Review
BibTex RIS Cite

Kronik Böbrek Hastalıklarında Prebiyotik Kullanımının Hastalık Progresyonu Üzerine Etkileri

Year 2024, Issue: 23, 968 - 982, 31.08.2024

Abstract

Kronik böbrek hastalığı (KBH), böbrek fonksiyonunun ilerleyici ve geri dönüşsüz kaybıyla karakterize bir klinik sendromdur. KBH ile bağırsak mikrobiyotasındaki değişiklikler arasında karşılıklı ve karmaşık bir ilişki bulunmakla birlikte her ikisi de birbirini etkileyebilmektedir. KBH’de intestinal geçişin yavaşlaması, belirli ilaçların tekrarlayan kullanımı, diyet kısıtlamaları, amonyak ve ürenin bağırsağa sekresyonu gibi çeşitli faktörler disbiyozise neden olmaktadır. Bağırsak bariyer geçirgenliğinin artması, üremik toksin öncülerinin dolaşıma girmesini kolaylaştırabilir. Artan üremik toksin seviyeleri, hafif-orta dereceli KBH ve kronik böbrek yetmezliği olan hastalarda tüm nedenlere bağlı ölüm ve kardiyovasküler hastalık (KVH) riskini artırabilir. Prebiyotikler, yararlı bakterilerin büyümesini ve aktivitesini artıran sindirilmeyen besin bileşenleridir. Yapılan birçok çalışma, prebiyotiklerin bağırsak bakteri kompozisyonunu modüle edebileceğini ve aynı zamanda inflamasyonu, oksidatif stresi ve apoptozu azaltarak böbrek hasarı ve işlev bozukluğuna karşı koruyucu etkiler gösterebileceğini öne sürmektedir. Bu nedenle prebiyotikler, KBH olan bireyler için düşük maliyetli, sağlık açısından faydalı ve invazif olmayan bir tedavi seçeneği olarak gündeme gelmiştir. Bu derlemede, KBH'de prebiyotik kullanımının hastalığın ilerlemesi üzerindeki etkileri özetlenmiştir.

