Probiotics restore enteric HDL3 secretion and improve prognosis in patients with end-stage renal disease

IF 23.7 Q1 MICROBIOLOGY

iMeta Pub Date : 2025-07-01 DOI:10.1002/imt2.70062

Xiaoxue Liu, Yuan Huang, Yixuan Li, Juan Chen, Xifan Wang, Xiaobin Wang, Liang Zhao, Yongting Luo, Peng An, Liwei Zhang, Chengying Zhang, Weijing Bian, Xingen Lei, Xiang Gao, Yinghua Liu, Yanling Hao, Huiyuan Guo, Xiaoxu Zhang, Pengjie Wang, Ran Wang, Hao Zhang, Bing Fang, Xiaolin Zhang, Longjiao Wang, Qinglu Qiu, Yuchan Zhang, Jingyi Qi, Songtao Yang, Yulong Yin, Fazheng Ren, Xiaoyu Wang

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Abstract

Randomized double-blind trials have shown that probiotic mixtures significantly increase high-density lipoprotein (HDL) levels and reduce the risk of cardiovascular disease mortality in end-stage renal disease (ESRD) patients. Meta-analysis with prospective cohort studies further confirms that elevated HDL is a protective factor for ESRD outcomes. In severe renal injury models, including 5/6 nephrectomy and apolipoprotein E-deficient (ApoE^−/−) mice, probiotics restored cardiac function, mirroring the cardioprotective effects seen in humans. Mechanistic studies indicate that probiotics enhance intestinal HDL3 production through the insulin-mediated SP1(P)-CYP27A-LXRα/β-ABCA1 pathway, thereby maintaining HDL metabolic homeostasis. This study reveals a novel link between probiotic intervention and host cholesterol metabolism, offering a previously unexplored strategy for reducing cardiovascular risk in ESRD patients.

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益生菌恢复肠内HDL3分泌，改善终末期肾病患者预后

随机双盲试验表明，益生菌混合物可显著提高终末期肾病（ESRD）患者的高密度脂蛋白（HDL）水平，降低心血管疾病死亡风险。前瞻性队列研究的荟萃分析进一步证实，HDL升高是ESRD结局的保护因素。在严重肾损伤模型中，包括5/6肾切除术和载脂蛋白e缺陷（ApoE−/−）小鼠，益生菌恢复心脏功能，反映了在人类中看到的心脏保护作用。机制研究表明，益生菌通过胰岛素介导的SP1(P)-CYP27A-LXRα/β-ABCA1途径促进肠道HDL3生成，从而维持HDL代谢稳态。本研究揭示了益生菌干预与宿主胆固醇代谢之间的新联系，为降低ESRD患者心血管风险提供了一种以前未被探索的策略。

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来源期刊

iMeta

CiteScore

10.80

自引率

0.00%

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