Ponad 7000 publikacji medycznych!
Statystyki za 2021 rok:
odsłony: 8 805 378
Artykuły w Czytelni Medycznej o SARS-CoV-2/Covid-19

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu tutaj
© Borgis - Postępy Nauk Medycznych 9/2016, s. 659-663
*Alicja Rydzewska-Rosołowska1, Katarzyna Kakareko1, Mariusz Rosołowski2, Tomasz Hryszko1, Szymon Brzósko1, Michał Myśliwiec1, Beata Naumnik1
Microbiome and the kidney
Mikrobiom w chorobach nerek
11st Department of Nephrology and Transplantation with Dialysis Unit, Medical University in Białystok
Head of Department: Professor Beata Naumnik, MD, PhD
2Department of Gastroenterology and Internal Medicine, Medical University in Białystok
Head of Department: Professor Andrzej Dąbrowski, MD, PhD
Jelito człowieka jest zasiedlone przez ogromną ilość mikroorganizmów wywierających wpływ m.in. na metabolizm oraz odporność organizmu gospodarza. W ostatnich latach pojawiają się coraz liczniejsze doniesienia o roli zaburzeń flory jelitowej w różnorakich schorzeniach, w tym także w chorobach nerek. Badacze sugerują udział mikrobiomu w patogenezie i/lub progresji takich chorób jak nadciśnienie, nefropatia IgA, ostre uszkodzenie nerek, kamica nerkowa czy też przewlekła choroba nerek. Ponadto modulacja układu odpornościowego przez bakterie jelitowe prawdopodobnie ma znaczenie wśród pacjentów po przeszczepieniu nerki. Istnienie związku pomiędzy mikrobiomem a chorobami nerek stwarza potencjalne nowe możliwości terapeutyczne przy wykorzystaniu m.in. prebiotyków, probiotyków czy też synbiotyków. Badania z ostatnich lat sugerują korzystny wpływ takiej interwencji na zahamowanie dalszego rozwoju chorób dzięki odbudowaniu fizjologicznej mikroflory bakteryjnej. Ze względu na nieliczne dane konieczne są dalsze badania oceniające skuteczność takiej interwencji.
W niniejszej pracy przedstawiamy aktualne doniesienia o roli mikrobiomu w nefrologii oraz omawiamy nowe potencjalne możliwości terapeutyczne w chorobach nerek uwzględniające jego zaburzenia.
The human gut is home to a very complex environment comprising of tremendous amount of microbes (mainly bacteria but also archaea, viruses and eukaryotes). In the few recent years there has been a growing interest in the role of gut bacteria in health and disease. This has resulted in linking gut microbiome with a variety of disorders, kidney diseases among others. Indeed, recent studies have discovered a potential impact of colonic bacteria on development and/or progression of multiple renal diseases, including hypertension, IgA nephropathy, acute kidney injury, chronic kidney disease and nephrolithiasis. Moreover due to its importance in the modulation of immune system, microbiome plays a role in kidney transplantation. The discovery of relationship between colonic bacteria and renal pathophysiology create a potential therapeutic target. Novel strategies to rebuild intestinal symbiosis involve prebiotics, probiotics and synbiotics. Recent studies have provided encouraging data that these new opportunities may have a therapeutic role in improving outcome of patients with kidney diseases. Further investigation is needed to entirely elucidate the functions of the microbiome and assess efficacy of microbiome oriented interventions.
This review will focus on the potential role of gut microbiome in nephrology and discus the new emerging concept of microbiome targeted therapeutic intervention in management of renal diseases.
The gut microbiota exist in a symbiotic relationship with the human organism. Under physiologic conditions, interactions between the gut microbiome and the host contribute to maintain normal nutrition, metabolism and immune function (1, 2). Great progress in characterizing the structure of microbiome has led to highlight the role of colon bacteria in health and in disease. Disturbances in normal gut microbiota is called dysbiosis and growing evidence is linking dysbiosis with pathogenesis of multiple diseases, including kidney diseases. In this review we will focus on the potential role of gut microbiome in nephrology and discus the new emerging concept of microbiome targeted therapeutic interventions in management of renal diseases.
Human microbiome in health
The human gut is home to a very complex environment comprising of approximately 1 kg of microbes (mainly bacteria but also archaea, viruses and eukaryotes). Genes within those organisms are termed the microbiome.
