An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/8

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

27102666

DOI Digital object identifier for electronic documents.

10.1186/s13073-016-0299-7

URI

Authors

Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J, Nelson H, Matteson EL, Taneja V

Journal

Genome medicine

Year

2016

BACKGROUND: The adaptive immune response in rheumatoid arthritis (RA) is influenced by an interaction between host genetics and environment, particularly the host microbiome. Association of the gut microbiota with various diseases has been reported, though the specific components of the microbiota that affect the host response leading to disease remain unknown. However, there is limited information on the role of gut microbiota in RA. In this study we aimed to define a microbial and metabolite profile that could predict disease status. In addition, we aimed to generate a humanized model of arthritis to confirm the RA-associated microbe. METHODS: To identify an RA biomarker profile, the 16S ribosomal DNA of fecal samples from RA patients, first-degree relatives (to rule out environment/background as confounding factors), and random healthy non-RA controls were sequenced. Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link. The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis. RESULTS: Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels. A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria, with a decrease in abundant taxa in patients with RA compared with controls. Prediction models based on the random forests algorithm suggested that three genera, Collinsella, Eggerthella, and Faecalibacterium, segregated with RA. The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A. A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis. CONCLUSIONS: These observations suggest dysbiosis in RA patients resulting from the abundance of certain rare bacterial lineages. A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/8

Curated date: 2021/08/16

Curator: Tislam

Revision editor(s): WikiWorks, Rimsha, Claregrieve1, Tislam, 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: 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: Rheumatoid arthritis Arthritis or polyarthritis, rheumatic,arthritis or polyarthritis, rheumatic,Arthritis, Rheumatoid,arthritis, rheumatoid,atrophic Arthritis,atrophic arthritis,autoimmune arthritis,Chronic rheumatic arthritis,Proliferative arthritis,RA,RA - Rheumatoid arthritis,RhA - Rheumatoid arthritis,Rheumatic gout,rheumatoid arthritis,Rheumatoid arthritis (disorder),Rheumatoid arthritis NOS,Rheumatoid arthritis NOS (disorder),rheumatoid arthritis, susceptibility to,Rheumatoid disease,Rheumatoid arthritis

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: rheumatoid arthritis patients

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

Group 0 sample size Number of subjects in the control (unexposed) group: 32

Group 1 sample size Number of subjects in the case (exposed) group: 40

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Any patient or control on antibiotics, consuming probiotics, or having a known history of inflammatory bowel disease or other autoimmune diseases like diabetes and multiple sclerosis were excluded.

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V5

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)?: Yes

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, sex

Alpha Diversity

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

Richness Number of species: decreased

Signature 1

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Curated date: 2021/08/16

Curator: Tislam

Revision editor(s): Rimsha, Claregrieve1, Tislam, Merit

Source: Figure 3, text

Description: Differential microbial abundance between healthy controls and RA patients

Abundance in Group 1: increased abundance in rheumatoid arthritis patients

NCBI	Quality Control	Links
Actinomyces
Actinomycetaceae
Actinomycetales
Actinomycetota
Bacilli
Coriobacteriaceae
Coriobacteriales
Coriobacteriia
Eggerthella
Erwinia
Eubacteriaceae
Eubacterium
Lactobacillales
Streptococcaceae
Streptococcus
Turicibacter
Turicibacteraceae
unclassified Actinomycetota