Wu Mengqi, Zhou Xin, Chen Saiping, Wang Yuqing, Lu Bin, Zhang Aiping, Zhu Yanqin, Huang Min, Wang Jiarui, Liu Junyi, Zhu Fenggui, Liu Hong, Lin Riyang
Department of Nephrology, Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of General Medicine, Tianshui Wulin Street Community Heal Care Centre, Hangzhou, Zhejiang, China.
Front Cell Infect Microbiol. 2025 Jun 27;15:1606700. doi: 10.3389/fcimb.2025.1606700. eCollection 2025.
Diabetic kidney disease (DKD) exhibits heterogeneous progression, implicating factors beyond hyperglycemia, such as gut microbiota dysbiosis. However, microbial distinctions among biopsy-confirmed pure DKD, DKD with non-diabetic renal disease (DKD+NDRD), and long-term diabetes without nephropathy (DM) remain unclear. This study aimed to identify gut microbial and functional biomarkers differentiating these groups.
We enrolled 40 biopsy-confirmed participants classified into DKD (n=26), DM (n=8), and DKD+NDRD (n=6) groups. Gut microbiota was profiled using 16S rRNA sequencing. Microbial diversity, composition, and functional prediction (PICRUSt2 analysis) were compared among groups. Biomarkers were identified using LEfSe analysis.
No significant differences in alpha-diversity (Chao1, Shannon indices) or beta-diversity (PCoA/PCA) were observed among groups. Taxonomic analysis revealed distinct microbial signatures: DKD patients showed enrichment of Olsenella and reduced Faecalibacterium prausnitzii (a short-chain fatty acid producer), while DM patients exhibited higher Roseburia and Flavonifractor. The DKD+NDRD group was uniquely enriched in Prevotella_9. Functional prediction highlighted elevated pyruvate metabolism and bacterial toxin pathways in DKD, contrasting with enhanced linoleic acid metabolism in DM and attenuated endotoxin-related pathways in DKD+NDRD.
This study delineates gut microbiota profiles and functional shifts across DKD, DM, and DKD+NDRD. Key taxa (Olsenella, Prevotella_9) and metabolic pathways (pyruvate, toxin production) may serve as biomarkers for DKD progression and differential diagnosis. The findings underscore the gut-kidney axis's role in DKD pathogenesis and suggest microbiota-targeted interventions for precision management. Further validation in larger cohorts is warranted.
糖尿病肾病（DKD）呈现出异质性进展，这意味着除高血糖外还有其他因素参与其中，比如肠道微生物群失调。然而，经活检确诊的单纯DKD、合并非糖尿病性肾病的DKD（DKD+NDRD）以及无肾病的长期糖尿病患者（DM）之间的微生物差异仍不明确。本研究旨在识别区分这些组别的肠道微生物和功能生物标志物。
我们纳入了40名经活检确诊的参与者，分为DKD组（n=26）、DM组（n=8）和DKD+NDRD组（n=6）。使用16S rRNA测序对肠道微生物群进行分析。比较各组之间微生物的多样性、组成和功能预测（PICRUSt2分析）。使用LEfSe分析确定生物标志物。
各组之间在α多样性（Chao1、香农指数）或β多样性（主坐标分析/主成分分析）方面未观察到显著差异。分类学分析揭示了不同的微生物特征：DKD患者表现出奥尔森氏菌属富集，而普拉梭菌（一种短链脂肪酸产生菌）减少，而DM患者则表现出较高的罗氏菌属和黄酮分解菌属。DKD+NDRD组独特地富集了普雷沃氏菌属9。功能预测突出了DKD中丙酮酸代谢和细菌毒素途径的升高，与DM中增强的亚油酸代谢以及DKD+NDRD中减弱的内毒素相关途径形成对比。
本研究描绘了DKD、DM和DKD+NDRD患者的肠道微生物群特征和功能变化。关键分类群（奥尔森氏菌属、普雷沃氏菌属9）和代谢途径（丙酮酸、毒素产生）可能作为DKD进展和鉴别诊断的生物标志物。这些发现强调了肠-肾轴在DKD发病机制中的作用，并提示针对微生物群的干预措施以实现精准管理。有必要在更大的队列中进行进一步验证。
