Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

对乙酰氨基酚（AP）过量引起的肝损伤是一个主要的公共卫生问题。尽管公认的AP引起的肝损伤是由于N乙酰基-对苯醌（NAPQI）的形成而引起的，NAP是一种有毒的AP代谢产物，可导致细胞损伤，但新兴证据表明，AP引起的肝损伤也与肠道菌群有关。 。然而，肠道微生物群参与的机制仍是未知之数。在我们的研究中，我们发现万古霉素（Vac）预处理（100 mg / kg，每天两次，连续4天）减轻了AP诱导的肝损伤，改变了肠道菌群的组成，并改变了血清代谢谱。此外，我们发现Vac可以提高盲肠和血清2-羟基丁酸（2-HB）的含量，从而降低AP的生物利用度并提高GSH水平，从而减轻AP诱导的小鼠细胞损伤和肝损伤。