The Gut–Kidney Axis in Feline Chronic Kidney Disease: A Systematic Review of Microbiome Dysbiosis and Translational Therapeutic Implications within a One Health Framework

Abstract

Chronic kidney disease (CKD) in cats is a progressive condition commonly associated with irreversible nephron loss, chronic low-grade inflammation, and retention of uremic solutes, particularly protein-bound toxins. In recent years, increasing attention has been directed toward the gut–kidney axis as a potential contributor to disease progression, mainly through microbial metabolites and host–microbiome interactions that may influence systemic homeostasis.This systematic review summarizes current evidence on gut microbiome alterations in feline CKD and explores their potential role in uremic toxin production, inflammatory signaling pathways, and emerging microbiome-based therapeutic strategies.A structured literature search was conducted in PubMed, Scopus, and Web of Science to identify studies evaluating gut microbiome composition and function in cats with CKD. Observational, experimental, and interventional studies were included when reporting microbial diversity, uremic toxins, inflammatory biomarkers, or microbiome-targeted therapies. The review followed PRISMA guidelines for study selection and synthesis.Across available studies, feline CKD is consistently associated with gut dysbiosis characterized by reduced microbial diversity and depletion of commensal bacteria involved in short-chain fatty acid production. In contrast, an increased abundance of proteolytic and urease-producing taxa is frequently reported. These changes are associated with higher circulating levels of uremic toxins such as indoxyl sulfate and p-cresyl sulfate, which have been linked to oxidative stress, endothelial dysfunction, and chronic inflammation. Although evidence remains limited and heterogeneous, preliminary studies suggest that dietary modification, probiotics, and prebiotics may reduce uremic toxin burden and partially improve metabolic and inflammatory parameters.Overall, current evidence supports a biologically relevant gut–kidney axis in feline CKD. However, heterogeneity in study design and limited controlled data prevent firm conclusions regarding therapeutic efficacy. Further well-designed longitudinal studies are needed to clarify the clinical potential of microbiome modulation in feline CKD management.