The Gut–Kidney Axis: How the Microbiome Changes Across CKD, Dialysis and Transplantation
The relationship between the gut microbiome and chronic kidney disease (CKD) is becoming an increasingly important area of kidney research.
Importantly, this relationship changes as kidney disease progresses.
In earlier CKD, changes in the gut microbiome may contribute to inflammation and the production of metabolites that place additional stress on vulnerable kidneys.
As kidney function declines, the relationship becomes increasingly two-way. Rising uraemia changes the environment inside the gut, while intestinal bacteria continue producing compounds that the kidneys are progressively less able to eliminate.
During dialysis, some of these gut-derived toxins remain important because they are poorly removed by conventional haemodialysis.
Kidney transplantation changes the picture again. Uraemia improves, but immunosuppressive medications, antibiotics and changes in immune function create a different microbiome environment, with emerging research suggesting possible links between microbial activity and graft rejection.
The gut–kidney axis is therefore best understood as a dynamic relationship that changes across the different stages of kidney disease.
What Is the Gut–Kidney Axis?
The gastrointestinal tract contains a large community of microorganisms collectively known as the gut microbiome.
These organisms help metabolise components of our diet, particularly fibre and other carbohydrates that are not completely digested in the small intestine.
When fermentable fibre reaches the colon, certain bacteria produce short-chain fatty acids (SCFAs) such as butyrate, acetate and propionate.
These compounds help nourish the cells lining the bowel, support the intestinal barrier and influence immune activity.
Other microbial pathways break down amino acids from dietary protein and produce compounds that can eventually become substances such as indoxyl sulphate, p-cresyl sulphate, TMAO and phenylacetylglutamine.
Many of these compounds are normally eliminated through the kidneys. As kidney function declines, their concentrations can progressively increase.
Early-Stage CKD: The Microbiome and Inflammation
Changes in the gut microbiome can occur even in earlier stages of CKD.
Research has commonly identified lower levels of some bacteria involved in fibre fermentation and SCFA production, together with increases in organisms associated with more protein-based fermentation (Zhao et al., 2021; Voroneanu et al., 2023).
Frequently reported reductions include Roseburia, Faecalibacterium and Coprococcus, while organisms including Escherichia–Shigella and Streptococcus have been reported at higher levels in some CKD populations.
The specific organisms vary considerably between studies, and the more important question may be what the microbiome is producing.
Fibre, Short-Chain Fatty Acids and the Gut Barrier
Butyrate and other SCFAs help maintain the cells and tight junctions that form the intestinal barrier.
When fibre intake and SCFA production are reduced, this barrier may become less effective. This can increase exposure to bacterial products that promote low-grade systemic inflammation.
For someone with established kidney disease, this may add to inflammatory and oxidative stress affecting the kidneys and blood vessels.
This does not mean that gut dysbiosis is a single cause of CKD. Rather, the microbiome appears to be one of several factors capable of influencing the inflammatory and metabolic environment in which kidney disease progresses.
A gut environment favouring fibre fermentation generally produces more SCFAs. Greater reliance on protein fermentation can instead increase production of indole, p-cresol and related compounds that become increasingly difficult to eliminate as kidney function declines.
Advanced CKD: When Uraemia Changes the Gut
As kidney function declines towards stages 4 and 5, kidney disease itself begins to have a stronger effect on the intestinal environment.
One important reason is uraemia.
As blood urea rises, more urea enters the gastrointestinal tract. Certain gut bacteria break it down into ammonia and related compounds, changing the intestinal environment and potentially affecting the integrity of the gut barrier.
Advanced CKD can also influence the microbiome through:
reduced dietary variety and fibre intake
potassium and phosphorus dietary restrictions
reduced appetite
constipation and slower bowel transit
iron and phosphate-binding medications
proton-pump inhibitors
antibiotics and hospitalisation.
