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Gut Microbiota Modulation by Abelmoschus manihot (L.) Improves Circulating Metabolites and Alleviates Diabetic
Qing Xu1, Yuhui Song1, Hongmei Yu1
1Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, China, cpu.edu.cn.
Background:
Huangkui capsule (HKC), derived from the ethanol extract of Abelmoschus manihot (L.) flowers, is widely used in China for treating kidney diseases, including diabetic nephropathy (DN). Our previous study demonstrated that HKC modulates the intestinal microbiota and circulating metabolites in non-obese diabetic mice, a type 1 diabetes model. To further explore its efficacy, we evaluated HKC in db/db mice, a well-established type 2 diabetes and DN model.
Methods:
An HKC cohort studied in 2022 was compared with historical Ctrl and DN cohorts studied in 2021. Shotgun metagenomic sequencing was performed to characterize intestinal microbiota changes, while liquid chromatography-mass spectrometry (LC-MS)-based plasma metabolomics was used to identify alterations in circulating metabolites. The biological functions of the altered microbiota and plasma metabolites were analyzed, and the potential association between the intestinal microbiome and plasma metabolome was evaluated.
Results:
Compared with the historical DN cohort, the HKC cohort had higher abundances of Streptococcaceae, Streptococcus, and Massilimaliae and lower abundances of Alloprevotella and Prevotellamassilia in exploratory comparisons. In the HKC-versus-DN comparison, the archived gene set enrichment analysis reported 15 pathways with nominal positive enrichment. Additionally, 12 plasma metabolites were upregulated and 14 downregulated, including branched-chain amino acids (DL-leucine, DL-valine, D-isoleucine), organic acids (N-methyl-α-aminoisobutyric acid, guanidineacetic acid), and choline.
Conclusion:
In db/db mice, the cohort receiving A. manihot (L.)-derived HKC had lower urinary albumin-to-creatinine ratio (UACR) and different intestinal microbiota and plasma metabolite profiles than the historical DN cohort, highlighting its therapeutic potential for DN.