Folic acid, as a key source of methyl donor in DNA methylation, has been proved to play a beneficial role in inflammation modulation, usually impaired in alcoholic liver disease (ALD)....

The gut–liver axis (GLA) plays an important role in the development of alcohol-induced liver injury. Alcohol consumption is typically associated with folic acid deficiency. However, no clear evidence has confirmed the effect of folic acid supplementation on alcohol-induced liver injury via GLA homeostasis. In this study, male C57BL/6J mice were given 56% (v/v) ethanol and 5.0 mg/kg folic acid daily by gavage for 10 weeks to investigate potential protective mechanisms of folic acid in alcohol-induced liver injury via GLA homeostasis. Histopathological and biochemical analyses showed that folic acid improved lipid deposition and inflammation in the liver caused by alcohol consumption and decreased the level of ALT, AST, TG, and LPS in serum. Folic acid inhibited the expression of the TLR4 signaling pathway and its downstream inflammatory mediators in the liver and upregulated the expression of ZO-1, claudin 1, and occludin in the intestine. But compared with the CON group, folic acid did not completely eliminate alcohol-induced intestine and liver injury. Furthermore, folic acid regulated alcohol-induced alterations in gut microbiota. In alcohol-exposed mice, the relative abundance of Bacteroidota was significantly increased, and the relative abundance of unclassified_Lachnospiraceae was significantly decreased. Folic acid supplementation significantly increased the relative abundance of Verrucomicrobia, Lachnospiraceae_NK4A136_group and Akkermansia, and decreased the relative abundance of Proteobacteria. The results of Spearman’s correlation analysis showed that serum parameters and hepatic inflammatory cytokines were significantly correlated with several bacteria, mainly including Bacteroidota, Firmicutes, and unclassified_Lachnospiraceae. In conclusion, folic acid could ameliorate alcohol-induced liver injury in mice via GLA homeostasis to some extent, providing a new idea and method for prevention of alcohol-induced liver injury.

NR supplementation could ameliorate high-fructose-induced lipid metabolism disorder by improving FGF21 resistance in the liver and WAT, which may be related to the inflammation state mediated by SIRT1/NF-κB signaling pathway.

Garlic oil (GO) is a kind of natural extract extracted from garlic, which has strong antioxidant activity. This study elucidates the protective mechanism of GO against alcohol‐induced high triglyceride levels. Sixty male Sprague Dawley rats were assigned to five groups, including a control group (CON), a model group (MOD) treated with alcohol 56% v/v at 8 ml kg −1 day −1 for 2 weeks then 10 ml kg −1 day −1 for 8 weeks, a low‐dose GO group (GO‐L) given GO at 20 mg kg −1 day −1 , a high‐dose GO group (GO‐H) given GO at 40 mg kg −1 day −1 , and a positive group (POS) given diammonium glycyrrhizinate at 200 mg kg −1 day −1 . The results showed that GO could significantly reduce the serum and liver triglyceride levels caused by alcohol exposure ( p < .05). The GO‐H group significantly reduced MDA level, increased SOD and GSH‐Px levels in serum, liver, and colon ( p < .05), significantly increased the levels of Sirt1 and PGC‐1α proteins and reduced FoxO1 protein level in liver ( p < .05), and significantly increased the levels of ZO‐1 and Claudin1 proteins in the colon compared to the MOD group ( p < .05). The 16S rRNA sequencing showed that the intestinal flora of the GO‐H group was significantly changed compared with the MOD group. In summary, GO has the potential to improve high triglyceride levels in serum and liver induced by alcohol exposure, which may be related to the inhibition of oxidative stress regulation of Sirt1 and its downstream proteins, and to the restoration of the intestinal barrier and intestinal flora.