Functional Microbiomics Reveals Alterations of the Gut Microbiome and Host Co‐Metabolism in Patients With Alcoholic Hepatitis
Abstract
Alcohol‐related liver disease is a major public health burden, and the gut microbiota is an important contributor to disease pathogenesis. The aim of the present study is to characterize functional alterations of the gut microbiota and test their performance for short‐term mortality prediction in patients with alcoholic hepatitis. We integrated shotgun metagenomics with untargeted metabolomics to investigate functional alterations of the gut microbiota and host co‐metabolism in a multicenter cohort of patients with alcoholic hepatitis. Profound changes were found in the gut microbial composition, functional metagenome, serum, and fecal metabolomes in patients with alcoholic hepatitis compared with nonalcoholic controls. We demonstrate that in comparison with single omics alone, the performance to predict 30‐day mortality was improved when combining microbial pathways with respective serum metabolites in patients with alcoholic hepatitis. The area under the receiver operating curve was higher than 0.85 for the tryptophan, isoleucine, and methionine pathways as predictors for 30‐day mortality, but achieved 0.989 for using the urea cycle pathway in combination with serum urea, with a bias‐corrected prediction error of 0.083 when using leave‐one‐out cross validation. Conclusion: Our study reveals changes in key microbial metabolic pathways associated with disease severity that predict short‐term mortality in our cohort of patients with alcoholic hepatitis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 19, 2020
- Source ID
- 10.1002/hep4.1537
Entities
People
- Bei Gao
- Benjamin Wancewicz
- Bernd Schnabl
- Bryan Roberts
- Dinesh Barupal
- Gregory Byram
- Juan G. Abraldes
- Kevin Vervier
- Lu Jiang
- Luis Valdiviez
- Oliver Fiehn
- Peter Stärkel
- Ramón Bataller
- Rohit Loomba
- Rongrong Zhou
- Shilpa Nath
- Sili Fan
- Sonja Lang
- Tong Shen
- Trevor D. Lawley
- Tsung‐chin Wu
- Xin M. Tu
- Yan Shao
- Yanhan Wang
- Yi Duan
- Ying Yng Choy
- Ying Zhang
Organizations
- UCLouvain
- University of Alberta
- University of California, Davis
- University of California, San Diego
- University of Pittsburgh
- University of Wisconsin–Madison
- Wellcome Sanger Institute