Phosphate binders and the gut microbiota in chronic kidney disease: mechanisms, mixed evidence, and clinical considerations.

Chronic kidney disease (CKD) disrupts the gut microbiome through dietary restrictions, uraemia, and polypharmacy, including phosphate binders. This dysbiosis contributes to systemic inflammation, accumulation of uremic toxins, and reduced short-chain fatty acid (SCFA)-producing bacteria. Hyperphosphatemia, a key CKD complication, typically emerges in advanced stages. This review examines the impact of phosphate binders on gut microbiota and explores emerging biological therapies. Phosphate binders are standard treatment for hyperphosphatemia but may influence gut microbiota by altering luminal pH, intestinal transit, and availability of metabolites such as SCFAs and vitamin K. These changes can impair gut barrier integrity and promote inflammation. Evidence on their microbiome effects is mixed: some studies show minimal compositional changes with calcium acetate or sucroferric oxyhydroxide, while others report individual variability and subtle taxon-specific shifts, particularly with iron-based binders. Even when compositional changes are limited, certain binders may modulate uremic toxin levels. Given the limitations of conventional therapies, biological approaches such as probiotics, synbiotics, and phosphate-accumulating organisms (PAOs) are gaining interest. These strategies may reduce intestinal phosphate availability by lowering pH, enhancing calcium-phosphate binding, and promoting microbial phosphate uptake and storage, while supporting gut barrier function. Overall, current evidence remains heterogeneous and limited by small cohorts and preclinical designs. Although microbiota-targeted therapies show mechanistic promise, robust clinical trials are needed before they can be recommended beyond adjunctive use.