The role of gut dysbiosis in endocrine and metabolic derangements of chronic kidney disease: mechanisms, controversies, and future perspectives.

Chronic kidney disease (CKD) is increasingly recognized as a systemic endocrine-metabolic disorder in which gut dysbiosis acts as a key amplifier of disease progression and complications. This mini-review summarizes current evidence linking alterations in gut microbial composition and function to major endocrine and metabolic derangements in CKD. Dysbiosis promotes the accumulation of gut-derived uremic toxins, including indoxyl sulphate, p-cresyl sulphate, and trimethylamine N-oxide, while reducing beneficial metabolites such as short-chain fatty acids, vitamin K, and protective tryptophan derivatives. Through interconnected pathways involving inflammation, oxidative stress, endothelial injury, immune dysregulation, and disturbed inter-organ signalling, these changes contribute to chronic kidney disease-mineral and bone disorder, vascular calcification, insulin resistance, protein-energy wasting, anaemia, and cognitive dysfunction. We further discuss major controversies, including the context-dependent role of trimethylamine N-oxide, the contested operational definition of "dysbiosis," and the clinical balance between low-protein dietary strategies and the risk of malnutrition, as well as the role of dietary fibre and whole-diet patterns. Practical diet-related approaches that translate these mechanistic findings into clinical practice are also outlined. Current limitations include incomplete mechanistic validation, limited longitudinal and interventional data, and inadequate integration of multi-omics approaches. Overall, available evidence suggests that gut dysbiosis is not simply a consequence of renal impairment, but a mechanistically relevant and potentially modifiable mediator of endocrine and metabolic complications in CKD. A better understanding of microbiota-metabolite-host interactions may support precision nutrition and microbiota-targeted therapies for risk stratification and treatment in renal endocrinology.