期刊
FRONTIERS IN PHYSIOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2021.699253
关键词
fungi; mycobiome; alcohol-associated liver disease; microbiome; abstinence
类别
资金
- National Institutes of Health [K12 HD85036, R01 AA24726, R01 AA020703, U01 AA026939]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [LA 4286/1-1]
- Clinical and Translational Research Fellowship in Liver Disease by the American Association for the Study of Liver Diseases (AASLD) Foundation
- Fond National de Recherche Scientifique Belgium [J.0146.17, T.0217.18]
- Action de recherche concertee (ARC), Universite Catholique de Louvain, Belgium
- Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [BX004594]
- Biocodex Microbiota Foundation Grant
- NIH [P30 DK120515, P50 AA011999]
The study revealed dynamic changes in the intestinal fungal microbiome in patients with alcohol use disorder (AUD), and demonstrated that improved liver health after alcohol abstinence in AUD patients was associated with lower abundances of specific fungal genera and species, as well as changes in serum anti-fungal IgG levels. These findings suggest that intestinal fungi could be a potential therapeutic target to improve the outcome of patients with ALD.
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.
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