References

  • 1. Esgalhado M, Kemp JA, Damasceno NR, Fouque D, Mafra D. Short-chain fatty acids: A link between prebiotics and microbiota in chronic kidney disease. Future Microbiol. 2017;12:1413-1425. doi: 10.2217/fmb-2017-0059.
  • 2. Bryniarski MA, Hamarneh F, Yacoub R. The role of chronic kidney disease-associated dysbiosis in cardiovascular disease. Exp Biol Med (Maywood). 2019;244(6):514-525. doi: 10.1177/1535370219826526.
  • 3. Rukavina Mikusic NL, Kouyoumdzian NM, Choi MR. Gut microbiota and chronic kidney disease: Evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis. Pflugers Arch. 2020;472(3):303-320. doi: 10.1007/s00424-020-02352-x.
  • 4. Huang Y, Xin W, Xiong J, Yao M, Zhang B, Zhao J. The intestinal microbiota and metabolites in the gut-kidney-heart axis of chronic kidney disease. Front Pharmacol. 2022;13:837500. doi: 10.3389/fphar.2022.837500.
  • 5. Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014;25(4):657-670. doi: 10.1681/ASN.2013080905.
  • 6. Lau WL, Vaziri ND. The leaky gut and altered microbiome in chronic kidney disease. J Ren Nutr. 2017;27(6):458-461. doi: 10.1053/j.jrn.2017.02.010
  • 7. Sumida K, Pierre JF, Yuzefpolskaya M, Colombo PC, Demmer RT, Kovesdy CP. Gut microbiota-targeted interventions in the management of chronic kidney disease. Semin Nephrol. 2023;43(2):151408. doi: 10.1016/j.semnephrol.2023.151408.
  • 8. Ramos CI, Armani RG, Canziani MEF, et al. Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial. Nephrol Dial Transplant. 2019;34(11):1876-1884. doi: 10.1093/ndt/gfy171.
  • 9. Armani RG, Carvalho AB, Ramos CI, et al. Effect of fructooligosaccharide on endothelial function in CKD patients: A randomized controlled trial. Nephrol Dial Transplant. 2021;37(1):85-91. doi: 10.1093/ndt/gfaa335.
  • 10. Melekoglu E, Cetinkaya MA, Kepekci-Tekkeli SE, Kul O, Samur G. Effects of prebiotic oligofructose-enriched inulin on gut-derived uremic toxins and disease progression in rats with adenine-induced chronic kidney disease. PLoS One. 2021;16(10):e0258145. doi: 10.1371/journal.pone.0258145.
  • 11. Rysz J, Franczyk B, Ławiński J, Olszewski R, Ciałkowska-Rysz A, Gluba-Brzózka A. The Impact of CKD on uremic toxins and gut microbiota. Toxins (Basel). 2021;13(4):252. doi: 10.3390/toxins13040252.
  • 12. Tain YL, Hsu CN. Role of the gut microbiota in children with kidney disease. Children (Basel). 2023;10(2):269. doi: 10.3390/children10020269.
  • 13. Chen YY, Chen DQ, Chen L, et al. Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease. J Transl Med. 2019;17(1):5. doi: 10.1186/s12967-018-1756-4.
  • 14. Wehedy E, Shatat IF, Al Khodor S. The human microbiome in chronic kidney disease: A double-edged sword. Front Med (Lausanne). 2022;8:790783. doi: 10.3389/fmed.2021.790783.
  • 15. Sabatino A, Regolisti G, Cosola C, Gesualdo L, Fiaccadori E. Intestinal microbiota in Type 2 diabetes and chronic kidney disease. Curr Diab Rep. 2017;17(3):16. doi: 10.1007/s11892-017-0841-z.
  • 16. Jazani NH, Savoj J, Lustgarten M, Lau WL, Vaziri ND. Impact of gut dysbiosis on neurohormonal pathways in chronic kidney disease. Diseases. 2019;7(1):21. doi: 10.3390/diseases7010021.
  • 17. Zhao J, Ning X, Liu B, Dong R, Bai M, Sun S. 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.
  • 18. Jiang S, Xie S, Lv D, et al. Alteration of the gut microbiota in Chinese population with chronic kidney disease. Sci Rep. 2017;7(1):2870. doi: 10.1038/s41598-017-02989-2.
  • 19. Hu Q, Wu K, Pan W, et al. Intestinal flora alterations in patients with early chronic kidney disease: A case-control study among the Han population in southwestern China. J Int Med Res. 2020;48(6):300060520926033. doi: 10.1177/0300060520926033.
  • 20. 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):349-355. doi: 10.1159/000189334.
  • 21. Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. 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.
