Gut-Kidney Axis: Novel Insights in Kidney Diseases

Chem Biodivers. 2025 Dec;22(12):e01506. doi: 10.1002/cbdv.202501506. Epub 2025 Sep 11.

Abstract

Chronic kidney disease (CKD) is increasingly prevalent worldwide, and its management is an urgent issue. Understanding of its pathophysiology and the development of new treatment methods are critical. In recent years, gut microbiota reportedly contributes to the homeostasis of systemic organs and the pathogenesis of diseases. Also, in kidney disease, alterations in the gut microbiota (dysbiosis) have been observed and are deeply involved in pathophysiology. d-Amino acids derived from gut microbiota change in concentration in the body concomitant with dysbiosis. d-Serine and d-alanine have been shown to have renal tubular protective effects in acute tubular necrosis, suggesting their potential as renal therapeutic agents. We have been evaluating the therapeutic effects of d-alanine, metabolic enzyme inhibitors, and food products containing d-amino acids in human CKD. The recent association between gut and systemic organ dysfunction not only reveals new mechanisms of disease but also indicates the possibility of new therapeutic strategies. This article provides an overview of new insights into kidney disease, gut microbiota, and its metabolites.

Keywords: d‐amino acid; gut microbiota; kidney diseases; leaky gut.

Publication types

  • Review

MeSH terms

  • Animals
  • Dysbiosis
  • Gastrointestinal Microbiome*
  • Humans
  • Kidney Diseases* / metabolism
  • Kidney* / metabolism
  • Renal Insufficiency, Chronic* / metabolism