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肠道微生物群工程预防糖尿病肾病:一项干预研究。

Gut Microbiome Engineering for Diabetic Kidney Disease Prevention: A Intervention Study.

作者信息

Qumsani Alaa Talal

机构信息

Biology Department, Al-Jumum University College, Umm Al-Qura University, Makkah 24382, Saudi Arabia.

出版信息

Biology (Basel). 2025 Jun 19;14(6):723. doi: 10.3390/biology14060723.

DOI:10.3390/biology14060723
PMID:40563973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12189892/
Abstract

The gut microbiota has emerged as a critical modulator in metabolic diseases, with substantial evidence supporting its role in attenuating diabetes-related nephropathy. Recent investigations demonstrate that strategic manipulation of intestinal microflora offers novel therapeutic avenues for safeguarding renal function against diabetic complications. This investigation sought to determine the nephroprotective potential of () administration in diabetic nephropathy models. Six experimental cohorts were evaluated: control, probiotic-supplemented control, diabetic, diabetic receiving probiotic therapy, diabetic with antibiotics, and diabetic treated with both antibiotics and probiotics. Diabetic conditions were established via intraperitoneal administration of streptozotocin (50 mg/kg) following overnight fasting, according to validated protocols for experimental diabetes induction. Probiotic therapy (3 × 10 CFU/kg, bi-daily) began one month before diabetes induction and continued throughout the study duration. Glycemic indices were monitored at bi-weekly intervals, inflammatory biomarkers, renal function indices, and urinary albumin excretion. The metabolic profile was evaluated through the determination of HOMA-IR and the computation of metabolic syndrome scores. Microbiome characterization employed 16S rRNA gene sequencing alongside metagenomic shotgun sequencing for comprehensive microbial community mapping. supplementation substantially augmented microbiome richness and evenness metrics. Principal component analysis revealed distinct clustering of microbial populations between treatment groups. The / ratio, an emerging marker of metabolic dysfunction, normalized following probiotic intervention in diabetic subjects. : administration markedly attenuated diabetic progression, achieving glycated hemoglobin reduction of 32% compared to untreated controls. Pro-inflammatory cytokine levels (IL-6, TNF-α) decreased significantly, while anti-inflammatory mediators (IL-10, TGF-β) exhibited enhanced expression. The renal morphometric analysis demonstrated preservation of glomerular architecture and reduced interstitial fibrosis. Additionally, transmission electron microscopy confirmed the maintenance of podocyte foot process integrity in probiotic-treated groups. : The administration of demonstrated profound renoprotective efficacy through multifaceted mechanisms, including microbiome reconstitution, metabolic amelioration, and inflammation modulation. Therapeutic effects suggest the potential of a combined probiotic and pharmacological approach to attenuate diabetic-induced renal pathology with enhanced efficacy.

摘要

肠道微生物群已成为代谢性疾病的关键调节因子,有大量证据支持其在减轻糖尿病相关肾病中的作用。最近的研究表明,对肠道微生物群进行策略性调控为保护肾功能免受糖尿病并发症影响提供了新的治疗途径。本研究旨在确定()给药在糖尿病肾病模型中的肾保护潜力。评估了六个实验队列:对照组、补充益生菌的对照组、糖尿病组、接受益生菌治疗的糖尿病组、使用抗生素的糖尿病组以及同时使用抗生素和益生菌治疗的糖尿病组。根据经过验证的实验性糖尿病诱导方案,在禁食过夜后通过腹腔注射链脲佐菌素(50 mg/kg)建立糖尿病状态。益生菌治疗(3×10 CFU/kg,每日两次)在糖尿病诱导前一个月开始,并持续整个研究期间。每两周监测一次血糖指数、炎症生物标志物、肾功能指标和尿白蛋白排泄。通过测定HOMA-IR和计算代谢综合征评分来评估代谢状况。微生物组特征分析采用16S rRNA基因测序以及宏基因组鸟枪法测序进行全面的微生物群落图谱绘制。()补充显著提高了微生物组丰富度和均匀度指标。主成分分析显示治疗组之间微生物种群有明显聚类。/比值是代谢功能障碍的一个新兴标志物,在糖尿病受试者接受益生菌干预后恢复正常。:()给药显著减轻了糖尿病进展,与未治疗的对照组相比,糖化血红蛋白降低了32%。促炎细胞因子水平(IL-6、TNF-α)显著降低,而抗炎介质(IL-10、TGF-β)表达增强。肾脏形态计量学分析表明肾小球结构得以保留,间质纤维化减少。此外,透射电子显微镜证实益生菌治疗组足细胞足突完整性得以维持。:()给药通过多方面机制展现出显著的肾脏保护功效,包括微生物组重建、代谢改善和炎症调节。治疗效果表明联合益生菌和药物治疗方法有可能以更高的疗效减轻糖尿病引起的肾脏病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/4c0d11b2fe61/biology-14-00723-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/9b3fca53442a/biology-14-00723-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/4c0d11b2fe61/biology-14-00723-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/9b3fca53442a/biology-14-00723-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/82dfb342b464/biology-14-00723-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/52390bd031b9/biology-14-00723-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/08b225b28ff7/biology-14-00723-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c916/12189892/4c0d11b2fe61/biology-14-00723-g005.jpg

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