Moreover, Fu et al. (105) discovered that approximately 30% of the acetaldehyde produced in the liver was excreted into the gastrointestinal tract via the bile, where gut epithelial ALDH2 further converted it to acetate. Notably, manipulating bile flow dynamics within the liver-gut loop in the mice not only played a key role in acetaldehyde metabolism but also influenced drinking behavior. While increasing bile flow caused faster acetaldehyde clearance and higher alcohol intake, inhibiting bile acid transporters led to slower acetaldehyde clearance and reduced alcohol consumption (105). Future clinical studies should investigate the importance of enterohepatic circulation in the clearance of systemic acetaldehyde and the potential effects of drugs that affect bile flow on alcohol consumption and toxicity.
