Functional Microbial Responses to Alcohol Abstinence in Patients With Alcohol Use Disorder

Gao, Bei; Emami, Atoosa; Zhou, Rongrong; Lang, Sonja; Duan, Yi; Wang, Yanhan; Jiang, Lu; Loomba, Rohit; Brenner, David A.; Stärkel, Peter; Schnabl, Bernd

doi:10.3389/fphys.2020.00370

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…Fecal samples were collected at the time point of the admission. ( 28 ) Patients from San Diego (n = 7) were recruited in an outpatient setting. Nonalcoholic controls were enrolled in Brussels, Belgium.…”

Section: Methodsmentioning

confidence: 99%

Intestinal Virome in Patients With Alcoholic Hepatitis

et al. 2020

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BaCKgRoUND aND aIMS: Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD. appRoaCH aND ReSUltS: We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality. CoNClUSIoNS: In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.

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Section: Methodsmentioning

confidence: 99%

Intestinal Virome in Patients With Alcoholic Hepatitis

et al. 2020

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“…DNA was extracted from stool samples collected from 9 non-alcoholic controls, 41 patients with alcohol use disorder, and 81 patients with alcoholic hepatitis. DNA extraction and library preparation were performed as described previously [ 14 ]. Shotgun metagenomics sequencing was performed on Illumina HiSeq 4000 generating 150 bp paired-end reads.…”

Section: Methodsmentioning

confidence: 99%

Fungi–Bacteria Correlation in Alcoholic Hepatitis Patients

Gao

Zhang

Schnabl

2021

Toxins

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Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi were found in patients with alcohol-related liver disease. However, the functional changes of fungi and correlations between fungi and bacteria have not been investigated. In this study, we first examined the functional capacity of fungi in patients with alcohol-related liver disease using shotgun metagenomics. Among 24 MetaCyc pathways contributed by fungi, superpathway of allantoin degradation in yeast was enriched in patients with alcoholic hepatitis. Furthermore, we compared the predictive power of bacteria versus fungi and found that bacteria performed better than fungi to separate patients with alcoholic hepatitis from non-alcoholic controls and patients with alcohol use disorder. Finally, we investigated the associations between the intestinal fungi and bacteria in alcoholic hepatitis patients. Positive association between fungi and bacteria was found between Cladosporium and Gemmiger, meanwhile negative association was found between Cryptococcus and Pseudomonas in alcoholic hepatitis patients.

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“…DNA was extracted from stool samples collected from 73 patients. DNA extraction and library preparation were performed as described previously [24]. Shot-gun metagenomics sequencing was performed on an Illumina HiSeq 4000, generating 150bp paired-end reads.…”

Section: Shotgun Metagenomicsmentioning

confidence: 99%

Machine Learning Applied to Omics Datasets Predicts Mortality in Patients with Alcoholic Hepatitis

Gao

Lang

et al. 2022

Metabolites

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Alcoholic hepatitis is a major health care burden in the United States due to significant morbidity and mortality. Early identification of patients with alcoholic hepatitis at greatest risk of death is extremely important for proper treatments and interventions to be instituted. In this study, we used gradient boosting, random forest, support vector machine and logistic regression analysis of laboratory parameters, fecal bacterial microbiota, fecal mycobiota, fecal virome, serum metabolome and serum lipidome to predict mortality in patients with alcoholic hepatitis. Gradient boosting achieved the highest AUC of 0.87 for both 30-day mortality prediction using the bacteria and metabolic pathways dataset and 90-day mortality prediction using the fungi dataset, which showed better performance than the currently used model for end-stage liver disease (MELD) score.

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Functional Microbial Responses to Alcohol Abstinence in Patients With Alcohol Use Disorder

Cited by 13 publications

References 31 publications

Intestinal Virome in Patients With Alcoholic Hepatitis

Intestinal Virome in Patients With Alcoholic Hepatitis

Fungi–Bacteria Correlation in Alcoholic Hepatitis Patients

Machine Learning Applied to Omics Datasets Predicts Mortality in Patients with Alcoholic Hepatitis

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