Microbiota-gut-kidney axis in health and renal disease

Jan 12, 2026International journal of biological sciences

How Gut Bacteria and Kidneys Interact in Health and Kidney Disease

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Abstract

Microbial dysbiosis may increase harmful metabolites and reduce protective ones, contributing to kidney damage.

An imbalance in gut bacteria can lead to higher levels of harmful substances like uremic toxins.
Beneficial metabolites such as short-chain fatty acids are decreased in cases of microbial dysbiosis.
The accumulation of harmful metabolites is linked to the progression of fibrosis in the kidneys.
Various pathways, including inflammatory and oxidative stress responses, mediate the effects of gut microbiota on kidney health.
Innovative therapies such as probiotics and fecal microbiota transplantation may help restore microbial balance.
Targeting gut microbiota could offer new treatment options for acute kidney injury and chronic kidney disease.

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Gut microbiota plays a central role in programming host metabolic function and immune modulation in both health and disease. Microbial dysbiosis leads to an increase in opportunistic pathogens and a reduction in beneficial bacteria, which collectively result in the excessive production of detrimental metabolites, particularly uremic toxins such as indoxyl sulfate and trimethylamine-N-oxide, while concurrently decreasing beneficial metabolites, such as short-chain fatty acids and tryptophan catabolites, including indole-3-aldehyde. The accumulation of harmful metabolites and depletion of protective metabolites contribute to fibrosis progression through various mediators, including the renin-angiotensin system, reactive oxygen species, Toll-like receptor 4, aryl hydrocarbon receptor, inhibitor of kappa B/nuclear factor kappa B, and Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathways. This review highlights the pathogenic link between gut microbiota and kidney damage via the gut-kidney axis, encompassing acute kidney injury (AKI) and chronic kidney disease (CKD). Innovative therapeutic strategies, including microbial therapeutics (such as probiotics, prebiotics, and synbiotics), natural products (such as neohesperidin, isoquercitrin, and polysaccharides), and fecal microbiota transplantation, have been proposed to restore microbial balance and improve kidney function. Targeted modulation of the gut microbiota offers a promising strategy for developing novel treatments in AKI, CKD, and the transition from AKI-to-CKD. This approach has the potential to prevent or mitigate these conditions and their complications.

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Microbiota-gut-kidney axis in health and renal disease

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