Wolfberry prevented liver damage caused by anti-tuberculosis drugs associated with the YAP1/FXR pathway through gut microbiota.

Background: The prevalence of anti-tuberculosis drug-induced liver injury (AT-DILI) is significant, with severe cases potentially leading to liver failure or mortality. Research indicates that first-line anti-tuberculosis drugs (ATDs), including rifampicin (RIF) and isoniazid (INH), cause a lasting disruption of gut flora, which is significantly associated with drug-induced toxicity. Wolfberry ( Methods: Forty male Kunming (KM)mice were randomly allocated into four groups: normal, model, wolfberry and Polyenylphosphatidylcholine (PPC) group ( Results: Results showed AT-DILI decreased beneficial gut microbiota abundance and increased CYP7A1 expression associated with the YAP1/FXR pathway. Wolfberry intervention enriched beneficial microbiota, increased goblet cells, upregulated tight junction protein ZO-1, and enhanced intestinal barrier function, while reducing serum ALT, AST, and TBA. Additionally, wolfberry increased nuclear YAP1 expression, activated FXR, and downregulated CYP7A1 to reduce TBA synthesis. The key finding is that after antibiotics clear the gut microbiota, wolfberry failed to activate the YAP1/FXR pathway. Conclusion: Wolfberry comprehensively prevented liver damage under the condition of gut microbiota presence by enhancing gut microbiota diversity, strengthening intestinal barrier function, associating with the YAP1/FXR pathway.