Dynamic Changes of the Fungal Microbiome in Alcohol Use Disorder.

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

doi:10.3389/fphys.2021.699253

Abstract

BackgroundAlcohol-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.MethodsWe 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.ResultsPatients 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.ConclusionIn 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.

Highlights

Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide
Changes are observed in the intestinal mycobiome: Multiple genera and species are significantly increased in alcohol use disorder (AUD) subjects relative to control participants, including Candida, Debaryomyces, Pichia, Kluyveromyces, Issatchenkia, and C. albicans and C. zeylanoides
We show that the intestinal Candida abundance as well as the fungal serum biomarker anti-C. albicans immunoglobulin G (IgG) respond to alcohol abstinence

Summary

Introduction

Alcohol-associated liver disease (ALD) is an important cause of morbidity and mortality worldwide. Over the last few years, the contribution of the intestinal bacterial microbiome to liver disease (Hartmann et al, 2012, 2015), and more recently, the role of the fungal microbiome (mycobiome), in liver disease have been investigated (Yang et al, 2017; Bajaj et al, 2018; Chu et al, 2020; Lang et al, 2020; Lemoinne et al, 2020; Jiang et al, 2021). Alcoholic hepatitis (AH) and liver cirrhosis were associated with decreased fungal diversity and increased Candida abundance (Bajaj et al, 2018; Lang et al, 2020), whereas primary sclerosing cholangitis showed decreased contributions of Saccharomyces cerevisiae (Lemoinne et al, 2020). Studies having investigated the intestinal mycobiome in AUD patients outside the context of AH or advanced cirrhosis are lacking

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