State key laboratory of bioactive substances and functions of natural medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, Beijing, 100050, China.
Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Commun Biol. 2023 Nov 22;6(1):1189. doi: 10.1038/s42003-023-05581-9.
Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.
从绣球花（HP）中分离出的香豆素在实验性膜性肾炎（MN）中具有肾脏保护作用，但作用机制尚不清楚。目前，我们研究 HP 对肠道菌群失调的调节是否有助于其肾脏保护作用。用 HP 治疗实验性 MN 大鼠 6 周。进行粪便 16S rDNA 测序和代谢组学分析。进行粪便微生物群移植（FMT）评估研究。结果表明，MN 大鼠存在肾功能恶化和肠道菌群失调，表现为厚壁菌门/拟杆菌门比值升高，多样性和丰富度降低，但 HP 治疗可逆转这些变化。肠道菌群失调的减少与 HP 治疗大鼠结肠完整性的改善和内毒素血症的降低有关。HP 通过增加短链脂肪酸的产生和抑制尿毒症毒素前体的产生，使粪便代谢物的异常水平恢复正常。将 HP 治疗后的粪便进行 FMT 移植到 MN 动物中，可适度降低内毒素血症和蛋白尿。此外，HP 中的主要香豆素仅被肠道微生物群生物转化为更具生物活性的 7-羟基香豆素，从而增强了 HP 在体内的作用。肠道微生物群的耗竭部分消除了其肾脏保护作用。总之，HP 与肠道微生物群的双向相互作用有助于其有益作用。
