Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/9

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

29180991

DOI Digital object identifier for electronic documents.

10.3389/fmicb.2017.02222

URI

Authors

Wang J, Wang Y, Zhang X, Liu J, Zhang Q, Zhao Y, Peng J, Feng Q, Dai J, Sun S, Zhao Y, Zhao L, Zhang Y, Hu Y, Zhang M

Journal

Frontiers in microbiology

Year

2017

Keywords:

16S rRNA gene sequencing, aromatic amino acids, chronic hepatitis B, gut sysbiosis, serum metabolomics

Chronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to severe liver failure, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Previous evidence has indicated that the dysbiosis of gut microbiota occurs after liver virus infection and is associated with severe liver disease. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in early-stage CHB and to understand their influence on disease progression. We investigated the gut microbial composition of stool samples from 85 CHB patients with low Child-Pugh scores and 22 healthy controls using the Illumina MiSeq sequencing platform. Furthermore, the serum metabolome of 40 subjects was measured by gas chromatography mass spectrometry. Compared with the controls, significant alteration in the gut microbiota was observed in the CHB patients; 5 operational taxonomic units (OTUs) belonging to Actinomyces, Clostridium sensu stricto, unclassified Lachnospiraceae and Megamonas were increased, and 27 belonging to Alistipes, Asaccharobacter, Bacteroides, Butyricimonas, Clostridium IV, Escherichia/Shigella, Parabacteroides, Ruminococcus, unclassified Bacteria, unclassified Clostridiales, Unclassified Coriobacteriaceae, unclassified Enterobacteriaceae, unclassified Lachnospiraceae and unclassified Ruminococcaceae were decreased. The inferred metagenomic information of gut microbiota in CHB showed 21 enriched and 17 depleted KEGG level-2 pathways. Four OTUs, OTU38 (Streptococcus), OTU124 (Veillonella), OTU224 (Streptococcus), and OTU55 (Haemophilus), had high correlations with hosts' hepatic function indices and 10 serum metabolites, including phenylalanine and tyrosine, which are aromatic amino acids that play pathogenic roles in liver disease. In particular, these 4 OTUs were significantly higher in patients with higher Child-Pugh scores, who also showed diminished phenylalanine and tryptophan metabolisms in the inferred gut metagenomic functions. These compositional and functional changes in the gut microbiota in early-stage CHB patients suggest the potential contributions of gut microbiota to the progression of CHB, and thus provide new insight into gut microbiota-targeted interventions to improve the prognosis of this disease.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/9

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Subjects

Location of subjects: China

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: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Chronic hepatitis B virus infection chronic Hepatitis B,chronic hepatitis B infection,chronic hepatitis B virus infection,hepatitis B infection, chronic,hepatitis B, chronic,Chronic hepatitis B virus infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: chronic hepatitis B patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Chronic hepatitis B patients

Group 0 sample size Number of subjects in the control (unexposed) group: 22

Group 1 sample size Number of subjects in the case (exposed) group: 85

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

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

Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, sex

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: unchanged

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

Richness Number of species: unchanged

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/9

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): Claregrieve1, WikiWorks

Source: Table 2

Description: Differential microbial abundance between chronic hepatitis patients and controls

Abundance in Group 1: increased abundance in chronic hepatitis B patients

NCBI	Quality Control	Links
Megamonas
Actinomyces
Clostridium sp.
Lachnospiraceae

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Edit History Delete

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Reviewed Marked as Reviewed by Claregrieve1 on 2023/01/9

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): Fatima, Claregrieve1, WikiWorks

Source: Table 2

Description: Differential microbial abundance between chronic hepatitis patients and controls

Abundance in Group 1: decreased abundance in chronic hepatitis B patients

NCBI	Quality Control	Links
Bacteroides
Butyricimonas
Parabacteroides
Porphyromonadaceae
unclassified Enterobacteriaceae
unclassified Lachnospiraceae
Clostridiales bacterium
Asaccharobacter
Coriobacteriaceae
Escherichia/Shigella sp.
Enterobacteriaceae
Alistipes
Ruminococcus
Oscillospiraceae

Revision editor(s): Fatima, Claregrieve1, WikiWorks