  • 22. Vaziri ND, 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.
  • 23. Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM. Chronic kidney disease and the gut microbiome. Am J Physiol Renal Physiol. 2019;316(6):F1211-F1217. doi: 10.1152/ajprenal.00298.2018.
  • 24. Stubbs JR, House JA, Ocque AJ, et al. Serum trimethylamine-n-oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J Am Soc Nephrol. 2016;27(1):305-313. doi: 10.1681/ASN.2014111063.
  • 25. Wojtaszek E, Oldakowska-Jedynak U, Kwiatkowska M, Glogowski T, Malyszko J. Uremic toxins, oxidative stress, atherosclerosis in chronic kidney disease, and kidney transplantation. Oxid Med Cell Longev. 2021;2021:6651367. doi: 10.1155/2021/6651367
  • 26. Hsu CN, Tain YL. Chronic kidney disease and gut microbiota: What is their connection in early life? Int J Mol Sci. 2022;23(7):3954. doi: 10.3390/ijms23073954.
  • 27. Wang X, Zhang P, Zhang X. Probiotics regulate gut microbiota: An effective method to improve immunity. Molecules. 2021;26(19):6076. doi: 10.3390/molecules26196076.
  • 28. Oniszczuk A, Oniszczuk T, Gancarz M, Szymańska J. Role of gut microbiota, probiotics and prebiotics in the cardiovascular diseases. Molecules. 2021;26(4):1172. doi: 10.3390/molecules26041172.
  • 29. Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics-a step beyond pre- and probiotics. Nutrients. 2020;12(8):2189. doi: 10.3390/nu12082189.
  • 30. Zirker L. Benefit and use of prebiotics in patients with chronic kidney disease. Journal of Renal Nutrition. 2015;25:9-10. doi: 10.1053/j.jrn.2014.12.007.
  • 31. Iwashita Y, Ohya M, Yashiro M, et al. Dietary changes involving bifidobacterium longum and other nutrients delays chronic kidney disease progression. Am J Nephrol. 2018;47(5):325-332. doi: 10.1159/000488947.
  • 32. Vaziri ND, Liu SM, Lau WL, et al. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS One. 2014;9(12):e114881. doi: 10.1371/journal.pone.0114881.
  • 33. Hung TV, Suzuki T. Dietary fermentable fibers attenuate chronic kidney disease in mice by protecting the intestinal barrier. J Nutr. 2018;148(4):552-561. doi: 10.1093/jn/nxy008.
  • 34. Kieffer DA, Piccolo BD, Vaziri ND, et al. Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats. Am J Physiol Renal Physiol. 2016;310(9):F857-F871. doi: 10.1152/ajprenal.00513.2015.
  • 35. Poesen R, Evenepoel P, de Loor H, et al. The influence of prebiotic arabinoxylan oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: A randomized controlled trial. PLoS One. 2016;11(4):e0153893. doi: 10.1371/journal.pone.0153893.
  • 36. Ebrahim Z, Proost S, Tito RY, et al. The effect of ß-glucan prebiotic on kidney function, uremic toxins and gut microbiome in stage 3 to 5 chronic kidney disease (CKD) predialysis participants: A randomized controlled trial. Nutrients. 2022;14(4):805. doi: 10.3390/nu14040805.
  • 37. Tayebi Khosroshahi H, Habibzadeh A, Khoshbaten M, Rahbari B, Chaichi P, Badiee AH. Lactulose for reduction of nitrogen products in patients with chronic kidney disease. Iran J Kidney Dis. 2014;8(5):377-381.
  • 38. Esgalhado M, Kemp JA, Azevedo R, et al. Could resistant starch supplementation improve inflammatory and oxidative stress biomarkers and uremic toxins levels in hemodialysis patients? A pilot randomized controlled trial. Food Funct. 2018;9(12):6508-6516. doi: 10.1039/c8fo01876f.
  • 39. McFarlane C, Ramos CI, Johnson DW, Campbell KL. Prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease: A systematic review and meta-analysis. J Ren Nutr. 2019;29(3):209-220. doi: 10.1053/j.jrn.2018.08.008.
  • 40. Tayebi-Khosroshahi H, Habibzadeh A, Niknafs B, et al. The effect of lactulose supplementation on fecal microflora of patients with chronic kidney disease: A randomized clinical trial. Journal of Renal Injury Prevention. 2016;5(3):162-7. doi: 10.15171/jrip.2016.34.

