Stachyose alleviates alcohol liver injury in mice associated with modulation of TGF-β signaling pathway and gut microbiota.

BACKGROUND

Alcoholic liver disease (ALD) is a widespread chronic disease that seriously affects physical and mental health. Stachyose (STA), a dietary supplement, has been demonstrated to be a potential active oligosaccharide for alleviating ALD, while its mechanism has not been fully revealed.

PURPOSE: This study aims to explore the effects of STA on ALD and its underlying mechanism.

METHODS

The efficacy of STA on ALD was evaluated using an ALD mouse model. The changes in the lipid profile were investigated through lipidomics. The potential mechanism was explored using transcriptomics, and the expression of key pathways was validated by Western blotting. The impact of STA on gut microbiota and SCFAs was analyzed. Finally, the fecal microbiota transplantation method was used to verify the importance of gut microbiota in the treatment of ALD with STA.

RESULTS

Our findings illustrated that STA alleviated liver injury, as evidenced by decreased levels of ALT and AST. Liver lipidomics analysis showed that STA down-regulated the levels of TG, PC, PI, PS, and DG. STA also restored the dynamic balance of the inflammatory response and oxidative stress. Mechanistically, STA treatment was predominantly associated with inhibiting the activation of the TGF-β signaling pathway in the liver. Furthermore, STA restored the intestinal homeostasis by increasing the abundance of Faecalibaculum and Muribaculum as well as decreasing the abundance of Butyricimonas, Clostridium, and Parabacteroides. Interestingly, administration of an STA-derived microbiome could also alleviate ALD.

CONCLUSION

These findings identify STA as a key bioactive ingredient capable of improving ALD, and emphasize the gut microbiota-dependent mechanism underlying its therapeutic effects.