In the few recent years there has been a tremendous interest in the role of gut bacteria in health and disease. This has resulted in two large projects aiming to characterize the human microbiome: the European Metagenomic of the Human Intestinal Tract (MetaHIT) (3) and the Human Microbiome Project (HMP) (4). MetaHIT catalogued 3.3 million microbial genes (from a cohort of 124 European individuals) – 150-fold more than the human gene complement (3), HMP obtained samples from 300 American individuals (4). In 2014 the aforementioned data were combined with that from a Chinese project resulting in an integrated gene catalogue comprising of more than 9 million genes (5). Findings from these studies suggest that each and every person harbours a unique ecosystem of microbes which has the potential to change adaptively to our needs (depending on the surrounding environment, diet) and greatly influences our well-being. On average we host a few hundred species, mainly bacterial, with the predominant ones being Bacteroidetes, Firmicutes and Actinobacteria (6).
At birth the colon (where the microbiome is most abundant) is largely sterile (although some bacteria can be transmitted from the mother during pregnancy (7)). Bacterial colonization occurs during birth (especially vaginal) and continues afterwards depending on many factors (antibiotic treatment, mode of feeding etc.). The microbiome resembles that of an adult before the third year of age, remains relatively stable (8) and plays an important role in the development of the nervous system and immune response. It also participates in the synthesis of vitamins (vitamin K), degradation of dietary oxalates (Oxalobacter formigenes), indigestible plant polysaccharides, metabolism of bile acids (9).
Human microbiome and kidney disease
The impact of gut microbiome on kidney diseases is a novel area of interest – PubMed search reveals 77 publications with the keywords gut microbiome and kidney disease, of which only 3 are older than 5 years. The impact of colonic bacteria on renal pathophysiology seems to be ubiquitous as suggested by more and more data each day.
Hypertension is probably also influenced by the composition of the human microbiome through gastrointestinal sodium handling (10), modification of expression of hypertensive phenotype (11) and other mechanisms. Recent studies have shown that both in rat models of hypertension and in a small sample of patients there is a decrease in the microbial abundance, diversity and an increased Firmicutes/Bacteroidetes ratio. A microbiome-oriented intervention (minocycline in this case) reduces blood pressure suggesting a therapeutic possibility (12). Another new study reveals a relationship between gut dysbiosis and blood pressure in obstructive sleep apnea-induced hypertension (13).
IgA nephropathy
IgA nephropathy (IgAN) has also been associated with intestinal immunity (IgA is present in mucosal secretions – gastrointestinal fluid). Studies show that the microbiome composition is different in patients with IgA nephropathy and healthy controls and also in patients in which disease progresses and non-progressors (14). In animal models B-cell activation factor transgenic mice were shown to exhibit IgA mesangial deposition which did not occur without the presence of specific gut microbiota and circulation of specific IgA antibodies (15). Genome-wide association studies suggest a tight link between IgAN and inflammatory bowel diseases (16) therefore strengthening the hypothesis for a strong intestine-kidney connection possibly mediated by the gut microbiome.
Acute kidney injury
In animal models of kidney ischemia-reperfusion injury the extent of damage differs between germ-free and control mice being more severe in “sterile” animals and becoming equivalent after addition of bacteria to diet suggesting a potential therapeutic intervention (17).
Another acute kidney injury (AKI) study evaluated the relationship between short-chain fatty acids (SCFAs) and the extent of renal dysfunction. In health SCFAs are fermentation end products (derived from dietary fiber) of gut microbiota which exhibit anti-inflammatory properties. Mice subjected to ischemia-reperfusion injury treated with butyrate, propionate and acetate 30 minutes before ischemia and at the moment of reperfusion which modulated the inflammatory process, ameliorated the effects of hypoxia and improved outcomes (18).
Chronic kidney disease
The emerging role of gut bacteria in chronic kidney disease (CKD), which has been termed “kidney-gut axis” or “microbiome-centric theory of CKD progression” (19, 20), has been gaining importance in recent years. The fact that some of the uremic toxins are of colonic origin and that in the face of disease the gut excretes some metabolites e.g. potassium has been known for years.