Effects of Prebiotic Use on Disease Progression in Chronic Kidney Diseases

Year 2024, Issue: 23, 968 - 982, 31.08.2024

Abstract

Chronic kidney disease (CKD) is a clinical syndrome characterized by progressive and irreversible loss of kidney function. While there exists a mutual and complex relationship between CKD and changes in the gut microbiota, both can influence each other. Various factors such as slowing of intestinal transit, repeated use of certain medications, dietary restrictions, and secretion of ammonia and urea into the intestine cause dysbiosis in CKD. Increased intestinal barrier permeability may facilitate the entry of uremic toxin precursors into the circulation. Increased uremic toxin levels may increase the risk of all-cause death and cardiovascular disease (CVD) in patients with mild-to-moderate CKD and chronic renal failure. Prebiotics are non-digestible food ingredients that increase the growth and activity of beneficial bacteria. Several studies have shown that prebiotics can modulate intestinal bacterial composition and also exert protective effects against kidney damage and dysfunction by reducing inflammation, oxidative stress and apoptosis. Therefore, prebiotics have emerged as a low-cost, health-beneficial and non-invasive treatment option for individuals with CKD. This review summarizes the effect of prebiotic use in chronic kidney disease on disease progression.

References

  • 1. Esgalhado M, Kemp JA, Damasceno NR, Fouque D, Mafra D. Short-chain fatty acids: A link between prebiotics and microbiota in chronic kidney disease. Future Microbiol. 2017;12:1413-1425. doi: 10.2217/fmb-2017-0059.
  • 2. Bryniarski MA, Hamarneh F, Yacoub R. The role of chronic kidney disease-associated dysbiosis in cardiovascular disease. Exp Biol Med (Maywood). 2019;244(6):514-525. doi: 10.1177/1535370219826526.
  • 3. Rukavina Mikusic NL, Kouyoumdzian NM, Choi MR. Gut microbiota and chronic kidney disease: Evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis. Pflugers Arch. 2020;472(3):303-320. doi: 10.1007/s00424-020-02352-x.
  • 4. Huang Y, Xin W, Xiong J, Yao M, Zhang B, Zhao J. The intestinal microbiota and metabolites in the gut-kidney-heart axis of chronic kidney disease. Front Pharmacol. 2022;13:837500. doi: 10.3389/fphar.2022.837500.
  • 5. Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol. 2014;25(4):657-670. doi: 10.1681/ASN.2013080905.
  • 6. Lau WL, Vaziri ND. The leaky gut and altered microbiome in chronic kidney disease. J Ren Nutr. 2017;27(6):458-461. doi: 10.1053/j.jrn.2017.02.010
  • 7. Sumida K, Pierre JF, Yuzefpolskaya M, Colombo PC, Demmer RT, Kovesdy CP. Gut microbiota-targeted interventions in the management of chronic kidney disease. Semin Nephrol. 2023;43(2):151408. doi: 10.1016/j.semnephrol.2023.151408.
  • 8. Ramos CI, Armani RG, Canziani MEF, et al. Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: A randomized controlled trial. Nephrol Dial Transplant. 2019;34(11):1876-1884. doi: 10.1093/ndt/gfy171.
  • 9. Armani RG, Carvalho AB, Ramos CI, et al. Effect of fructooligosaccharide on endothelial function in CKD patients: A randomized controlled trial. Nephrol Dial Transplant. 2021;37(1):85-91. doi: 10.1093/ndt/gfaa335.
  • 10. Melekoglu E, Cetinkaya MA, Kepekci-Tekkeli SE, Kul O, Samur G. Effects of prebiotic oligofructose-enriched inulin on gut-derived uremic toxins and disease progression in rats with adenine-induced chronic kidney disease. PLoS One. 2021;16(10):e0258145. doi: 10.1371/journal.pone.0258145.
  • 11. Rysz J, Franczyk B, Ławiński J, Olszewski R, Ciałkowska-Rysz A, Gluba-Brzózka A. The Impact of CKD on uremic toxins and gut microbiota. Toxins (Basel). 2021;13(4):252. doi: 10.3390/toxins13040252.
  • 12. Tain YL, Hsu CN. Role of the gut microbiota in children with kidney disease. Children (Basel). 2023;10(2):269. doi: 10.3390/children10020269.
  • 13. Chen YY, Chen DQ, Chen L, et al. Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease. J Transl Med. 2019;17(1):5. doi: 10.1186/s12967-018-1756-4.
  • 14. Wehedy E, Shatat IF, Al Khodor S. The human microbiome in chronic kidney disease: A double-edged sword. Front Med (Lausanne). 2022;8:790783. doi: 10.3389/fmed.2021.790783.
  • 15. Sabatino A, Regolisti G, Cosola C, Gesualdo L, Fiaccadori E. Intestinal microbiota in Type 2 diabetes and chronic kidney disease. Curr Diab Rep. 2017;17(3):16. doi: 10.1007/s11892-017-0841-z.
  • 16. Jazani NH, Savoj J, Lustgarten M, Lau WL, Vaziri ND. Impact of gut dysbiosis on neurohormonal pathways in chronic kidney disease. Diseases. 2019;7(1):21. doi: 10.3390/diseases7010021.
  • 17. Zhao J, Ning X, Liu B, Dong R, Bai M, Sun S. 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.
  • 18. Jiang S, Xie S, Lv D, et al. Alteration of the gut microbiota in Chinese population with chronic kidney disease. Sci Rep. 2017;7(1):2870. doi: 10.1038/s41598-017-02989-2.