This can create a cycle:
declining kidney function → increasing uraemia → changes in the gut environment → dysbiosis →
greater production of uraemic toxins and inflammatory compounds → additional systemic burden
Gut-Derived Uraemic Toxins and Cardiovascular Risk
Some of the best-studied uraemic toxins begin with bacterial breakdown of amino acids.
Tryptophan can be converted by gut bacteria into indole, which is later transformed into indoxyl sulphate.
Tyrosine and phenylalanine can contribute to the formation of p-cresol and subsequently p-cresyl sulphate.
As GFR declines, the kidneys become less able to eliminate these compounds.
Higher concentrations have been associated with oxidative stress, inflammation, endothelial dysfunction, arterial stiffness and vascular injury (Chen et al., 2025).
This may be particularly important because cardiovascular disease is a major complication of advanced CKD.
The cardiovascular burden of CKD has many causes, including hypertension, diabetes, vascular calcification, anaemia, fluid overload and altered calcium and phosphorus metabolism. Gut-derived uraemic toxins appear to add another component to this broader inflammatory and vascular environment.
Can Fibre and Prebiotics Change the Gut–Kidney Axis?
This is one of the more interesting areas of current research.
Prebiotic fibres work by changing the food available to existing gut bacteria.
When more fermentable carbohydrate reaches the colon, bacterial metabolism can shift away from protein fermentation and towards carbohydrate fermentation.
This may:
increase SCFA production
support fibre-fermenting bacteria
reduce production of indole and p-cresol
increase incorporation of nitrogen into bacterial cells
increase nitrogen elimination through the bowel.
Can the Bowel Help Eliminate Nitrogen?
A small human study demonstrated this mechanism directly.
Nine people with chronic renal failure received 40 g/day of fermentable carbohydrate while consuming approximately 0.8 g/kg/day of protein.
Faecal nitrogen excretion increased by 51%, while urinary nitrogen excretion decreased and serum urea fell (Younes et al., 2006).
In simple terms, some nitrogen that would otherwise have required elimination through the kidneys was incorporated into gut bacteria and passed out through the bowel.
This has sometimes been described as ‘intestinal dialysis’, although it is quite different from haemodialysis or peritoneal dialysis.
What Do More Recent Studies Show?
A 2025 systematic review and meta-analysis combined 21 randomised controlled trials involving 700 people with CKD.
Dietary fibre supplementation significantly reduced:
indoxyl sulphate
p-cresyl sulphate
blood urea nitrogen
IL-6
TNF-α.
TMAO and high-sensitivity CRP were not significantly reduced overall (Wathanavasin et al., 2025).
A 2026 systematic review of 45 human studies reached a similar conclusion: fibre interventions commonly improved gut fermentation and reduced some uraemic toxins, while short-term effects on eGFR were generally limited or absent (Mojak and Bronkowska, 2026).
A randomised trial involving 59 people with stage 3–5 predialysis CKD also found that β-glucan supplementation reduced several uraemic toxins, although creatinine and eGFR did not significantly change during the 14-week study (Ebrahim et al., 2022).
Taken together, the evidence suggests that microbial metabolism can be changed and some gut-derived uraemic toxins can be reduced, even if an immediate improvement in kidney filtration is not seen.
Could Prebiotics Delay Dialysis?
This remains an interesting possibility, but it is not yet established.
The Gum Arabic in Renal Disease (GARDS) study followed people with progressive CKD who received 25 g/day of gum arabic, or acacia fibre, for 12 months.
During supplementation, the rate of eGFR decline was substantially slower than the participants' previous rate of kidney-function loss (Khalid et al., 2021).
The study did not include a randomised untreated control group, so the findings are promising rather than conclusive.
Research is continuing, including a randomised study examining whether gum arabic can help preserve residual kidney function in people receiving dialysis.
At present, the strongest evidence is that fermentable fibre can alter nitrogen metabolism and reduce several gut-derived uraemic toxins. Whether this can reliably extend dialysis-free time requires larger controlled trials.
