Publications

Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease

Viebahn G, Hartmann P, Lang S, Demir M, Zhang X, Fouts DE, Stärkel P, Schnabl B

PMID: 38298161

Abstract

The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera , , , and the species (), (), () were significantly increased in patients with ALD, whereas the genera and were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of , , , and to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised , , , , and . For more advanced fibrosis stages (F2-F4), the fungal signature composed of , , , and achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.