  • 19. Hu Q, Wu K, Pan W, et al. Intestinal flora alterations in patients with early chronic kidney disease: A case-control study among the Han population in southwestern China. J Int Med Res. 2020;48(6):300060520926033. doi: 10.1177/0300060520926033.
  • 20. 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):349-355. doi: 10.1159/000189334.
  • 21. Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S. 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.
  • 22. Vaziri ND, 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.
  • 23. Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM. Chronic kidney disease and the gut microbiome. Am J Physiol Renal Physiol. 2019;316(6):F1211-F1217. doi: 10.1152/ajprenal.00298.2018.
  • 24. Stubbs JR, House JA, Ocque AJ, et al. Serum trimethylamine-n-oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J Am Soc Nephrol. 2016;27(1):305-313. doi: 10.1681/ASN.2014111063.
  • 25. Wojtaszek E, Oldakowska-Jedynak U, Kwiatkowska M, Glogowski T, Malyszko J. Uremic toxins, oxidative stress, atherosclerosis in chronic kidney disease, and kidney transplantation. Oxid Med Cell Longev. 2021;2021:6651367. doi: 10.1155/2021/6651367
  • 26. Hsu CN, Tain YL. Chronic kidney disease and gut microbiota: What is their connection in early life? Int J Mol Sci. 2022;23(7):3954. doi: 10.3390/ijms23073954.
  • 27. Wang X, Zhang P, Zhang X. Probiotics regulate gut microbiota: An effective method to improve immunity. Molecules. 2021;26(19):6076. doi: 10.3390/molecules26196076.
  • 28. Oniszczuk A, Oniszczuk T, Gancarz M, Szymańska J. Role of gut microbiota, probiotics and prebiotics in the cardiovascular diseases. Molecules. 2021;26(4):1172. doi: 10.3390/molecules26041172.
  • 29. Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics-a step beyond pre- and probiotics. Nutrients. 2020;12(8):2189. doi: 10.3390/nu12082189.
  • 30. Zirker L. Benefit and use of prebiotics in patients with chronic kidney disease. Journal of Renal Nutrition. 2015;25:9-10. doi: 10.1053/j.jrn.2014.12.007.
  • 31. Iwashita Y, Ohya M, Yashiro M, et al. Dietary changes involving bifidobacterium longum and other nutrients delays chronic kidney disease progression. Am J Nephrol. 2018;47(5):325-332. doi: 10.1159/000488947.
  • 32. Vaziri ND, Liu SM, Lau WL, et al. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS One. 2014;9(12):e114881. doi: 10.1371/journal.pone.0114881.
  • 33. Hung TV, Suzuki T. Dietary fermentable fibers attenuate chronic kidney disease in mice by protecting the intestinal barrier. J Nutr. 2018;148(4):552-561. doi: 10.1093/jn/nxy008.
  • 34. Kieffer DA, Piccolo BD, Vaziri ND, et al. Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats. Am J Physiol Renal Physiol. 2016;310(9):F857-F871. doi: 10.1152/ajprenal.00513.2015.
  • 35. Poesen R, Evenepoel P, de Loor H, et al. The influence of prebiotic arabinoxylan oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: A randomized controlled trial. PLoS One. 2016;11(4):e0153893. doi: 10.1371/journal.pone.0153893.
  • 36. Ebrahim Z, Proost S, Tito RY, et al. The effect of ß-glucan prebiotic on kidney function, uremic toxins and gut microbiome in stage 3 to 5 chronic kidney disease (CKD) predialysis participants: A randomized controlled trial. Nutrients. 2022;14(4):805. doi: 10.3390/nu14040805.
  • 37. Tayebi Khosroshahi H, Habibzadeh A, Khoshbaten M, Rahbari B, Chaichi P, Badiee AH. Lactulose for reduction of nitrogen products in patients with chronic kidney disease. Iran J Kidney Dis. 2014;8(5):377-381.
  • 38. Esgalhado M, Kemp JA, Azevedo R, et al. Could resistant starch supplementation improve inflammatory and oxidative stress biomarkers and uremic toxins levels in hemodialysis patients? A pilot randomized controlled trial. Food Funct. 2018;9(12):6508-6516. doi: 10.1039/c8fo01876f.
  • 39. McFarlane C, Ramos CI, Johnson DW, Campbell KL. Prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease: A systematic review and meta-analysis. J Ren Nutr. 2019;29(3):209-220. doi: 10.1053/j.jrn.2018.08.008.
  • 40. Tayebi-Khosroshahi H, Habibzadeh A, Niknafs B, et al. The effect of lactulose supplementation on fecal microflora of patients with chronic kidney disease: A randomized clinical trial. Journal of Renal Injury Prevention. 2016;5(3):162-7. doi: 10.15171/jrip.2016.34.
There are 40 citations in total.

Details

Primary Language Turkish
Subjects Clinical Nutrition
Journal Section Articles
Authors

Bahar Yalçın 0000-0003-4036-7096

Şebnem Özgen Özkaya 0000-0002-4358-8321

Early Pub Date August 31, 2024
Publication Date August 31, 2024
Submission Date February 13, 2024
Acceptance Date August 5, 2024
Published in Issue Year 2024 Issue: 23

Cite

JAMA Yalçın B, Özgen Özkaya Ş. Kronik Böbrek Hastalıklarında Prebiyotik Kullanımının Hastalık Progresyonu Üzerine Etkileri. IGUSABDER. 2024;:968–982.

 Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)