Dialysis: Why the Microbiome Still Matters
Starting haemodialysis removes many waste products from the blood, but it does not remove every uraemic toxin effectively.
This is particularly important for protein-bound toxins such as indoxyl sulphate and p-cresyl sulphate.
Because these compounds bind strongly to albumin, they are less easily removed by conventional dialysis than smaller molecules such as urea.
The gut also continues producing them between dialysis treatments.
This raises an interesting possibility: rather than only trying to remove toxins after they enter the bloodstream, it may also be possible to reduce their production in the bowel.
Sirich and colleagues investigated resistant starch in people receiving maintenance haemodialysis. After six weeks, free indoxyl sulphate fell by approximately 29% in the resistant-starch group compared with almost no change in controls (Sirich et al., 2014).
An earlier study using oligofructose-enriched inulin reduced p-cresyl sulphate by around 20% in haemodialysis patients, although indoxyl sulphate was unchanged (Meijers et al., 2010).
These small studies suggest that microbiome-directed dietary strategies may complement dialysis by reducing production of some compounds that dialysis itself removes poorly.
Whether this improves cardiovascular outcomes or survival remains unknown.
Importantly, people receiving haemodialysis usually require more protein than people with advanced predialysis CKD.
Fibre intake therefore needs to be balanced with:
potassium and phosphorus levels
protein requirements
bowel function
gastrointestinal tolerance
overall nutritional status.
Maintaining regular bowel movements may also be relevant because slower intestinal transit gives bacteria more time to generate and absorb uraemic metabolites.
Kidney Transplantation: A Different Gut–Kidney Relationship
Successful kidney transplantation improves renal clearance and removes much of the uraemic environment associated with advanced kidney disease.
However, transplantation introduces new influences on the gut microbiome, including immunosuppressive medications, antibiotics, infection-prevention medications, hospitalisation and dietary changes.
The microbiome may therefore become relevant not only to metabolism but also to immune regulation and graft tolerance.
Could the Microbiome Influence Graft Rejection?
SCFAs such as butyrate and propionate influence the intestinal barrier and regulatory immune cells.
This has led researchers to investigate whether reduced SCFA-producing bacteria could be associated with an immune environment more favourable to graft rejection.
A major prospective study published in 2025 analysed 562 stool samples, including samples from 217 kidney-transplant recipients.
Before episodes of graft rejection, researchers observed reduced microbial diversity, fewer SCFA-producing bacteria and reduced microbial capacity to produce butyrate and propionate (Holle et al., 2025).
Importantly, these changes were identified before rejection occurred.
A more recent 2026 study examined the microbiome before transplantation. Among 78 recipients, those who subsequently developed biopsy-proven early acute rejection had lower levels of several microbial taxa, including Phascolarctobacterium faecium, and reduced microbial capacity for propionate production (Kim et al., 2026).
These findings do not prove that changes in the microbiome cause rejection, but they suggest an increasingly interesting relationship between intestinal microbial activity and the immune environment surrounding a transplanted kidney.
Can the Transplant Microbiome Be Modified?
An Australian double-blind randomised study tested prebiotic supplementation for seven weeks in 56 newly transplanted kidney recipients.
The intervention improved gastrointestinal symptoms, and subsequent analysis demonstrated measurable changes in the intestinal microbiome (Chan et al., 2022; Chan et al., 2024).
However, the study was not designed to determine whether prebiotics prevent graft rejection.
A Cochrane review of probiotics, prebiotics and synbiotics in solid-organ transplantation similarly concluded that evidence for improving graft outcomes, infections or organ function remains limited (Cooper et al., 2022).
The transplant microbiome is therefore an exciting area of research, but we do not yet know whether deliberately modifying it improves long-term graft outcomes.
The Gut–Kidney Axis Is One Part of the Bigger Picture
Research into the gut–kidney axis has considerably changed our understanding of kidney disease.
In earlier CKD, gut dysbiosis may add to inflammatory and metabolic stress.
