The gut–kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics

Sep 29, 2026

Uploaded by Callum

Chronic kidney disease (CKD) remains a major global health problem, marked by persistent diagnostic and therapeutic difficulties. Conventional biomarkers like serum creatinine and eGFR have well-recognized limitations, driving demand for novel diagnostic tools and interventions. This review synthesizes how the gut–kidney axis—shaped by microbial dysbiosis and altered metabolite production—contributes to CKD pathogenesis. Harmful uremic metabolites promote inflammation, endothelial dysfunction, and fibrosis, while protective short-chain fatty acids support barrier integrity and immune regulation. It evaluates microbiome-targeted approaches, including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation, considering efficacy, safety, and translational readiness.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

1 Introduction and rationale

Gut–kidney axis and uremic metabolites

Dysbiosis across pediatric and adult CKD

Microbiome-targeted therapies and clinical variability

OPEN ACCESS EDITED BY Marijn M. Speeckaert, Ghent University Hospital, Belgium REVIEWED BY İsmail Mert Vural, University of Health Sciences (Turkey), Türkiye Xiangyu Zou, Shanghai Children’s Hospital, China *CORRESPONDENCE Sami Alobaidi [salobaidi@uj.edu.sa](salobaidi@uj.edu.sa) RECEIVED 29 July 2025 REVISED 02 December 2025 ACCEPTED 04 December 2025 PUBLISHED 23 December 2025 CITATION Alobaidi S (2025) The gut–kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics. Front. Med. 12:1675458 . doi: 10.3389/fmed.2025.1675458 COPYRIGHT © 2025 Alobaidi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Review PUBLISHED 23 December 2025 DOI 10.3389/fmed.2025.1675458 The gut–kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics Sami Alobaidi* Department of Internal Medicine, University of Jeddah, Jeddah, Saudi Arabia Chronic kidney disease (CKD) remains a major global health issue, affecting millions and presenting persistent diagnostic and therapeutic challenges. Conventional biomarkers such as serum creatinine and estimated glomerular filtration rate have well-recognized limitations, underscoring the need for novel diagnostic tools and interventions. Emerging evidence highlights the gut–kidney axis as a central contributor to CKD pathogenesis, shaped by microbial dysbiosis and altered metabolite production. Harmful metabolites such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide promote inflammation, endothelial dysfunction, and fibrosis, while loss of protective short-chain fatty acids impairs barrier integrity and immune regulation. This review integrates mechanistic, translational, clinical, and therapeutic perspectives, offering a comprehensive and distinctive synthesis of current knowledge. We emphasize both harmful and protective microbial metabolites, incorporate the often-overlooked oral–gut–kidney axis, and highlight advances in multi-omics and computational approaches for biomarker discovery. Microbiome-targeted interventions—including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation—are critically evaluated with respect to efficacy, safety, and translational readiness. By bridging basic science, clinical evidence, and therapeutic implications, this review provides a forward-looking framework for integrating microbiome insights into CKD diagnosis and management. Our synthesis complements existing literature while highlighting unmet needs, thereby informing future research priorities and guiding the development of clinically relevant microbiome-based strategies. KEYWORDS chronic kidney disease, dysbiosis, fecal microbiota transplantation, gut microbiota, gut– kidney axis, microbiome-targeted therapy, trimethylamine N-oxide, uremic toxins 1 Introduction and rationale Chronic kidney disease (CKD) is a significant global health concern, currently affecting approximately 9.1% of the global population, corresponding to approximately 697 million individuals, with substantial contributions to morbidity, mortality, and healthcare costs ( 1). Early detection of CKD remains difficult due to limitations of conventional diagnostic tools. Serum creatinine and estimated glomerular filtration rate (eGFR), common indicators of kidney function, are significantly influenced by age, sex, and muscle mass, thereby reducing their accuracy, especially during CKD’s initial stages (2, 3). These limitat

FAQs

Why are conventional CKD biomarkers such as serum creatinine and eGFR limited?

They are influenced by age, sex, and muscle mass, which reduces accuracy, particularly in early CKD. The review highlights the resulting need for better biomarkers and advanced diagnostic methods.

How does the gut–kidney axis contribute to CKD progression?

CKD-associated uremia disrupts intestinal balance, while gut-derived microbial metabolites further drive kidney damage, inflammation, and fibrosis. Dysbiosis increases toxin-producing bacteria and raises uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and TMAO.

What microbiome-targeted interventions are discussed, and how is their effectiveness evaluated?

The review evaluates dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation. It emphasizes assessing efficacy, safety, and translational readiness, noting that outcomes can vary across interventions.

Sep 29, 2026

Uploaded by Callum