Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

Study information

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study design

Citation

PMID PubMed identifier for scientific articles.

24192039

DOI Digital object identifier for electronic documents.

10.7554/eLife.01202

URI Uniform resource identifier for web resources.

Authors

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR

Journal

eLife

Year

2013

Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.001.

Experiment 1

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Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Tislam

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

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: new-onset rheumatoid arthritis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: new-onset rheumatoid arthritis
Group 0 sample size Number of subjects in the control (unexposed) group: 44
Group 1 sample size Number of subjects in the case (exposed) group: 28
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): recent (<3 months prior) use of any antibiotic therapy

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V2

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Sequencing platform: "Titanium" is not in the list (DNA-DNA Hybridization, Human Intestinal Tract Chip, Illumina, Ion Torrent, Non-quantitative PCR, PacBio RS, PhyloChip, Roche454, RT-qPCR, Mass spectrometry, ...) of allowed values.Titanium

Statistical Analysis

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): .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

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Signature 1

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Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Tislam, Lwaldron, Aiyshaaaa

Source: Figure 1, text

Description: Figure 1.. Differences in the relative abundance of Prevotella and Bacteroides in 114 subjects with and without arthritis, determined by 16S sequencing (regions V1–V2, 454 platform). (A) LEfSe (Segata et al., 2011) was used to compare the abundances of all detected clades among all groups, producing an effect size for each comparison (‘Materials and methods’). All results shown are highly significant (q<0.01) by Kruskal-Wallis test adjusted with the Benjamini-Hochberg procedure for multiple testing, except that indicated with an asterisk, which is significant at q<0.05. Negative values (left) correspond to effect sizes representative of NORA groups, while positive values (right) correspond to effect sizes in HLT subjects. Prevotella was found to be over-represented in NORA patients, while Bacteroides was over-represented in all other groups.

Abundance in Group 1: decreased abundance in new-onset rheumatoid arthritis

NCBI	Links
Bacteroidaceae
Bacteroides
Lachnospiraceae
Phascolarctobacterium
clostridia group xivclostridia group xiv
Oscillospiraceae

Revision editor(s): Tislam, Lwaldron, Aiyshaaaa

Signature 2

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incomplete

Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Tislam

Source: Figure 1

Description: Figure 1.. Differences in the relative abundance of Prevotella and Bacteroides in 114 subjects with and without arthritis, determined by 16S sequencing (regions V1–V2, 454 platform). (A) LEfSe (Segata et al., 2011) was used to compare the abundances of all detected clades among all groups, producing an effect size for each comparison (‘Materials and methods’). All results shown are highly significant (q<0.01) by Kruskal-Wallis test adjusted with the Benjamini-Hochberg procedure for multiple testing, except that indicated with an asterisk, which is significant at q<0.05. Negative values (left) correspond to effect sizes representative of NORA groups, while positive values (right) correspond to effect sizes in HLT subjects. Prevotella was found to be over-represented in NORA patients, while Bacteroides was over-represented in all other groups.

Abundance in Group 1: increased abundance in new-onset rheumatoid arthritis

NCBI	Links
Prevotella
Catenibacterium
Veillonella
Veillonella sp.
Prevotellaceae

Revision editor(s): Tislam