As kidney function declines, uraemia increasingly changes the intestinal environment, while gut bacteria produce compounds that the kidneys struggle to eliminate.
During dialysis, some of these toxins continue to be generated despite renal replacement therapy.
Following transplantation, the relationship changes again, with increasing interest in the microbiome's influence on immune regulation and graft tolerance.
Prebiotic and fibre interventions are particularly interesting because clinical studies now show that microbial metabolism can be modified and several gut-derived uraemic toxins can be reduced.
What remains less certain is whether these changes consistently slow CKD progression, reduce cardiovascular complications, delay dialysis or improve kidney-transplant outcomes.
For now, the microbiome is best understood as one interconnected part of kidney, metabolic and immune health — and one whose role changes considerably across the stages of kidney disease.
References
Chan, S., Hawley, C.M., Pascoe, E.M., Cao, C., Campbell, S.B., Campbell, K.L., Francis, R.S., Hale, R., Isbel, N.M., Morrison, M. and Johnson, D.W. (2022) ‘Prebiotic supplementation in kidney transplant recipients for preventing infections and gastrointestinal upset: a randomized controlled feasibility study’, Journal of Renal Nutrition, 32(6), pp. 718–725. View article
Chan, S., Wood, D.L.A., Hawley, C.M. et al. (2024) ‘Characteristics of the gastrointestinal microbiota following prebiotic supplementation in acute kidney transplant recipients: results from a randomised controlled trial’, Clinical Transplantation, 38(1), e15175. View article
Chen, M-C., Kuo, C-H., Lin, Y-L. and Hsu, B-G. (2025) ‘Gut-derived uremic toxins and cardiovascular health in chronic kidney disease’, Tzu Chi Medical Journal, 37(3), pp. 264–274. View article
Cooper, T.E., Scholes-Robertson, N., Craig, J.C. et al. (2022) ‘Synbiotics, prebiotics and probiotics for solid organ transplant recipients’, Cochrane Database of Systematic Reviews, 9, CD014804. View review
Ebrahim, Z., Proost, S., Tito, R.Y., Raes, J., Glorieux, G., Moosa, M.R. and Blaauw, R. (2022) ‘The effect of β-glucan prebiotic on kidney function, uremic toxins and gut microbiome in stage 3 to 5 chronic kidney disease predialysis participants: a randomized controlled trial’, Nutrients, 14(4), 805. View article
Holle, J., Reitmeir, R., Behrens, F. et al. (2025) ‘Gut microbiome alterations precede graft rejection in kidney transplantation patients’, American Journal of Transplantation, 25(8), pp. 1643–1656. View article
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Meijers, B.K.I., De Preter, V., Verbeke, K., Vanrenterghem, Y. and Evenepoel, P. (2010) ‘p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin’, Nephrology Dialysis Transplantation, 25(1), pp. 219–224. View article
Mojak, A.G. and Bronkowska, M. (2026) ‘Dietary fibre and chronic kidney disease: a systematic review of effects on inflammation, uraemic toxins, nutritional status, kidney function, and gut–liver–kidney axis mechanisms’, Nutrients, 18(9), 1341. View article
Sirich, T.L., Plummer, N.S., Gardner, C.D., Hostetter, T.H. and Meyer, T.W. (2014) ‘Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients’, Clinical Journal of the American Society of Nephrology, 9(9), pp. 1603–1610. View article
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Younes, H., Egret, N., Hadj-Abdelkader, M., Rémésy, C., Demigné, C., Gueret, C., Deteix, P. and Alphonse, J-C. (2006) ‘Fermentable carbohydrate supplementation alters nitrogen excretion in chronic renal failure’, Journal of Renal Nutrition, 16(1), pp. 67–74. View article
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This article provides general educational information and is not intended to replace individual medical or nutritional assessment. Fibre, prebiotic and other microbiome-directed interventions need to be considered according to kidney function, potassium and phosphorus balance, medications, gastrointestinal tolerance and nutritional status. Additional caution is required during dialysis and following kidney transplantation.