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. 2022 Sep 6:13:913465.
doi: 10.3389/fmicb.2022.913465. eCollection 2022.

Mechanisms of Zhenwu decoction for the treatment of renal fibrosis at various stages: What is the role of Corynebacterium?

Lijing Du  1   2 , Yiping Zhang  1 , Shuai Ji  1   3 , Leqi Wang  1   4 , Xiaoshan Zhao  3   5 , Shikai Yan  2   4 , Xue Xiao  4 , Shasha Li  1   5
Affiliations

Mechanisms of Zhenwu decoction for the treatment of renal fibrosis at various stages: What is the role of Corynebacterium?

Lijing Du et al. Front Microbiol. .

Abstract

Many studies demonstrated that Zhenwu decoction (ZWD) is effective in the treatment of kidney fibrosis, whereas the mechanism remains unclear. In this work, a microbiomics-based strategy was used to investigate the mechanism of protective effects of ZWD on kidney fibrosis. Unilateral ureteral obstruction was used to replicate a rat model of renal fibrosis, and rats were divided into prophylactic, early, and progression stages according to the timing of administration. Feces was collected to perform microbiota evaluation by high-throughput 16S DNA sequencing. The results indicated that Corynebacterium, Alistipes, Dorea, and Lactonifactor were highlighted as key targeted flora of ZWD in the treatment of renal fibrosis, and their biological functions were related to inflammation, immunity, and renal excretion. Especially, Corynebacterium presented a significant positive correlation with the concentration of Cys-C, Scr, and BUN. The studies on the changes in inflammatory cytokines (INF-γ, IL-1β, IL-4, and TNF-α) and immunoglobulin (IgA, IgM, and IgG) confirmed the beneficial effects of ZWD on kidney fibrosis. Therefore, this study confirmed the protective effect of ZWD against renal fibrosis at various disease stages, and its mechanism was associated with re-establishing dysbiosis of the intestinal microbiota, reducing inflammation, as well as regulating immune functions. In particular, Corynebacterium may be a key flora in the treatment of renal fibrosis.

Keywords: Corynebacterium; Zhenwu decoction; inflammatory; intestinal microbiota; renal fibrosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic of the animal experiment and sampling points.
FIGURE 2
FIGURE 2
(A) Representative HE staining images of the rat left kidney in each group (magnification, × 200). (B) Pathological scoring of kidney tissue. (C) Comparison of renal parameters (Cys-C, Scr, and BUN) under different interventions. Compared with the sham operation group, *P < 0.05, ***P < 0.001; compared with the model group, #P < 0.05, ###P < 0.001.
FIGURE 3
FIGURE 3
(A) Alpha-diversity bar charts between the seven groups, including goods_coverage, Shannon, Chao1, Simpson, Ace, PD-tree, and Pielou indexes. (B) Principal coordinates analysis (PCoA). Compared with the sham operation group, *P < 0.05, **P < 0.01, ***P < 0.001; compared with the model group, #P < 0.05, ##P < 0.01.
FIGURE 4
FIGURE 4
(A) Stacked column graph representing the relative abundance of gut bacterial taxa at the phylum level in the different groups. (B) Gut microbiota differences at the genus level among each groups. (C) Spearman correlation analysis of three renal function indicators (Cys-C, Scr, and BUN) and four differential genera. Color intensity represents the magnitude of correlation; *P < 0.05, **P < 0.01, ***P < 0.001. (D) Regression analysis between Corynebacterium and three renal function indicators.
FIGURE 5
FIGURE 5
Dynamic changes of serum inflammatory cytokines and immunoglobulins before and after ZWD treatment. Compared with the sham operation group, *P < 0.05, **P < 0.01, ***P < 0.001; compared with the model group, #P < 0.05, ##P < 0.01, ###P < 0.001.
FIGURE 6
FIGURE 6
Diagram of the mechanism of action of ZWD against renal fibrosis. ↑ represents upregulation, and ↓ represents downregulation.
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