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
  • Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
  • Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
  • Aby kupić kod proszę skorzystać z jednej z poniższych opcji.

Opcja #1


  • dostęp do tego artykułu
  • dostęp na 7 dni

uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony

Opcja #2


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 30 dni
  • najpopularniejsza opcja

Opcja #3


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 90 dni
  • oszczędzasz 28 zł
Bäckhed F, Ley RE, Sonnenburg JL et al.: Host-bacterial mutualism in the human intestine. Science 2005; 307(5717): 1915-1920.
Hooper LV, Midtvedt T, Gordon JI: How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 2002; 22: 283-307.
Qin J, Li R, Raes J et al.: A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464(7285): 59-65.
Aagaard K, Petrosino J, Keitel W et al.: The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J 2013; 27(3): 1012-1022.
Lee JR, Muthukumar T, Dadhania D et al.: Gut microbial community structure and complications after kidney transplantation: a pilot study. Transplantation 2014; 98(7): 697-705.
Eckburg PB, Bik EM, Bernstein CN et al.: Diversity of the human intestinal microbial flora. Science 2005; 308(5728): 1635-1638.
Funkhouser LJ, Bordenstein SR: Mom knows best: the universality of maternal microbial transmission. PLoS Biol 2013; 11(8): e1001631.
Lim ES, Zhou Y, Zhao G et al.: Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat Med 2015; 21(10): 1228-1234.
Ramezani A, Raj DS: The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol 2014; 25(4): 657-670.
Furness JB, Rivera LR, Cho HJ et al.: The gut as a sensory organ. Nat Rev Gastroenterol Hepatol 2013; 10(12): 729-740.
Pluznick JL, Protzko RJ, Gevorgyan H et al.: 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): 4410-4415.
Yang T, Santisteban MM, Rodriguez V et al.: Gut dysbiosis is linked to hypertension. Hypertension 2015; 65(6): 1331-1340.
Durgan DJ, Ganesh BP, Cope JL et al.: Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension. Hypertension 2016; 67(2): 469-474.
De Angelis M, Montemurno E, Piccolo M et al.: Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN). PLoS One 2014; 9(6): e99006.
McCarthy DD, Kujawa J, Wilson C et al.: Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest 2011; 121(10): 3991-4002.
Kiryluk K, Li Y, Scolari F et al.: Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 2014; 46(11): 1187-1196.
Jang HR, Gandolfo MT, Ko GJ et al.: Early exposure to germs modifies kidney damage and inflammation after experimental ischemia-reperfusion injury. Am J Physiol Renal Physiol 2009; 297(5): F1457-1465.
Andrade-Oliveira V, Amano MT, Correa-Costa M et al.: Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion. J Am Soc Nephrol 2015; 26(8): 1877-1888.
Meijers BK, Evenepoel P: The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant 2011; 26(3): 759-761.
Nallu A, Sharma S, Ramezani A et al.: Gut microbiome in chronic kidney disease: challenges and opportunities. Transl Res 2016 Apr 30; pii: S1931-5244(16)30033-0. DOI: 10.1016/j.trsl.2016.04.007.
Simenhoff ML, Dunn SR, Zollner GP et al.: Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus. Miner Electrolyte Metab 1996; 22(1-3): 92-96.
Vaziri ND, Wong J, Pahl M et al.: Chronic kidney disease alters intestinal microbial flora. Kidney Int 2013; 83(2): 308-315.
Gibson SA, McFarlan C, Hay S, MacFarlane GT: Significance of microflora in proteolysis in the colon. Appl Environ Microbiol 1989; 55(3): 679-683.
Aronov PA, Luo FJ, Plummer NS et al.: Colonic contribution to uremic solutes. J Am Soc Nephrol 2011; 22(9): 1769-1776.
Vaziri ND, Dure-Smith B, Miller R, Mirahmadi MK: Pathology of gastrointestinal tract in chronic hemodialysis patients: an autopsy study of 78 cases. Am J Gastroenterol 1985; 80(8): 608-611.
Wu MJ, Chang CS, Cheng CH et al.: Colonic transit time in long-term dialysis patients. Am J Kidney Dis 2004; 44(2): 322-327.
Kalantar-Zadeh K, Kopple JD, Deepak S et al.: Food intake characteristics of hemodialysis patients as obtained by food frequency questionnaire. J Ren Nutr 2002; 12(1): 17-31.
Jernberg C, Löfmark S, Edlund C, Jansson JK: Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 2010; 156(Pt 11): 3216-3223.
Werner T, Wagner SJ, Martínez I et al.: Depletion of luminal iron alters the gut microbiota and prevents Crohn’s disease-like ileitis. Gut 2011; 60(3): 325-333.
Satoh M, Hayashi H, Watanabe M et al.: Uremic toxins overload accelerates renal damage in a rat model of chronic renal failure. Nephron Exp Nephrol 2003; 95(3): e111-118.
