QiDiTangShen granules modulated the gut microbiome composition and improved bile acid profiles in a mouse model of diabetic nephropathy

Biomed Pharmacother. 2021 Jan:133:111061. doi: 10.1016/j.biopha.2020.111061. Epub 2020 Nov 28.

Abstract

QiDiTangShen granules (QDTS), a traditional Chinese herbal medicine, have been used in clinical practice for treating diabetic kidney disease for several years. In our previous study, we have demonstrated that QDTS displayed good efficacy on reducing proteinuria in mice with diabetic nephropathy (DN). However, the exact mechanism by which QDTS exerts its reno-protection remains largely unknown. To ascertain whether QDTS could target the gut microbiota-bile acid axis, the db/db mice were adopted as a mouse model of DN. After a 12-week of treatment, we found that QDTS significantly reduced urinary albumin excretion (UAE), and attenuated the pathological injuries of kidney in the db/db mice, while the body weight and blood glucose levels of those mice were not affected. In addition, we found that QDTS significantly altered the gut microbiota composition, and decreased serum levels of total bile acid (TBA) and BA profiles such as β-muricholic acid (β-MCA), taurocholic acid (TCA), tauro β-muricholic acid (Tβ-MCA) and deoxycholic acid (DCA). These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. However, there was no significant difference between QDTS-treated and -untreated db/db mice regarding the renal expression of FXR, indicating that other mechanisms may be involved. Conclusively, our study revealed that QDTS significantly alleviated renal injuries in mice with DN. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in DN, but the specific mechanism merits further study.

Keywords: Bile acids; Diabetic nephropathy; Gut Microbiota; QiDiTangShen granules.

MeSH terms

  • Animals
  • Bile Acids and Salts / blood*
  • Biomarkers / blood
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / microbiology
  • Diabetic Nephropathies / pathology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Dysbiosis
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Intestines / drug effects*
  • Intestines / microbiology
  • Intestines / pathology
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / ultrastructure
  • Male
  • Proteinuria / blood
  • Proteinuria / microbiology
  • Proteinuria / prevention & control

Substances

  • Bile Acids and Salts
  • Biomarkers
  • Drugs, Chinese Herbal
  • QiDiTangShen granules