The role and mechanism of butyrate in the prevention and treatment of diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) remains the leading cause of the end-stage renal disease and is a major burden on the healthcare system. The current understanding of the mechanisms responsible for the progression of DKD recognizes the involvement of oxidative stress, low-grade inflammation, and fibrosis. Several circulating metabolites that are the end products of the fermentation process, released by the gut microbiota, are known to be associated with systemic immune-inflammatory responses and kidney injury. This phenomenon has been recognized as the “gut–kidney axis.” Butyrate is produced predominantly by gut microbiota fermentation of dietary fiber and undigested carbohydrates. In addition to its important role as a fuel for colonic epithelial cells, butyrate has been demonstrated to ameliorate obesity, diabetes, and kidney diseases via G-protein coupled receptors (GPCRs). It also acts as an epigenetic regulator by inhibiting histone deacetylase (HDAC), up-regulation of miRNAs, or induction of the histone butyrylation and autophagy processes. This review aims to outline the existing literature on the treatment of DKD by butyrate in animal models and cell culture experiments, and to explore the protective effects of butyrate on DKD and the underlying molecular mechanism.

The gut microbiota metabolite butyrate mitigates MPTP/MPP+‐induced Parkinson's disease by inhibiting the JAK2/STAT3 signaling pathway

“…35 BU has been reported to ameliorate inflammation and oxidative stress in human diseases, including myocardial ischemia/reperfusion injury 31 and diabetic kidney disease. 36 In consistency with prior studies, BU dosedependently attenuated MPP + -induced oxidative stress in PC12 cells, as evidenced by the decreased ROS and MDA levels and the enhanced SOD and GSH levels. Besides, BU pretreatment also attenuated MPP +induced overproduction of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a concentration-dependent manner.…”

Gut microbiota and its metabolites – molecular mechanisms and management strategies in diabetic kidney disease

“…Butyrate was reported to improve the intestinal barrier function by promoting the production of colonic mucin and tight junction proteins (ZO-1) (34). It could also mitigate oxidative stress, inflammation, and fibrosis in kidney disease through GPRs or HDAC (35)(36)(37). Serum valerate and caproate levels were negatively correlated with the progression of DKD to ESRD (38).…”

The role and mechanism of the gut microbiota in the development and treatment of diabetic kidney disease

“…SCFAs, including acetate, propionate, and butyrate, are the primary end products of gut bacterial fermentation and play a key role in host colonic physiology, serving as a major source of energy for intestinal and colon cells, stimulating epithelial cell proliferation, and promoting glucose homeostasis (Cheng et al, 2022;Chi et al, 2021;Fernandes et al, 2019;Tanase et al, 2020). SCFAs mainly function through activating G-protein coupled receptors, like GPR41, GPR43, and GPR109A, and inhibiting histone deacetylase (HDAC) (Andrade-Oliveira et al, 2015;Cheng et al, 2022;Fang Q. et al, 2021;Huang et al, 2017b;Lin et al, 2022;Rooks and Garrett, 2016). In patients with DKD, the activation of GPRs by SCFAs stimulate the production of glucagon-like peptide-1 (GLP-1), improving blood glucose tolerance and insulin sensitivity (Deng L. et al, 2022;Fang Q. et al, 2021;Kim et al, 2014;Lin et al, 2022;.…”

“…In regulating intestinal inflammation, SCFAs exert antiinflammatory effects through increasing the expression of antiinflammatory cytokine interleukin-10 (IL-10) and suppressing the production of inflammatory cytokines (IL-6 and TNF-α) and the activation of nuclear factor-κB (NF-κB) (Kim et al, 2014). In addition, sodium butyrate has also been found to exert protective effects on DKD rats through activation of autophagy (Cheng et al, 2022).…”

“…On the other hand, the decrease of several beneficial SCFAs producing bacteria, especially butyrate-producing bacteria, exacerbate the pro-inflammatory environment (Lv et al, 2022;Sabatino et al, 2017;Zaky et al, 2021). Because SCFAs have shown positive effects on DKD through inhibition of inflammation and immune response (Cheng et al, 2022;Feng et al, 2018;Huang et al, 2020;Lv et al, 2022). Previous research suggested that SCFAs could protect the gut barrier from the disruption of LPS through inhibiting NLRP3 inflammasome (Feng et al, 2018).…”