Roles of short-chain fatty acids in kidney diseases

Abstract

Objective: In kidney diseases, uncontrolled blood pressure, inflammation, oxidative stress, imbalanced immunity response, and metabolic dysfunction were associated with the progressive deterioration of renal function. Short-chain fatty acids (SCFAs), as a group of metabolites fermented by gut microbiota exerted regulatory effects on kidney diseases through their activation of trans-membrane G protein-coupled receptors and their inhibition of histone acetylation. In this review article, we updated recent research advances that provided an opportunity to explore our understanding in physiology and function of SCFAs in kidney disease.

Data sources: We performed a comprehensive search in both PubMed and Embase using "short-chain fatty acids" and "kidney" with no restrictions on publication date.

Study selection: After reading through the title and abstract for early screening, the full text of relevant studies was identified and reviewed to summarize the roles of SCFAs in kidney diseases.

Results: Though controversial, growing evidence suggested SCFAs appeared to have a complex but yet poorly understood communications with cellular and molecular processes that affected kidney function and responses to injury. From recent studies, SCFAs influenced multiple aspects of renal physiology including inflammation and immunity, fibrosis, blood pressure, and energy metabolism.

Conclusions: The roles of intestinal SCFAs in kidney diseases were exciting regions in recent years; however, clinical trials and animal experiments in kidney diseases were still lacked. Thus, more research would be needed to obtain better understanding of SCFAs' potential effects in kidney diseases.

Figure 1

Schematic roles of short-chain fatty acids (SCFAs) in kidney diseases. In kidney, SCFAs regulated immune responses, decreased inflammation, enhanced anti-oxidant, reduced kidney fibrosis, as well as modulated blood pressure and metabolism mainly related to their activation of G protein-coupled receptors (GPCRs) and the inhibition of histone acetylation (HDAC). All of these benefits from SCFAs improved kidney function with the decreased levels of serum creatinine and blood urea nitrogen in both acute kidney jury and chronic kidney disease. However, SCFAs also promoted acetate-induced renal disease under certain condition as the negative outcomes. IL-10: Interleukin 10; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B; ROS: Reactive oxygen species; TGF-β1: Transforming growth factor beta 1; TLR4: Toll-like receptor 4.