Mechanistic insights into the pleiotropic effects of butyrate as a potential therapeutic agent on NAFLD management: A systematic review

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases worldwide. As a multifaceted disease, NAFLD’s pathogenesis is not entirely understood, but recent evidence reveals that gut microbiota plays a significant role in its progression. Butyrate, a gut microbiota metabolite, has been reported to have hepato-protective effects in NAFLD animal models. The purpose of this systematic review is to determine how butyrate affects the risk factors for NAFLD. Searches were conducted using relevant keywords in electronic databases up to March 2022. According to the evidence presented in this study, butyrate contributes to a wide variety of biological processes in the gut–liver axis. Its beneficial properties include improving intestinal homeostasis and liver health as well as anti-inflammatory, metabolism regulatory and anti-oxidative effects. These effects may be attributed to butyrate’s ability to regulate gene expression as an epigenetic modulator and trigger cellular responses as a signalling molecule. However, the exact underlying mechanisms remain unclear. Human trials have not been performed on the effect of butyrate on NAFLD, so there are concerns about whether the results of animal studies can be translated to humans. This review summarises the current knowledge about the properties of butyrate, particularly its potential effects and mechanisms on liver health and NAFLD management.

Physalis alkekengi L. Calyx Extract Alleviates Glycolipid Metabolic Disturbance and Inflammation by Modulating Gut Microbiota, Fecal Metabolites, and Glycolipid Metabolism Gene Expression in Obese Mice

“…The PC supplementation partially restored the HFHF-induced decrease in SCFAs, such as butyrate and acetate contents. Butyrate can especially significantly relieve steatohepatitis by regulating the gut microbiota and intestinal barrier function, thereby reducing inflammation and oxidative damage in the liver, and it also has a good effect on blood glucose and energy balance [64].…”

Expression of PGC-1α, PPAR-α and UCP1 genes, metabolic and anthropometric factors in response to sodium butyrate supplementation in patients with obesity: A triple-blind, randomized placebo-controlled clinical trial

“…The study findings indicate that the administration of NaB resulted in a clinically significant decrease in serum concentrations of ALT and AST although it did not reach a statistically significant level. The impact of butyrate on hepatic enzymes exhibits variability throughout animal-based investigations [54]. While numerous studies have demonstrated the hepatoprotective properties of butyrate, its efficacy has been inconsistent in some investigations [54].…”

Roles of Traditional and Next-Generation Probiotics on Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review and Network Meta-Analysis

“…Firstly, it helps maintain the integrity of the intestinal barrier, reducing endotoxin entry into the bloodstream and thereby enhancing the body’s antioxidative defenses via the gut-liver axis [ 66 ]. Secondly, butyrate activates the Nrf2 pathway, promoting the expression of antioxidative enzymes and alleviating oxidative stress in liver cells [ 67 ]. Additionally, butyrate effectively inhibits oxidative DNA damage.…”