Microbiome as a potential diagnostic and predictive biomarker in severe alcoholic hepatitis

Soon Sun Kim; Jung Woo Eun; Hyo Jung Cho; Do Seon Song; Chang Wook Kim; Young Seok Kim; Sung Won Lee; Yoon-Keun Kim; Jinho Yang; Jinhee Choi; Hyung Joon Yim; Jae Youn Cheong

doi:10.1111/apt.16200

Microbiome as a potential diagnostic and predictive biomarker in severe alcoholic hepatitis

Aliment Pharmacol Ther. 2021 Feb;53(4):540-551. doi: 10.1111/apt.16200. Epub 2020 Dec 2.

Authors

Affiliations

¹ Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea.
² Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea.
³ Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, South Korea.
⁴ Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea.
⁵ Department of Internal Medicine, Bucheon St. Mary's Hospital College of Medicine, The Catholic University of Korea, Bucheon, South Korea.
⁶ Institute of MD Healthcare Inc., Seoul, South Korea.
⁷ Department of Internal Medicine, Korea University Ansan Hospital, Ansan, South Korea.

PMID: 33264437
DOI: 10.1111/apt.16200

Abstract

Background: Severe alcoholic hepatitis (AH) is the most aggressive form of alcohol-related liver disease with high mortality. The microbiome is an emerging therapeutic target in alcohol-related liver disease.

Aims: To investigate the microbiome composition in patients with severe AH, and to determine microbiome recovery after rifaximin treatment in gut bacteria and bacteria derived-extracellular vesicles.

Methods: We enrolled 24 patients with severe AH and 24 healthy controls. Additional faecal samples were collected after 4 weeks in 8 patients with severe AH who completed rifaximin treatment. Treatment response was defined based on Lille score model after 7 days of treatment. Metagenomic profiling was performed using 16S ribosomal RNA amplicon sequencing.

Results: Faecal microbiomes of patients with severe AH had lower alpha diversity and higher beta diversity than those of healthy controls in both gut bacteria and extracellular vesicles. Bacilli, Lactobacillales and Veillonella were significantly increased in the gut bacteria of patients with severe AH, and Veillonella, Veillonella parvula group and Lactobacillales were significantly increased in the extracellular vesicles of patients with severe AH. Eubacterium_g23, Oscillibacter and Clostridiales decreased in the gut bacteria of patients with severe AH, and Eubacterium_g23, Oscillibacter and Christensenellaceae decreased in the extracellular vesicles of patients with severe AH. After rifaximin treatment, 17 taxa in the gut bacteria and 23 taxa in extracellular vesicles were significantly restored in patients with severe AH. In common, Veillonella and Veillonella parvula group increased in patients with severe AH and decreased after rifaximin treatment, and Prevotella and Prevotellaceae decreased in patients with severe AH and increased after rifaximin treatment. Treatment non-responders showed a significantly lower abundance of Prevotella at baseline than did treatment responders.

Conclusion: Dysbiosis was confirmed in severe AH but was alleviated by rifaximin treatment. Taxa associated with severe AH can be candidate biomarkers or therapeutic targets.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Dysbiosis
Gastrointestinal Microbiome*
Hepatitis, Alcoholic* / diagnosis
Hepatitis, Alcoholic* / drug therapy
Humans
Microbiota*
Veillonella

Substances

Biomarkers

Supplementary concepts

Veillonella parvula