pathology is considered a universal mechanism for the development of many diseases, including chronic kidney disease. Accumulation of nitrogen metabolism products in the intestine, specific diet, polypharmacy, sedentary lifestyle, limited fluid intake, and violation of gastrointestinal motility in patients with chronic kidney disease lead to a decrease in the number of bacteria synthesizing short-chain fatty acids with crucial physiological effects, along with an increase in the content of anaerobic proteolytic bacteria expressing uricase, urease, and p-cresol-, and indole-forming enzymes. The features of gut dysbiosis depend on the etiology of chronic kidney disease and severity of renal insufficiency and differ significantly in individuals receiving various renal replacement therapies (hemodialysis, peritoneal dialysis, kidney transplant recipients). Abnormal microbial metabolism enhances the production and accumulation of microbial-derived uremic toxins: p-cresyl sulfate, indoxyl sulfate, and trimethylamine-N-oxide. Renal insufficiency, through mechanisms mainly associated with the hydrolysis of accumulated in the lumen of the intestine urea, leads to inflammation, and swelling of the intestinal wall, which is accompanied by disorders of the immune tolerance of the mucous layer and disorganization of intercellular junctional complexes, which are critical modulators of intestinal intercellular transepithelial transport. Uremia-induced impairment of the gut epithelial barrier integrity induces the systemic translocation of numerous immunogenic substances generated by the aberrant microbiota, followed by the development of oxidative stress and chronic subclinical inflammation that causes the progression of chronic kidney disease and related complications. The most pronounced changes were observed in people with end-stage chronic kidney disease. Further study of the bidirectional relationship between the kidneys and intestinal microbial-tissue complex will contribute to the development of new directions of pathogenetic therapy and prevention of adverse outcomes in patients with chronic kidney disease.

Full Text

Restricted Access

About the authors

Mikhail O. Pyatchenkov

Kirov Military Medical Academy

Author for correspondence.
Email: pyatchenkovMD@yandex.ru
ORCID iD: 0000-0002-5893-3191
SPIN-code: 5572-8891