Barrios C, Beaumont M, Pallister T et al.: Gut-Microbiota-Metabolite Axis in Early Renal Function Decline. PLoS One 2015; 10(8): e0134311.
Poesen R, Ramezani A, Claes K et al.: Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD. Clin J Am Soc Nephrol 2015; 10(9): 1525-1533.
Cani PD, Amar J, Iglesias MA et al.: Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56(7): 1761-1772.
Wu X, Ma C, Han L et al.: Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol 2010; 61(1): 69-78.
Perna AF, Lanza D, Sepe I et al.: Hydrogen sulfide, a toxic gas with cardiovascular properties in uremia: how harmful is it? Blood Purif 2011; 31(1-3): 102-106.
Aminzadeh MA, Vaziri ND: Downregulation of the renal and hepatic hydrogen sulfide (H2S)-producing enzymes and capacity in chronic kidney disease. Nephrol Dial Transplant 2012; 27(2): 498-504.
Perna AF, Luciano MG, Ingrosso D et al.: Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes. Nephrol Dial Transplant 2009; 24(12): 3756-3763.
Mu C, Yang Y, Zhu W: Gut Microbiota: The Brain Peacekeeper. Front Microbiol 2016; 7: 345.
Lathrop SK, Bloom SM, Rao SM et al.: Peripheral education of the immune system by colonic commensal microbiota. Nature 2011; 478(7368): 250-254.
Lee JR, Muthukumar T, Dadhania D et al.: Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS One 2015; 10(3): e0122399.
Stern JM, Moazami S, Qiu Y et al.: Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers. Urolithiasis 2016 Apr 26 [Epub ahead of print].
Meijers BK, De Preter V, Verbeke K et al.: p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrol Dial Transplant 2010; 25(1): 219-224.
Evenepoel P, Bammens B, Verbeke K, Vanrenterghem Y: Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney Int 2006; 70(1): 192-198.
Krishnamurthy VM, Wei G, Baird BC et al.: High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease. Kidney Int 2012; 81(3): 300-306.
Food and Agriculture Organization: Guidelines for the Evaluation of Probiotics in Food Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food. Food and Agriculture Organization, London 2002.
Prakash S, Chang TM: Microencapsulated genetically engineered live E. coli DH5 cells administered orally to maintain normal plasma urea level in uremic rats. Nat Med 1996; 2(8): 883-887.
Ranganathan N, Patel BG, Ranganathan P et al.: In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. ASAIO J 2006; 52(1): 70-79.
Ranganathan N, Ranganathan P, Friedman EA et al.: Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv Ther 2010; 27(9): 634-647.
Miranda Alatriste PV, Urbina Arronte R, Gómez Espinosa CO, Espinosa Cuevas M de L: Effect of probiotics on human blood urea levels in patients with chronic renal failure. Nutr Hosp 2014; 29(3): 582-590.
Hida M, Aiba Y, Sawamura S et al.: 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.
Takayama F, Taki K, Niwa T: Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis. Am J Kidney Dis 2003; 41(3 suppl. 1): S142-S145.
Natarajan R, Pechenyak B, Vyas U et al.: Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed Res Int 2014; 2014: 568571.
Rossi M, Johnson DW, Morrison M et al.: Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. Clin J Am Soc Nephrol 2016; 11(2): 223-231.
Ponziani FR, Scaldaferri F, Petito V et al.: The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin. Dig Dis 2016; 34(3): 269-278.
Stubbs J: Rifaximin Therapy in Chronic Kidney Disease. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- (cited 2016 Aug 30). Available from: https://clinicaltrials.gov/ct2/show/NCT02342639 NLM Identifier: NCT02342639.
Kelly CR, Khoruts A, Staley C et al.: Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial. Ann Intern Med 2016. DOI: 10.7326/M16-0271.
Sun PP, Perianayagam MC, Jaber BL: Sevelamer hydrochloride use and circulating endotoxin in hemodialysis patients: a pilot cross-sectional study. J Ren Nutr 2009; 19(5): 432-438.
Hatakeyama S, Yamamoto H, Okamoto A et al.: Effect of an Oral Adsorbent, AST-120, on Dialysis Initiation and Survival in Patients with Chronic Kidney Disease. Int J Nephrol 2012; 2012: 376128.
Cha RH, Kang SW, Park CW et al.: A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction. Clin J Am Soc Nephrol 2016; 11(4): 559-567.
Mishima E, Fukuda S, Shima H et al.: Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD. J Am Soc Nephrol 2015; 26(8): 1787-1794.
otrzymano: 2016-08-04
zaakceptowano do druku: 2016-08-25

Adres do korespondencji:
*Alicja Rydzewska-Rosołowska
1st Department of Nephrology and Transplantation with Dialysis Unit Medical University in Białystok
ul. Żurawia 14, 15-540 Białystok
tel. +48 (85) 740-94-58
fax +48 (85) 743-45-86

Postępy Nauk Medycznych 9/2016
Strona internetowa czasopisma Postępy Nauk Medycznych

Pozostałe artykuły z numeru 9/2016: