Yogurt alleviates alcohol-induced hepatocyte pyroptosis and inflammation via autophagy/P62/Nrf2/ROS/NLRP3 pathway

Alcohol, one of the most widely popular and consumed beverages worldwide, often leads to acute alcoholic liver injury (AALI) when excessively consumed within a short timeframe. It can further induce alcoholic hepatitis, posing a serious risk to human health and public health safety. Pyroptosis, a typical mode of programmed cell death, is closely associated with the body's inflammatory response and plays a central role in AALI. However, the role of yogurt in acute alcohol-induced pyroptosis and inflammation is unclear. In this study, we found that yogurt and its metabolite d-lactate effectively mitigate alcohol-induced liver damage in mice, reducing hepatocyte pyroptosis and attenuating the inflammatory response. For the specific mechanism, further studies have shown that yogurt may inhibit autophagy through its substance d-lactate, leading to the accumulation of P62 protein in cells. This accumulation subsequently triggers the activation of Nrf2 through nonclassical pathways. Nrf2 translocates to the nucleus to play its antioxidant role, thereby reducing intracellular reactive oxygen species levels, inhibiting the activation of the alcohol-induced NLRP3 inflammasome, and ultimately alleviating pyroptosis and inflammation. Overall, this study reveals the potential protective effect of yogurt and its metabolite d-lactate in alleviating AALI, offering new insights and scientific basis for yogurt as a dietary strategy to improve AALI.