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Svetlana P. Salikova

Kirov Military Medical Academy

Email: salikova.1966@bk.ru
ORCID iD: 0000-0003-4839-9578
SPIN-code: 2012-8481

MD, Dr. Sci. (Med.), associate professor

Russian Federation, Saint Petersburg

Evgeniy V. Sherbakov

Kirov Military Medical Academy

Email: evgenvmeda@mail.ru
ORCID iD: 0000-0002-3045-1721
SPIN-code: 6337-6039

nephrologist

Russian Federation, Saint Petersburg

Andrey A. Vlasov

Kirov Military Medical Academy

Email: vlasovandrej@mail.ru
ORCID iD: 0000-0002-7915-3792
SPIN-code: 2801-1228

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

References

  1. Tkachenko EI, Grinevich VB, Gubonina IV, et al. Disease as a result of violations of the symbiotic relationship between the host and the microbiota with pathogens. Bulletin of the Russian Military Medical Academy. 2021;23(2):243–252. (In Russ.). doi: 10.17816/brmma58117
  2. Pyatchenkov MO, Markov AG, Rumyantsev AS. Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part I. Nephrology (Saint-Petersburg). 2022;26(1):10–26. (In Russ.). doi: 10.36485/1561-6274-2022-26-1-10-26
  3. Pyatchenkov MO, Rumyantsev AS, Sherbakov EV, Markov AG. Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part II. Nephrology (Saint-Petersburg). 2022;26(2):46–64. (In Russ.). doi: 10.36485/1561-6274-2022-26-2-46-64
  4. Jager KJ, Kovesdy C, Langham R, et al. A single number for advocacy and communication-worldwide more than 850 million individuals have kidney diseases. Nephrol Dial Transplant. 2019;34(11):1803–1805. doi: 10.1093/ndt/gfz174
  5. Bhargava S, Merckelbach E, Noels H, et al. Homeostasis in the Gut Microbiota in Chronic Kidney Disease. Toxins (Basel). 2022;14(10):648. doi: 10.3390/toxins14100648
  6. Wilkins LJ, Monga M, Miller AW. Defining Dysbiosis for a Cluster of Chronic Diseases. Sci Rep. 2019;9(1):12918. doi: 10.1038/s41598-019-49452-y
  7. Li F, Wang M, Wang J, et al. Alterations to the Gut Microbiota and Their Correlation With Inflammatory Factors in Chronic Kidney Disease. Front Cell Infect Microbiol. 2019;9:206. doi: 10.3389/fcimb.2019.00206
  8. Monteiro RC, Rafeh D, Gleeson PJ. Is There a Role for Gut Microbiome Dysbiosis in IgA Nephropathy? Microorganisms. 2022;10(4):683. doi: 10.3390/microorganisms10040683
  9. Shah NB, Nigwekar SU, Kalim S, et al. The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls. Kidney360. 2021;2(8):1261–1274. doi: 10.34067/KID.0000132021
  10. Tao S, Li L, Li L, et al. Understanding the gut-kidney axis among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition. Acta Diabetol. 2019;56(5):581–592. doi: 10.1007/s00592-019-01316-7
  11. Du X, Liu J, Xue Y, et al. Alteration of gut microbial profile in patients with diabetic nephropathy. Endocrine. 2021;73(1):71–84. doi: 10.1007/s12020-021-02721-1
  12. Azzouz D, Omarbekova A, Heguy A, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis. 2019;78(7):947–956. doi: 10.1136/annrheumdis-2018-214856
  13. Hu X, Ouyang S, Xie Y, et al. Characterizing the gut microbiota in patients with chronic kidney disease. Postgrad Med. 2020;132(6): 495–505. doi: 10.1080/00325481.2020.1744335
  14. Chung S, Barnes JL, Astroth KS. Gastrointestinal Microbiota in Patients with Chronic Kidney Disease: A Systematic Review. Adv Nutr. 2019;10(5):888–901. doi: 10.1093/advances/nmz028
  15. Zhao J, Ning X, Liu B, et al. Specific alterations in gut microbiota in patients with chronic kidney disease: an updated systematic review. Ren Fail. 2021;43(1):102–112. doi: 10.1080/0886022X.2020.1864404
  16. Vaziri N, Wong J, Pahl M, et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013;83(2):308–315. doi: 10.1038/ki.2012.345
  17. Stadlbauer V, Horvath A, Ribitsch W, et al. Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis. Sci Rep. 2017;7(1):15601. doi: 10.1038/s41598-017-15650-9
  18. Crespo-Salgado J, Vehaskari VM, Stewart T, et al. Intestinal microbiota in pediatric patients with end stage renal disease: a Midwest Pediatric Nephrology Consortium study. Microbiome. 2016;4(1):50. doi: 10.1186/s40168-016-0195-9
  19. Salvadori M, Tsalouchos A. Microbiota, renal disease and renal transplantation. World J Transplant. 2021;11(3):16–36. doi: 10.5500/wjt.v11.i3.16
