AUTHOR=Hartmann Phillipp , Lang Sonja , Zeng Suling , Duan Yi , Zhang Xinlian , Wang Yanhan , Bondareva Marina , Kruglov Andrey , Fouts Derrick E. , Stärkel Peter , Schnabl Bernd 

TITLE=Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.699253

DOI=10.3389/fphys.2021.699253

ISSN=1664-042X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>Patients with AUD had significantly increased abundance of the genera <italic>Candida</italic>, <italic>Debaryomyces</italic>, <italic>Pichia</italic>, <italic>Kluyveromyces</italic>, and <italic>Issatchenkia</italic>, and of the species <italic>Candida albicans</italic> and <italic>Candida zeylanoides</italic> 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 <italic>Candida</italic>, <italic>Malassezia</italic>, <italic>Pichia</italic>, <italic>Kluyveromyces</italic>, <italic>Issatchenkia</italic>, and the species <italic>C. albicans</italic> and <italic>C. zeylanoides</italic>. This was mirrored by significantly higher specific anti-<italic>C. albicans</italic> immunoglobulin G (IgG) and M (IgM) serum levels in AUD patients in relation to control participants, and significantly decreased anti-<italic>C. albicans</italic> IgG levels in AUD subjects after 2 weeks of abstinence. The intestinal abundance of the genus <italic>Malassezia</italic> was significantly higher in AUD subjects with progressive liver disease compared with non-progressive liver disease.</p></sec><sec><title>Conclusion</title><p>In conclusion, improved liver health in AUD patients after alcohol abstinence was associated with lower intestinal abundances of <italic>Candida</italic> and <italic>Malassezia</italic>, and lower serum anti-<italic>C. albicans</italic> IgG levels. Intestinal fungi might serve as a therapeutic target to improve the outcome of patients in ALD.</p></sec>