Improved bile acid profiles of diabetic nephropathy

We are very pleased to share the giabetic nephropathy study published in Biomedicine & Pharmacotherapy Journal. The authors of “QiDiTangShen granules modulated the gut microbiome composition and improved bile acid (BA) profiles in a mouse model of diabetic nephropathy utilized Metware’s proprietary Bile acid targeted metabolism detection and reported 50+ bile acids. This study aimed at exploring whether the gut microbiota-bile acid axis was implicated in the mechanism by which the QiDiTangShen (QDTS) medicine ameliorated diabetic nephropathy (DN).



Understanding the Microbiome's Role in Diabetic Nephropathy

Diabetes mellitus is one of the major causes of chronic kidney disease worldwide, and about 20–40 % of patients with diabetes will develop diabetic kidney disease. Increasing evidence suggests that dysregulation of the gut microbiota (GM) is involved in diabetes and several kidney diseases. GM dysbiosis may cause systemic inflammation by increasing the intestinal permeability, and renal injuries by its derived uremic toxins, such as indoxyl sulphate and p-cresyl sulphate, leading to the inflammatory cytokines release and reactive oxygen species production. Microbial-produced metabolites such as BA are also implicated in acute kidney injury and chronic kidney disease. Activation of BA receptors has promising therapeutic potential in the prevention of diabetic nephropathy.


QiDiTangShen and its Impact on Bile Acid and Lipid Metabolism

QiDiTangShen-herbal-medicineQiDiTangShen granules, as a traditional Chinese herbal medicine composed of seven herbs, including rehmannia glutinosa, astragalus propinquus, euryaleferox, cornus officinalis, whitmania pigra, rheum officinale and hedyotis diffusa, have been widely used in clinical practice for treating diabetic kidney disease. In this study, QDTS infusion to the db/db mice (a mouse model of diabetic nephropathy) reduced proteinuria and ameliorated renal pathological changes. Treatment with QDTS and valsartan, however, had no significant impact on the levels of body weight and flasing blood glucose.


Gut Microbiome Modulation and Serum Bile Acid Profiles: A Metabolomics Perspective

Further 16S rRNA gene sequencing analysis revealed signiciant alterations of the gut microbiota compositions. Compared with mice in the control group (C), mice in the db/db mice group (DM) were enriched in Lactobacillus, Bacteroides, Lachnospiraceae_NK4A136 group, Rikenellaceae_RC9_gut group, Alistipes and Eubacterium_xylanophilum group. QDTS infusion to the healthy mice (CQD) and the db/db mice (DMQD) prevented the increase in abundance of Lactobacillus, Bacteroides and Lachnospiraceae_NK4A136 group. 



QDTS treatment modulated the gut microbiota in db/db mice


Metabolic profiling analysis of serum BAs was performed to determine whether the microbial alterations induced by QDTS would impact BA profiles. Compared with mice in the control group, the DM group showed significantly higher levels of taurocholic acid (TCA) and tauro β-muricholic acid (Tβ-MCA). By contrast, treatment with QDTS markedly decreased the levels of β-muricholic acid (β-MCA), deoxycholic acid (DCA), TCA and Tβ-MCA in db/db mice (DMQD). Overall, the QDTS intervention substantially reduced the levels of total BAs. These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. Among which, TβMCA is the most potent agonistic natural ligand for FXR, while DCA, CA and their taurine-conjugated forms are agonists of FXR. Further analysis revealed significant correlation between serum BA profiles and the relative abundance of most genera detected. In particular, TβMCA and TCA were positively associated with the relative abundance of Lachnospiraceae_NK4A136_group and Bacteroides, whereas the ratio of FXR agonistic to antagonistic BAs was negatively associated with the abundance of Lachnospiraceae_NK4A136_group.



Serum bile acid profiles


Conclusively, the authors revealed QDTS significantly alleviated renal injuries in mice with diabetic nephropathy by decreasing serum levels of total bile acid and BA profile through altering the gut microbiota composition. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in diabetic nephropathy.


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