FIGURE 1.

Gut microbiome dysbiosis as a potential trigger for metabolic dysfunction-associated kidney disease (MDAKD). The diagram depicts the potential association between gut microbiota dysbiosis and the onset of metabolic dysfunction-associated kidney disease (MDAKD), as outlined in the article. Alterations in gut microbiota composition may facilitate the release of lipopolysaccharides (LPS), thereby intensifying chronic inflammation. Variations in the concentrations of short-chain fatty acids (SCFAs), bile acids (BAs), and branched-chain amino acids (BCAAs) can disrupt lipid and glucose metabolism, leading to obesity, insulin resistance, and type 2 diabetes. Additionally, increased trimethylamine N-oxide (TMAO) levels and impaired blood pressure regulation by SCFAs may contribute to the development of cardiovascular disease and heart failure (HF). These metabolic disorders subsequently promote MDAKD through mechanisms such as endothelial dysfunction, adipose tissue remodeling, impaired renal tubular function, and activation of the renin-angiotensin-aldosterone system (RAAS). MDAKD is characterized by glomerular hyperfiltration, podocyte injury, and parenchymal fibrosis. Moreover, microbiota-derived metabolites, including indoxyl sulfate (IS) and p-cresyl sulfate (pCS), may contribute to kidney injury. Elevated urea and ammonia levels observed in chronic kidney disease (CKD) further increase intestinal permeability, thereby worsening adverse alterations in the gut microbiota. Abbreviations: MDAKD, metabolic dysfunction-associated kidney disease; LPS, lipopolysaccharide; SCFAs, short-chain fatty acids; BAs, bile acids; BCAAs, branched-chain amino acids; TMAO, trimethylamine N-oxide; IS, indoxyl sulfate; pCS, p-cresyl sulfate; HF, heart failure; RAAS, renin–angiotensin–aldosterone system; CKD, chronic kidney disease.