Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhengzhou University, Zhengzhou, China.
Front Endocrinol (Lausanne). 2022 Dec 19;13:964389. doi: 10.3389/fendo.2022.964389. eCollection 2022.
Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation.
A total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome-microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective.
The diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid).
The fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes influencing pathogens' effect on DKD mice's metabolism.
糖尿病肾病（DKD）是糖尿病（DM）最常见的并发症之一，与肠道微生物失调有关。我们旨在建立一个诊断模型，以辅助临床实践并发现对 DKD 发病机制和恶化有重要贡献的关键有害微生物群落。
共招募了来自郑州大学第一附属医院的 180 名 DKD 患者和 348 名非 DKD 人群（138 名 DM 和 210 名健康志愿者）的 528 份粪便样本，并将其随机分为发现阶段和验证阶段。使用 16S rRNA 测序比较肠道微生物组成。然后，根据临床阶段将 180 名 DKD 患者分为四组，并进行肠道微生物分析。我们建立了 DKD 小鼠模型和健康粪便微生物移植（FMT）模型，以验证肠道微生物对 DKD 的影响并选择潜在的有害微生物群落。对小鼠模型进行非靶向代谢组-微生物组联合分析有助于从代谢角度破译发病机制。
与非 DKD 人群相比，DKD 患者的肠道微生物多样性显著降低，而在 DKD 阶段更严重的患者中则增加。健康肠道微生物重建后，小鼠的 DKD 严重程度得到缓解。在 DKD 表型更严重的患者（即 DKD 和 DKD5 患者和 DKD 小鼠）中，常见的有害微生物群落积累。有害微生物群落与血清损伤代谢物（如胆酸和马尿酸）呈正相关。
DKD 患者的粪便微生物群落发生了明显改变。通过对人类和动物模型的粪便分析，选择了积累的有害病原体。部分恢复健康的肠道微生物群可以缓解 DKD 表型，影响病原体对 DKD 小鼠代谢的作用。
