Schematic representation of the mechanisms of QiDiTangShen granules (QDTS) in attenuating diabetic nephropathy. QDTS treatment modulated gut microbiota (GM) that was associated with BA metabolism, and reversed the increase in the serum levels of BA profiles, thereby ameliorating DN. However, QDTS treatment had no significant effect on the renal expression of FXR, other mechanisms may be involved in the renal protection of QDTS via the gut microbiota-BA axis. β-MCA, β-muricholic acid; ; TβMCA, tauro β-muricholic acid; TCA, taurocholic acid; DCA, deoxycholic acid; TBA, total bile acid; FXR, FXR; DN, diabetic nephropathy.

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.