  20. Wong J, Piceno YM, DeSantis TZ, et al. Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. Am J Nephrol. 2014;39(3):230–237. doi: 10.1159/000360010
  21. Jiang S, Xie S, Lv D, et al. A reduction in the butyrate producing species Roseburia spp. and Faecalibacterium prausnitzii is associated with chronic kidney disease progression. Antonie Van Leeuwenhoek. 2016;109(10):389–1396. doi: 10.1007/s10482-016-0737-y
  22. Sun C-Y, Lin C-J, Pan H-C, et al. Clinical association between the metabolite of healthy gut microbiota, 3-indolepropionic acid and chronic kidney disease. Clin Nutr. 2019;38(6):2945–2948. doi: 10.1016/j.clnu.2018.11.029
  23. Vaziri ND, Yuan J, Nazertehrani S, et al. Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction. Am J Nephrol. 2013;38(2):99–103. doi: 10.1159/000353764
  24. Vaziri ND, Yuan J, Norris K. Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. Am J Nephrol. 2013;37(1):1–6. doi: 10.1159/000345969
  25. Gonzalez A, Krieg R, Massey HD, et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant. 2019;34(5):783–794. doi: 10.1093/ndt/gfy238
  26. de Almeida Duarte JB, de Aguilar-Nascimento JE, Nascimento M, Nochi RJ Jr. Bacterial translocation in experimental uremia. Urol Res. 2004;32(4):266–270. doi: 10.1007/s00240-003-0381-7
  27. Wang F, Jiang H, Shi K, et al. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton). 2012;17(8):733–738. doi: 10.1111/j.1440-1797.2012.01647.x
  28. Okada K, Sekino M, Funaoka H, et al. Intestinal fatty acid-binding protein levels in patients with chronic renal failure. J Surg Res. 2018;230:94–100. doi: 10.1016/j.jss.2018.04.057
  29. Guijarro-Muñoz I, Compte M, Álvarez-Cienfuegos A, et al. Lipopolysaccharide activates Toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway and proinflammatory response in human pericytes. J Biol Chem. 2014;289(4):2457–2468. doi: 10.1074/jbc.M113.521161
  30. McIntyre CW, Harrison LEA, Eldehni MT, et al. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(1):133–141. doi: 10.2215/CJN.04610510
  31. Guo S, Al-Sadi R, Said HM, Ma TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol. 2013;182(2):375–387. doi: 10.1016/j.ajpath.2012.10.014
  32. Pedruzzi LM, Stockler-Pinto MB, Leite M Jr, Mafra D. Nrf2-keap1 system versus NF-κB: the good and the evil in chronic kidney disease? Biochimie. 2012;94(12):2461–2466. doi: 10.1016/j.biochi.2012.07.015
  33. Sun C-Y, Chang S-C, Wu M-S. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS One. 2012;7(3):e34026. doi: 10.1371/journal.pone.0034026
  34. Miyazaki T, Ise M, Seo H, Niwa T. Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys. Kidney Int Suppl. 1997;62:15–22.
  35. Ichii O, Otsuka-Kanazawa S, Nakamura T, et al. Podocyte injury caused by indoxyl sulfate, a uremic toxin and aryl-hydrocarbon receptor ligand. PLoS One. 2014;9(9):e108448. doi: 10.1371/journal.pone.0108448
  36. Wu I-W, Hsu K-H, Lee C-C, et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011;26(3):938–947. doi: 10.1093/ndt/gfq580
  37. Watanabe H, Miyamoto Y, Honda D, et al. p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int. 2013;83(4):582–592. doi: 10.1038/ki.2012.448
  38. Joossens M, Faust K, Gryp T, et al. Gut microbiota dynamics and uraemic toxins: one size does not fit all. Gut. 2019;68(12):2257–2260. doi: 10.1136/gutjnl-2018-317561
  39. Tang WWH, Wang Z, Kennedy DJ, et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448–455. doi: 10.1161/CIRCRESAHA.116.305360
  40. de Brito JS, Borges NA, dos Anjos JS, et al. Aryl Hydrocarbon Receptor and Uremic Toxins from the Gut Microbiota in Chronic Kidney Disease Patients: Is There a Relationship between Them? Biochemistry. 2019;58(15):2054–2060. doi: 10.1021/acs.biochem.8b01305
  41. Harlacher E, Wollenhaupt J, Baaten C, Noels H. Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review. Int J Mol Sci. 2022;23(1):531. doi: 10.3390/ijms23010531
  42. Foresto-Neto O, Ghirotto B, Câmara NOS. Renal Sensing of Bacterial Metabolites in the Gut-kidney Axis. Kidney360. 2021;2(9):1501–1509. doi: 10.34067/KID.0000292021

Supplementary files

There are no supplementary files to display.


Copyright (c) 2023 Eco-Vector



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies