The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Puri P, Liangpunsakul S, Christensen JE, Shah VH, Kamath PS, Gores GJ, Walker S, Comerford M, Katz B, Borst A, Yu Q, Kumar DP, Mirshahi F, Radaeva S, Chalasani NP, Crabb DW, Sanyal AJ
Journal
Hepatology (Baltimore, Md.)
Year
2018
Intestinal dysbiosis is implicated in alcoholic hepatitis (AH). However, changes in the circulating microbiome, its association with the presence and severity of AH, and its functional relevance in AH is unknown. Qualitative and quantitative assessment of changes in the circulating microbiome were performed by sequencing bacterial DNA in subjects with moderate AH (MAH) (n = 18) or severe AH (SAH) (n = 19). These data were compared with heavy drinking controls (HDCs) without obvious liver disease (n = 19) and non-alcohol-consuming controls (NACs, n = 20). The data were related to endotoxin levels and markers of monocyte activation. Linear discriminant analysis effect size (LEfSe) analysis, inferred metagenomics, and predictive functional analysis using PICRUSt were performed. There was a significant increase in 16S copies/ng DNA both in MAH (P < 0.01) and SAH (P < 0.001) subjects. Compared with NACs, the relative abundance of phylum Bacteroidetes was significantly decreased in HDCs, MAH, and SAH (P < 0.001). In contrast, all alcohol-consuming groups had enrichment with Fusobacteria; this was greatest for HDCs and decreased progressively in MAH and SAH. Subjects with SAH had significantly higher endotoxemia (P = 0.01). Compared with alcohol-consuming groups, predictive functional metagenomics indicated an enrichment of bacteria with genes related to methanogenesis and denitrification. Furthermore, both HDCs and SAH showed activation of a type III secretion system that has been linked to gram-negative bacterial virulence. Metagenomics in SAH versus NACs predicted increased isoprenoid synthesis via mevalonate and anthranilate degradation, known modulators of gram-positive bacterial growth and biofilm production, respectively. CONCLUSION: Heavy alcohol consumption appears to be the primary driver of changes in the circulating microbiome associated with a shift in its inferred metabolic functions. (Hepatology 2018;67:1284-1302).
Experiment 1
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Blood Portion of blood,Vertebrate blood,Whole blood,Blood
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatitis, Alcoholic acute alcoholic Hepatitis,acute alcoholic hepatitis,acute alcoholic liver disease,alcoholic Hepatitis,alcoholic hepatitis,Hepatitis, Alcoholic
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- NAC
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- alcoholics
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- alcoholic hepatitis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 56
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: figure 2B
Description: Differential group taxonomic features for non-alcohol consuming controls (NAC) and combined alcoholic group
Abundance in Group 1: increased abundance in alcoholics
| NCBI | Links |
|---|---|
| Bradyrhizobium ⚠ | |
| Microbacterium ⚠ | |
| Anaerocolumna | |
| Corynebacterium | |
| Peptostreptococcaceae | |
| Lachnospiraceae incertae sedis |
Signature 2
Needs review
Source: figure 2B
Description: Differential group taxonomic features for non-alcohol consuming controls (NAC) and combined alcoholic group
Abundance in Group 1: decreased abundance in alcoholics
Revision editor(s): WikiWorks
Experiment 2
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Blood Portion of blood,Vertebrate blood,Whole blood,Blood
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatitis, Alcoholic acute alcoholic Hepatitis,acute alcoholic hepatitis,acute alcoholic liver disease,alcoholic Hepatitis,alcoholic hepatitis,Hepatitis, Alcoholic
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- NAC
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HDC
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- alcoholic hepatitis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: figure 3C
Description: differential group taxonomic features for non-alcohol consuming controls (NAC) and heavy drinking control (HDC)
Abundance in Group 1: increased abundance in HDC
| NCBI | Links |
|---|---|
| Acinetobacter ⚠ | |
| Anaerococcus ⚠ | |
| Bradyrhizobium ⚠ | |
| Chryseobacterium ⚠ | |
| Kocuria ⚠ | |
| Leptotrichiaceae | |
| Microbacterium ⚠ | |
| Neisseria | |
| Phenylobacterium ⚠ | |
| Streptomyces | |
| Rhodobacter | |
| Peptostreptococcaceae |
Signature 2
Needs review
Source: figure 3C
Description: differential group taxonomic features for non-alcohol consuming controls (NAC) and heavy drinking control (HDC)
Abundance in Group 1: decreased abundance in HDC
Revision editor(s): WikiWorks
Experiment 3
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Blood Portion of blood,Vertebrate blood,Whole blood,Blood
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatitis, Alcoholic acute alcoholic Hepatitis,acute alcoholic hepatitis,acute alcoholic liver disease,alcoholic Hepatitis,alcoholic hepatitis,Hepatitis, Alcoholic
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- NAC
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- MAH
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- alcoholic hepatitis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: figure 3C
Description: differential group taxonomic features for non-alcohol consuming controls (NAC) and moderate alcoholic hepatitis(MAH)
Abundance in Group 1: increased abundance in MAH
| NCBI | Links |
|---|---|
| Peptostreptococcaceae | |
| Acinetobacter ⚠ | |
| Actinomyces | |
| Anaerococcus ⚠ | |
| Bradyrhizobium ⚠ | |
| Carnobacteriaceae | |
| Cloacibacterium | |
| Corynebacterium | |
| Curvibacter ⚠ | |
| Granulicatella | |
| Methylobacterium ⚠ |
Signature 2
Needs review
Source: figure 3C
Description: differential group taxonomic features for non-alcohol consuming controls (NAC) and moderate alcoholic hepatitis(MAH)
Abundance in Group 1: decreased abundance in MAH
Revision editor(s): WikiWorks
Experiment 4
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Blood Portion of blood,Vertebrate blood,Whole blood,Blood
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hepatitis, Alcoholic acute alcoholic Hepatitis,acute alcoholic hepatitis,acute alcoholic liver disease,alcoholic Hepatitis,alcoholic hepatitis,Hepatitis, Alcoholic
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- NAC
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- SAH
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- alcoholic hepatitis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
Lab analysis
- Sequencing type
- 16S
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: figure 3C
Description: differential group taxonomic features for non-alcohol consuming controls (NAC) and severe alcoholic hepatitis(SAH)
Abundance in Group 1: increased abundance in SAH
| NCBI | Links |
|---|---|
| Actinomyces | |
| Alloiococcus | |
| Brachybacterium ⚠ | |
| Corynebacterium | |
| Gillisia | |
| Microbacterium ⚠ | |
| Micromonosporaceae |
Signature 2
Needs review
Source: figure 3C
Description: differential group taxonomic features for non-alcohol consuming controls (NAC) and severe alcoholic hepatitis(SAH)
Abundance in Group 1: decreased abundance in SAH
Revision editor(s): WikiWorks
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