Lower gut microbiome diversity and higher abundance of proinflammatory genus Collinsella are associated with biopsy-proven nonalcoholic steatohepatitis

Study information

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study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

31696774

DOI Digital object identifier for electronic documents.

10.1080/19490976.2019.1681861

URI Uniform resource identifier for web resources.

https://pubmed.ncbi.nlm.nih.gov/31696774/

Authors

Astbury S, Atallah E, Vijay A, Aithal GP, Grove JI, Valdes AM

Journal

Gut microbes

Year

2020

There is increasing evidence for the role of gut microbial composition in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is the most serious form of NAFLD where inflammation causes liver damage that can progress to cirrhosis. We have characterized the gut microbiome composition in UK patients with biopsy-proven NASH (n = 65) and compared it to that in healthy controls (n = 76). We report a 7% lower Shannon alpha diversity in NASH patients without cirrhosis (n = 40) compared to controls (p = 2.7x 10-4) and a 14% drop in NASH patients with cirrhosis (n = 25, p = 5.0x 10-4). Beta diversity (Unweighted UniFrac distance) was also significantly reduced in both NASH (p = 5.6x 10-25) and NASH-cirrhosis (p = 8.1x 10-7) groups. The genus most strongly associated with NASH in this study was Collinsella (0.29% abundance in controls, 3.45% in NASH without cirrhosis (False Discovery Rate (FDR) p = .008), and 4.38% in NASH with cirrhosis (FDR p = .02)). This genus, which has been linked previously to obesity and atherosclerosis, was also positively correlated with fasting levels of triglycerides (p = .01) and total cholesterol (p = 1.2x 10-4) and negatively correlated with high-density lipoprotein cholesterol (p = 2.8x 10-6) suggesting that some of the pathways present in this microbial genus may influence lipid metabolism in the host. In patients, we also found decreased abundance of some of the Ruminococcaceae which are known to produce high levels of short-chain fatty acids which can lower inflammation. This may thus contribute to pathology associated with NASH.

Experiment 1

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Curated date: 2021/08/11

Curator: Madhubani Dey

Revision editor(s): WikiWorks753, Madhubani Dey

Subjects

Location of subjects

United Kingdom

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

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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

non-alcoholic steatohepatitis NASH,nash - nonalcoholic Steatohepatitis,non alcoholic steatohepatitis,non-alcoholic steatohepatitis,nonalcoholic Steatohepatitis,nonalcoholic steatohepatitis

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

Individuals diagnosed with Nonalcoholic steatohepatitis (without cirrhosis)

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

Individuals diagnosed with Nonalcoholic steatohepatitis (without cirrhosis); The Fatty Liver Inhibition of Progression (FLIP) Consortium algorithm was used as a diagnostic indicator where the histological diagnosis of NASH requires the presence of steatosis, ballooning, and lobular inflammation

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

76

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

40

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Statistical test

Kruskall-Wallis

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)?

Yes

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

decreased

Signature 1

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Curated date: 2021/08/11

Curator: Madhubani Dey

Revision editor(s): Madhubani Dey

Source: Figure 4

Description: Increased abundance of bacterial communities in individuals diagnosed with Nonalcoholic steatohepatitis (without cirrhosis)

Abundance in Group 1: increased abundance in Individuals diagnosed with Nonalcoholic steatohepatitis (without cirrhosis)

NCBI	Links
Actinomyces
Collinsella
Eggerthella
Fusicatenibacter
Hungatella
Lachnoclostridium
Lachnospiraceae bacterium
Rhodospirillaceae

Revision editor(s): Madhubani Dey

Signature 2

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Curated date: 2021/08/11

Curator: Madhubani Dey

Revision editor(s): Madhubani Dey

Source: Figure 4

Description: Decreased abundance of bacterial communities in individuals diagnosed with Nonalcoholic steatohepatitis (without cirrhosis)

Abundance in Group 1: decreased abundance in Individuals diagnosed with Nonalcoholic steatohepatitis (without cirrhosis)

NCBI	Links
Alistipes
Bacteroides
Barnesiella
Desulfovibrio
Lachnospiraceae bacterium NC2004
Odoribacter
Oscillospiraceae bacterium
Parabacteroides
Paraprevotella
Parasutterella
Peptoclostridium
Porphyromonadaceae
Terrisporobacter
Mollicutes RF9Mollicutes RF9
Ruminococcaceae UCG-010Ruminococcaceae UCG-010
Ruminococcaceae UCG-014Ruminococcaceae UCG-014
Clostridium sensu stricto 1Clostridium sensu stricto 1
Clostridiales vadin BB60 groupClostridiales vadin BB60 group
Christensenellaceae R-7 groupChristensenellaceae R-7 group

Revision editor(s): Madhubani Dey

Experiment 2

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

Needs review

Curated date: 2021/08/11

Curator: Madhubani Dey

Revision editor(s): WikiWorks753, Madhubani Dey

Subjects

Location of subjects

United Kingdom

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

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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

non-alcoholic steatohepatitis NASH,nash - nonalcoholic Steatohepatitis,non alcoholic steatohepatitis,non-alcoholic steatohepatitis,nonalcoholic Steatohepatitis,nonalcoholic steatohepatitis

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

Individuals diagnosed with Nonalcoholic steatohepatitis (NASH) with cirrhosis

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

Individuals diagnosed with Nonalcoholic steatohepatitis (NASH) with cirrhosis; The Fatty Liver Inhibition of Progression (FLIP) Consortium algorithm was used as a diagnostic indicator where the histological diagnosis of NASH requires the presence of steatosis, ballooning, and lobular inflammation; Fibrosis was scored following the CRN grading system54 by a single pathologist.

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

76

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

25

Lab analysis

Sequencing type

16S

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Statistical test

Kruskall-Wallis

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)?

Yes

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

decreased

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/08/11

Curator: Madhubani Dey

Revision editor(s): Madhubani Dey

Source: Figure 4

Description: Increased abundance of bacterial communities in individuals diagnosed with Nonalcoholic steatohepatitis (NASH) with cirrhosis

Abundance in Group 1: increased abundance in Individuals diagnosed with Nonalcoholic steatohepatitis (NASH) with cirrhosis

NCBI	Links
Actinomyces
Collinsella
Eggerthella
Hungatella
Lachnoclostridium

Revision editor(s): Madhubani Dey

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/08/11

Curator: Madhubani Dey

Revision editor(s): Madhubani Dey

Source: Figure 4

Description: Decreased abundance of bacterial communities in individuals diagnosed with Nonalcoholic steatohepatitis (NASH) with cirrhosis

Abundance in Group 1: decreased abundance in Individuals diagnosed with Nonalcoholic steatohepatitis (NASH) with cirrhosis

NCBI	Links
Alistipes
Bacteroides
Barnesiella
Odoribacter
Parabacteroides
Peptoclostridium
Ruminiclostridium sp.
Terrisporobacter
unclassified Porphyromonadaceae
Lachnospiraceae NC2004Lachnospiraceae NC2004
Ruminococcaceae UCG-014Ruminococcaceae UCG-014
Christensenellaceae R-7 groupChristensenellaceae R-7 group
Clostridium sensu stricto 1Clostridium sensu stricto 1

Revision editor(s): Madhubani Dey