Short-chain fatty acids of intestinal origin attenuate protein-bound uremic toxins in patients with chronic kidney disease by protecting the intestinal barrier: a pooled analysis of multiple studies with individualized intervention strategies

BACKGROUND: Patients with chronic kidney disease (CKD) present a disordered short-chain fatty acid (SCFA)-intestinal barrier-protein-bound uremic toxin (PBUT) axis, while clinical guidelines lack strategies for PBUT source reduction. This study explored the regulatory effects of SCFAs to support individualized interventions for CKD patients. METHODS: A non-individual participant data pooled analysis was conducted on 4 studies (3 cross-sectional, 1 randomized controlled trial) including 320 CKD patients and 53 healthy controls. Correlation, mediation, subgroup, and dose-response analyses were performed to assess SCFAs, intestinal barrier, PBUTs, and renal function. RESULTS: SCFA-producing bacteria were significantly reduced in CKD patients (P < 0.001). Butyric acid was negatively correlated with p-cresyl sulfate (rₛ=-0.423, P < 0.001). The intestinal barrier mediated 37.2% of the SCFA-PBUT regulatory effect. Synbiotic and low-protein high-fiber diets optimally reduced PBUTs, with greater benefits in CKD stages 4-5 (P interaction = 0.031). High-fiber diets were safe in non-dialysis patients. CONCLUSIONS: SCFAs attenuate PBUT accumulation by protecting the intestinal barrier, which may improve CKD prognosis. Synbiotic and low-protein high-fiber diets are effective interventions, especially for advanced CKD.