The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis

From BugSigDB
Reviewed Marked as Reviewed by Lwaldron on 2023-6-7
Quality issues
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
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,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,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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
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

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Lwaldron, WikiWorks

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 Quality ControlLinks
Bradyrhizobium
Microbacterium
Anaerocolumna
Corynebacterium
Peptostreptococcaceae
Lachnospiraceae incertae sedis

Revision editor(s): Lwaldron, WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

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

NCBI Quality ControlLinks
Gordonia
Nocardioides
Friedmanniella
Bifidobacterium
Bacteroides
Barnesiella
Paraprevotella
Prevotella
Alistipes
Flavobacterium
Oceanobacillus
Thermicanus
Blautia
Ruminococcus
Microvirga
Paracoccus
Rickettsia
Tepidimonas
Acidovorax
Hydrogenophaga
Caldimonas
Janthinobacterium
Hydrogenophilus
Aeromonas

Revision editor(s): WikiWorks

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
HDC
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Lwaldron, WikiWorks

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 Quality ControlLinks
Acinetobacter
Anaerococcus
Bradyrhizobium
Chryseobacterium
Kocuria
Leptotrichiaceae
Microbacterium
Neisseria
Phenylobacterium
Streptomyces
Rhodobacter
Peptostreptococcaceae

Revision editor(s): Lwaldron, WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

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

NCBI Quality ControlLinks
Gordonia
Nocardioides
Bifidobacterium
Bacteroidales
Bacteroides
Barnesiella
Porphyromonadaceae
Prevotellaceae
Prevotella
Flavobacterium
Streptococcus
Clostridium
Tepidimonas
Acidovorax
Hydrogenophilus
Azotobacter group

Revision editor(s): WikiWorks

Experiment 3


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
MAH
Group 1 sample size Number of subjects in the case (exposed) group
18

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Lwaldron, WikiWorks

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 Quality ControlLinks
Peptostreptococcaceae
Acinetobacter
Actinomyces
Anaerococcus
Bradyrhizobium
Carnobacteriaceae
Cloacibacterium
Corynebacterium
Curvibacter
Granulicatella
Methylobacterium

Revision editor(s): Lwaldron, WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

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

NCBI Quality ControlLinks
Nocardioides
Friedmanniella
Actinomycetales
Bacteroidales
Porphyromonadaceae
Prevotella
Prevotellaceae
Flavobacterium
Bacillus
Clostridium
Sphingomonadaceae
Janthinobacterium
Burkholderiales
Hydrogenophilus
Aeromonadaceae
Azotobacter group

Revision editor(s): WikiWorks

Experiment 4


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
SAH
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): Atrayees, WikiWorks

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 Quality ControlLinks
Actinomyces
Alloiococcus
Brachybacterium
Corynebacterium
Gillisia
Microbacterium
Micromonosporaceae

Revision editor(s): Atrayees, WikiWorks

Signature 2

Needs review

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

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

NCBI Quality ControlLinks
Acidimicrobiales
Microbacteriaceae
Nocardioides
Actinomycetales
Bifidobacterium
Bacteroidales
Barnesiella
Porphyromonadaceae
Prevotellaceae
Alistipes
Flavobacterium
Chitinophagaceae
Cytophagaceae

Revision editor(s): WikiWorks