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Background <p>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.</p> Methods <p>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.</p> Results <p>SCFA-producing bacteria were significantly reduced in CKD patients (<i>P</i> &lt; 0.001). Butyric acid was negatively correlated with p-cresyl sulfate (rₛ=-0.423, <i>P</i> &lt; 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.</p> Conclusions <p>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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Mengzhe Wang,
  • Yumeng Li,
  • Zixuan Fu,
  • Yuheng Liu,
  • Yingge He,
  • Changqing Gao,
  • Yaling Li,
  • Huina Wu,
  • Yongchang Yuan,
  • Liyu Chen,
  • Liqi Li

摘要

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.