Nicolas Trainel

Acute oral exposure to ChCl : urea DES induces gut microbiota dysbiosis, disrupts the bile acid-FXR-liver axis, and triggers subclinical hepatic inflammation, revealing critical toxicological endpoints overlooked by classical safety markers.

Background: Gut mycobiome alterations have been reported in alcohol-associated liver disease (ALD). However, fungal signals may reflect both external exposure and disease-associated ecological alterations. We aimed to characterize community-level restructuring of the gut mycobiome using ecological annotation based on food association, and to assess its relationship with fungal host exposure, disease severity, and clinical outcomes.Methods: We analyzed fungal-specific internal transcribed spacer 2 (ITS2) amplicon sequencing data from the feces of 110 patients with ALD and 28 healthy controls. To capture in vivo dynamics, we performed fecal microbiota transplantation (FMT) from patients with ALD into mice followed by alcohol administration (Lieber–DeCarli diet).Findings: Compared with healthy controls, Malassezia sp. and non-albicans Candida showed significantly higher relative abundances in ALD, yet their association with disease severity remained inconsistent. The imbalance between non-food-associated and food-associated fungi, quantified as set-level log-ratio, increased alongside disease severity and was positively correlated with total bilirubin. This progressive compositional shift was replicated in an independent ALD cohort. Of two circulating markers of fungal exposure, 1,3-β-D-glucan correlated with the set-level log-ratio while Anti–Saccharomyces cerevisiae antibodies (ASCA) were associated with worse transplant-free survival. In the translational mouse model, FMT reshaped the intestinal mycobiome. Donor-derived fungi exhibited unstable engraftment, yielding higher donor-dependent configuration of newly emerged fungi rather than individual taxa transfers.Interpretation: Gut mycobiome dysbiosis in ALD is characterized by a progressive shift in the balance between food- and non-food-associated taxa rather than by enrichment of individual fungi. This shift was accompanied by greater systemic fungal antigen exposure, but only cumulative exposure was associated with long-term survival. These findings underscore the critical necessity of accounting for ecological origins to unlock the translational interpretability of mycobiome datasets.