Yi-Shen-Hua-Shi granule protects against proteinuria associated with modulating flora microbiota in patients with chronic kidney disease

Aim: Gut microbiota dysbiosis is prevalent in patients with chronic kidney disease (CKD). This single-center randomized controlled trial aimed to explore whether the Chinese medcine, Yi-Shen-Hua-Shi (YSHS) granule, could modulate gut microbiota to ameliorate proteinuria. Materials and Methods: 120 patients were enrolled according to our criteria, and then randomized to receive renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (N=56) or RAAS inhibitor (N=47) alone for 4 months, and finally 103 patients completed the study. We collected baseline and follow-up fecal samples and tracked clinical outcomes from the participants. Total bacterial DNA was extracted, and fecal microbiome was analyzed using bioinformatics. Results: Baseline serum creatinine and decrease of 24-hour proteinuria significantly differed between the intervention and control group. There was no significant difference among gut microbiota diversity between the two groups. After 4-month of YSHS intervention, the relative abundance of bacteria based on genus level that have beneficial effects on the body such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium and Sutterella significantly increased, while the pathogenic bacteria that may be harmful to the body such as Eggerthella and Clostridium innocuum group decreased. But we could not find these changes in the control group. The redundancy analysis showed decline of 24-hour proteinuria during follow-up significantly affected the gut microbiome in the YSHS group, which was negatively correlated with various bacteria taxa, such as Lachnospiraceae and Lachnoclostridium genus. KEGG analysis also showed the role of YSHS to regulate glycan, lipid, and vitamins metabolism. Conclusions: Our findings indicated that YSHS granule to reduce proteinuria associated with mitigating dysbiosis of gut microbiota in CKD patients. The definite mechanisms of YSHS to improve proteinuria should be explored further.