Betaine supplementation prevents ethanol-induced disruption of intestinal tight junction integrity and liver inflammation in rats.

BACKGROUND

Alcohol-associated liver disease (ALD) remains a significant health burden. In our previous studies, we have established that chronic ethanol consumption severely impairs the hepatic methionine metabolic pathway, most harmfully by reducing the critical ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline in the SAM:SAH ratio, or methylation index, impairs essential biological methylation reactions, which is a key driver of early ALD features. Furthermore, the integrity of the gut-liver axis is crucial in ALD; ethanol damages the intestinal barrier, leading to increased translocation of bacterial endotoxins into the liver and triggering inflammation. This study investigated whether betaine, an essential methyl group donor, could prevent both the intestinal barrier disruption and subsequent liver injury caused by ethanol.

METHODS

Male Wistar rats were pair-fed Lieber-DeCarli control or ethanol diets, with or without 1 % betaine supplementation, for eight weeks. We have examined intestinal tight junction (TJ) protein localization and barrier function in the ileum. Liver injury and inflammation were assessed via serum markers (AST, endotoxin) and hepatic cytokine expression (TNFα and CCL2).

RESULTS

Ethanol feeding resulted in disorganized TJ proteins, accompanied by increased serum endotoxin and elevated markers of liver injury and inflammation (AST, cytokines). Betaine supplementation prevented these intestinal disruptions, maintained barrier function, reduced endotoxin translocation, and significantly mitigated liver inflammation and injury, despite comparable blood alcohol levels.

CONCLUSION

Betaine effectively prevents ethanol-induced intestinal barrier breakdown and subsequent liver inflammation/injury by preserving the intestinal barrier. These results suggest strong therapeutic potential for betaine in managing ALD, warranting clinical investigation.