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粪便微生物群移植可调节小鼠模型中髓源性抑制细胞并减轻肾纤维化。

Fecal microbiota transplantation modulates myeloid-derived suppressor cells and attenuates renal fibrosis in a murine model.

作者信息

Wang Yajie, Chen Yuye, Xiao Zihao, Shi Yuanhui, Fu Cong, Cao Yuhan

机构信息

Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.

Anesthesia Laboratory and Training Center of Wannan Medical College, Wuhu, Anhui, China.

出版信息

Ren Fail. 2025 Dec;47(1):2480749. doi: 10.1080/0886022X.2025.2480749. Epub 2025 Mar 26.

DOI:10.1080/0886022X.2025.2480749
PMID:40141007
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11951334/
Abstract

BACKGROUND

Renal fibrosis is a hallmark of progressive chronic kidney disease (CKD), with emerging evidence linking gut microbiota dysbiosis to disease progression. Myeloid-derived suppressor cells (MDSCs) have demonstrated renoprotective effects, yet the impact of fecal microbiota transplantation (FMT) on MDSC-mediated modulation of renal fibrosis remains unclear.

METHODS

C57BL/6J mice underwent unilateral ureteral obstruction (UUO) to induce renal fibrosis, followed by FMT administration gavage. Flow cytometry was used to quantify granulocytic (G-MDSCs) and monocytic (M-MDSCs) MDSC populations in peripheral blood, kidney, and spleen. To elucidate the role of MDSCs in FMT-mediated effects, MDSCs were depleted or adoptively transferred . Renal fibrosis severity and inflammatory cytokine expression were subsequently analyzed.

RESULTS

FMT altered MDSC distribution, increasing M-MDSC accumulation in the blood and kidney. This was associated with downregulation of proinflammatory cytokines and attenuation of renal fibrosis. Adoptive MDSC transfer similarly produced anti-inflammatory and antifibrotic effects, reinforcing their therapeutic role in FMT-mediated renal protection.

CONCLUSIONS

FMT enhances M-MDSC-mediated immunomodulation, reducing inflammation and renal fibrosis in UUO-induced CKD. These findings suggest a potential therapeutic strategy targeting the gut-kidney axis in CKD management.

摘要

背景

肾纤维化是进行性慢性肾脏病(CKD)的一个标志,越来越多的证据表明肠道微生物群失调与疾病进展有关。髓系来源的抑制细胞(MDSCs)已显示出肾脏保护作用,但粪便微生物群移植(FMT)对MDSC介导的肾纤维化调节的影响仍不清楚。

方法

对C57BL/6J小鼠进行单侧输尿管梗阻(UUO)以诱导肾纤维化,随后通过灌胃给予FMT。采用流式细胞术对外周血、肾脏和脾脏中的粒细胞(G-MDSCs)和单核细胞(M-MDSCs)MDSC群体进行定量。为了阐明MDSCs在FMT介导的效应中的作用,对MDSCs进行清除或过继转移。随后分析肾纤维化严重程度和炎性细胞因子表达。

结果

FMT改变了MDSC的分布,增加了血液和肾脏中M-MDSC的积聚。这与促炎细胞因子的下调和肾纤维化的减轻有关。过继转移MDSC同样产生抗炎和抗纤维化作用,加强了它们在FMT介导的肾脏保护中的治疗作用。

结论

FMT增强了M-MDSC介导的免疫调节,减少了UUO诱导的CKD中的炎症和肾纤维化。这些发现提示了一种在CKD管理中靶向肠-肾轴的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/217dd9f4cde2/IRNF_A_2480749_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/f35c55faea45/IRNF_A_2480749_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/b3c523e43696/IRNF_A_2480749_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/6ba1c70d71ff/IRNF_A_2480749_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/9a77806389c1/IRNF_A_2480749_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/f68894a0905a/IRNF_A_2480749_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/217dd9f4cde2/IRNF_A_2480749_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/f35c55faea45/IRNF_A_2480749_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/b3c523e43696/IRNF_A_2480749_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/6ba1c70d71ff/IRNF_A_2480749_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/9a77806389c1/IRNF_A_2480749_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/f68894a0905a/IRNF_A_2480749_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa4/11951334/217dd9f4cde2/IRNF_A_2480749_F0006_C.jpg

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本文引用的文献

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Protocol for oral fecal gavage to reshape the gut microbiota in mice.通过口服粪便灌胃重塑小鼠肠道菌群的实验方案。
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Monocytic Myeloid-Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells Through IL-15 Secretion.单核细胞来源的髓系抑制细胞通过分泌白细胞介素-15抑制间充质干细胞向肌成纤维细胞分化。
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Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression Regulation of CCL5-CCR5 Axis.髓源性抑制细胞缓解肾纤维化进展:CCL5-CCR5 轴的调节。
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New Tricks for Old Friends: Treating Gut Microbiota of Patients With CKD.老朋友的新把戏:治疗慢性肾脏病患者的肠道微生物群
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