The signatures and crosstalk of gut mycobiome, microbiome, and metabolites in drug-induced liver injury

Drug-induced liver injury (DILI) is a significant adverse drug reaction with a rising incidence, yet it lacks specific non-invasive biomarkers for diagnosis and severity stratification. While gut bacterial dysbiosis has been implicated in DILI, the role of gut fungal flora remains largely unexplored. In this study, fecal samples from 27 patients with traditional Chinese medicine (TCM)-associated DILI and 30 healthy controls (HC) underwent microbial sequencing and serum metabolite detection. We identified significant gut fungal dysbiosis in patients, characterized by an enrichment of Candida and Aspergillus and a depletion of Saccharomyces and Cutaneotrichosporon. Key species like Cutaneotrichosporon curvatum and Aspergillus jensenii exhibited high diagnostic accuracy (AUC > 0.9). Integrating top fungal, bacterial (e.g. Lactobacillus gasseri), and metabolic (e.g. Monocrotaline) biomarkers into combined models achieved superior performance for diagnosing TCM-associated DILI (AUC = 0.9955) and for stratifying disease severity (AUC = 0.9909). In conclusion, gut fungal signatures serve as sensitive and specific non-invasive biomarkers for TCM-associated DILI. Their integration with bacterial and metabolic data further enhances diagnostic precision, offering new avenues for early intervention and personalized management of DILI.