Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder
Phillipp Hartmann, Sonja Lang, Su-Ling Zeng, Yi Duan, Xinlian Zhang, Yanhan Wang, Marina Bondareva, Andrey Kruglov, Derrick E. Fouts, Peter Stärkel, Bernd Schnabl
Abstract
Background Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of ALD; however, little is known about commensal fungi therein. Methods We studied the dynamic changes of the intestinal fungal microbiome, or mycobiome, in 66 patients with alcohol use disorder (AUD) and after 2 weeks of alcohol abstinence using internal transcribed spacer 2 (ITS2) amplicon sequencing of fecal samples. Results Patients with AUD had significantly increased abundance of the genera Candida , Debaryomyces , Pichia , Kluyveromyces , and Issatchenkia , and of the species Candida albicans and Candida zeylanoides compared with control subjects. Significantly improved liver health markers caspase-cleaved and intact cytokeratin 18 (CK18-M65) levels and controlled attenuation parameter (CAP) in AUD patients after 2 weeks of alcohol abstinence were associated with significantly lower abundance of the genera Candida , Malassezia , Pichia , Kluyveromyces , Issatchenkia , and the species C. albicans and C. zeylanoides . This was mirrored by significantly higher specific anti- C. albicans immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti- C. albicans IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus Malassezia was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease. Conclusion In conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of Candida and Malassezia , and lower serum anti- C. albicans IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.