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血液透析患者的肠道微生物群与NLRP3炎性小体激活:探索与全身炎症的联系

Gut microbiota and NLRP3 inflammasome activation in hemodialysis patients: exploring the link with systemic inflammation.

作者信息

Mafra Denise, Alvarenga Livia, F M F Cardozo Ludmila, Schultz Júnia, Rosado Alexandre Soares, Borges Natália A

机构信息

Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.

Fluminense Federal University (UFF), Rua Marquês de Paraná, 303/4 andar Niterói-RJ, Niterói, RJ, 24033-900, Brazil.

出版信息

Mol Biol Rep. 2025 May 19;52(1):465. doi: 10.1007/s11033-025-10562-8.

DOI:10.1007/s11033-025-10562-8
PMID:40387945
Abstract

BACKGROUND

The Nod-Like Receptor Pyrin domain-containing 3 (NLRP3) inflammasome is a critical sensor of bacterial signals and metabolites, initiating an inflammatory response. Chronic kidney disease (CKD) is often accompanied by systemic inflammation, which can be involved with gut dysbiosis. Considering this interplay, we aimed to explore the potential association between NLRP3 inflammasome expression and gut microbiota in CKD patients undergoing hemodialysis (HD).

METHODS AND RESULTS

This research comprises a cross-sectional pilot study involving twelve HD patients [59.2 ± 13.4 years, six women, BMI 26.6 ± 3.5 kg/m, 48.6 (20.1-77.2) months] on dialysis. The gut microbiota was evaluated by the 16 S ribosomal RNA gene. The mRNA expression of NLRP3 was assessed using real-time quantitative polymerase chain reaction (qPCR). Plasma levels of IL-1β were measured by ELISA. Fusobacteria and Fusobacterium negatively correlated with the mRNA expression levels of NLRP3 and IL-1β (p < 0.05). A positive correlation was observed between mRNA expression of NLRP3 and Lentisphaerae, Erysipelaloclostrium and Victivallis (p < 0.05). The relative abundances of Lentisphaerae, Spirochaetes, Abscicoccus, Colidextribacter, Desulfovibrio, Fournierella, Lawsonibacter, Ruminococcus, and Victivallis were positively correlated with IL-1β mRNA expression (p < 0.05). Regarding Archaea, IL-1β mRNA expression was positively correlated with Methanobrevibacter (p < 0.05).

CONCLUSION

In CKD patients undergoing hemodialysis, gut microbiota may be involved in NLRP3 activation and IL-1β expression, contributing to inflammation.

摘要

背景

含NOD样受体吡啉结构域3(NLRP3)炎性小体是细菌信号和代谢产物的关键传感器,可引发炎症反应。慢性肾脏病(CKD)常伴有全身炎症,这可能与肠道菌群失调有关。考虑到这种相互作用,我们旨在探讨接受血液透析(HD)的CKD患者中NLRP3炎性小体表达与肠道微生物群之间的潜在关联。

方法与结果

本研究为横断面试点研究,纳入了12例接受透析的HD患者[年龄59.2±13.4岁,女性6例,体重指数26.6±3.5kg/m²,透析时间48.6(20.1 - 77.2)个月]。通过16S核糖体RNA基因评估肠道微生物群。使用实时定量聚合酶链反应(qPCR)评估NLRP3的mRNA表达。通过酶联免疫吸附测定(ELISA)测量血浆白细胞介素-1β(IL-1β)水平。梭杆菌属和梭杆菌与NLRP3和IL-1β的mRNA表达水平呈负相关(p<0.05)。观察到NLRP3的mRNA表达与浮霉菌门、丹毒丝菌属和胜利菌属之间呈正相关(p<0.05)。浮霉菌门、螺旋体门、阿布斯球菌属、共栖杆菌属、脱硫弧菌属、福氏菌属、劳森菌属、瘤胃球菌属和胜利菌属的相对丰度与IL-1β mRNA表达呈正相关(p<0.05)。关于古菌,IL-1β mRNA表达与甲烷短杆菌呈正相关(p<0.05)。

结论

在接受血液透析的CKD患者中,肠道微生物群可能参与NLRP3激活和IL-1β表达,从而导致炎症。

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