Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, China.
School of Clinical Medicine, Hangzhou Medical College, Hangzhou 311399, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Mar 25;56(3):414-426. doi: 10.3724/abbs.2024021.
Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. and are elevated in the model group but significantly decreased after Ger intervention ( <0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of and , as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.
糖尿病肾病（DN）是糖尿病的严重并发症，也是终末期肾病和死亡的主要原因。倍半萜烯类化合物（如莪术烯）具有抗炎、抗氧化和抗糖尿病肾病作用。然而，尚不清楚莪术烯改善糖尿病肾病小鼠肾脏损伤是否与肠道微生物菌群的异常组成和代谢物有关。本研究通过 16S rRNA 测序和非靶向粪便代谢组学生成了糖尿病肾病小鼠模型，以探讨莪术烯对肾功能的潜在治疗作用和机制。尽管微生物多样性没有显著变化，但 DN 组的肠道微生物菌群结构有很大差异。与健康对照组相比，DN 组的 和 显著升高，而经莪术烯干预后则显著降低（ <0.05）。在莪术烯治疗下，肠道微生物菌群的多样性和丰富度没有显著差异。肠道菌群失衡导致代谢物失调，非靶向代谢组学数据表明，DN 组中硬脂酸表达水平较高，而油酸可能是莪术烯在 DN 模型中发挥治疗作用的潜在标志物。总的来说，莪术烯改善了糖尿病小鼠的肾脏损伤，部分原因可能是通过减少 和 的丰度，以及调节相关代谢物（如油酸、石胆酸）的增加和硬脂酸的减少。本研究扩展了对莪术烯治疗糖尿病肾病时肠道微生物菌群和代谢物之间关系的认识，为利用天然产物通过调节肠道微生物菌群来治疗糖尿病肾病提供了理论依据。
