Alteration of Fecal Microbiota Profiles in Juvenile Idiopathic Arthritis. Associations with HLA-B27 Allele and Disease Status

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/21
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Di Paola M, Cavalieri D, Albanese D, Sordo M, Pindo M, Donati C, Pagnini I, Giani T, Simonini G, Paladini A, Lionetti P, De Filippo C, Cimaz R
Journal
Frontiers in microbiology
Year
2016
Keywords:
HLA-B27 allele, enthesitis-related arthritis, gut microbiota, juvenile idiopathic arthritis, metagenomics
Alteration of gut microbiota is involved in several chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, and gut microbial "pro-arthritogenic" profiles have been hypothesized. Intestinal inflammation may be involved in spondyloarthropathies and in a subset of patients affected by Juvenile Idiopathic Arthritis (JIA), the most common chronic rheumatic disease of childhood. We compared the fecal microbiota composition of JIA patients with healthy subjects (HS), evaluating differences in microbial profiles between sub-categories of JIA, such as enthesitis-related arthritis (JIA-ERA), in which inflammation of entheses occurs, and polyarticular JIA, non-enthesitis related arthritis (JIA-nERA). Through taxon-level analysis, we discovered alteration of fecal microbiota components that could be involved in subclinical gut inflammation, and promotion of joint inflammation. We observed abundance in Ruminococcaceae in both JIA categories, reduction in Clostridiaceae and Peptostreptococcaceae in JIA-ERA, and increase in Veillonellaceae in JIA-nERA, respectively, compared with HS. Among the more relevant genera, we found an increase in Clostridium cluster XIVb, involved in colitis and arthritis, in JIA-ERA patients compared with HS, and a trend of decrease in Faecalibacterium, known for anti-inflammatory properties, in JIA-nERA compared with JIA-ERA and HS. Differential abundant taxa identified JIA patients for the HLA-B27 allele, including Bilophila, Clostridium cluster XIVb, Oscillibacter, and Parvimonas. Prediction analysis of metabolic functions showed that JIA-ERA metagenome was differentially enriched in bacterial functions related to cell motility and chemotaxis, suggesting selection of potential virulence traits. We also discovered differential microbial profiles and intra-group variability among active disease and remission, suggesting instability of microbial ecosystem in autoimmune diseases with respect to healthy status. Similarly to other chronic autoimmune and inflammatory diseases, different microbial profiles, as observed among different JIA subgroups compared to HS, and potential functional acquisition related to migration, could promote inflammation and contribute to the disease pathogenesis.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/21

Curated date: 2021/11/20

Curator: Tislam

Revision editor(s): Claregrieve1, Tislam, Victoria

Subjects

Location of subjects
Italy
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
Juvenile idiopathic arthritis acute juvenile rheumatoid arthritis,Arthritis (juvenile idiopathic),arthritis, juvenile rheumatoid,breast myoepithelial carcinoma,chronic childhood arthritis,JIA,juvenile arthritis,juvenile chronic arthritis,Juvenile chronic arthritis (disorder),juvenile chronic polyarthritis,Juvenile idiopathic arthritis,juvenile idiopathic arthritis,Juvenile idiopathic arthritis (disorder),Juvenile rheumatoid a.,Juvenile Rheumatoid Arthritis,juvenile rheumatoid arthritis,Juvenile rheumatoid arthritis (disorder),Juvenile rheumatoid arthritis NOS (disorder),Juvenile rheumatoid arthritis, NOS,Juvenile seropositive polyarthritis,monarticular juvenile rheumatoid arthritis,pauciarticular juvenile arthritis,pauciarticular onset juvenile chronic arthritis,rheumatoid arthritis, systemic juvenile,systemic juvenile rheumatoid arthritis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HLAB27-
Group 1 name Corresponds to the case (exposed) group for case-control studies
HLAB27+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
enthesitis-related arthritis (JIA-ERA) patients with HLA-B27 allele
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
9
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V5-V6
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

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


Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/21

Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Claregrieve1, Tislam

Source: Figure 2, text

Description: Comparison of relative abundance of bacterial taxa between HLA-B27+ participants and HLB27- participants

Abundance in Group 1: decreased abundance in HLAB27+

NCBI Quality ControlLinks
Haemophilus
Pasteurellaceae
Eggerthella

Revision editor(s): Claregrieve1, Tislam

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/21

Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Fatima, Claregrieve1, Tislam

Source: Figure 2, text

Description: Comparison of relative abundance of bacterial taxa between HLA-B27+ participants and HLB27- participants

Abundance in Group 1: increased abundance in HLAB27+

NCBI Quality ControlLinks
Bilophila
Clostridium sp.
Dialister
Hydrogenoanaerobacterium
Lactobacillus
Oscillibacter
Parvimonas
Lactobacillaceae

Revision editor(s): Fatima, Claregrieve1, Tislam

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Fatima, Claregrieve1, Tislam, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
JIA patients with active disease
Group 1 name Corresponds to the case (exposed) group for case-control studies
JIA patients in remission
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
JIA patients with enthesitis-related arthritis who are in remission
Group 0 sample size Number of subjects in the control (unexposed) group
8
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Claregrieve1, Tislam

Source: Figure 4

Description: Differences in bacterial abundance between JIA patients with active disease and patients in remission

Abundance in Group 1: decreased abundance in JIA patients in remission

NCBI Quality ControlLinks
Sutterella

Revision editor(s): Claregrieve1, Tislam

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2021/11/30

Curator: Tislam

Revision editor(s): Claregrieve1, Tislam

Source: Figure 4

Description: Differences in bacterial abundance between JIA patients with active disease and patients in remission

Abundance in Group 1: increased abundance in JIA patients in remission

NCBI Quality ControlLinks
Clostridium sp.
Parasutterella
Odoribacter

Revision editor(s): Claregrieve1, Tislam

Experiment 3


Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2022/06/21

Curator: Claregrieve1

Revision editor(s): Claregrieve1, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy subjects
Group 1 name Corresponds to the case (exposed) group for case-control studies
JIA-ERA patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
enthesitis-related arthritis (JIA-ERA) patients
Group 0 sample size Number of subjects in the control (unexposed) group
29
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2022/06/21

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 1

Description: Differential microbial abundance between JIA-ERA patients and healthy controls

Abundance in Group 1: increased abundance in JIA-ERA patients

NCBI Quality ControlLinks
Oscillospiraceae
Clostridium sp.

Revision editor(s): Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2022/06/21

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 1

Description: Differential microbial abundance between JIA-ERA patients and healthy controls

Abundance in Group 1: decreased abundance in JIA-ERA patients

NCBI Quality ControlLinks
Peptostreptococcaceae
Clostridiaceae

Revision editor(s): Claregrieve1

Experiment 4


Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2022/06/21

Curator: Claregrieve1

Revision editor(s): Claregrieve1, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
JIA-nERA patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
polyarticular arthritis (JIA-ERA) patients
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/06/22

Curated date: 2022/06/21

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 1

Description: Differential microbial abundance between JIA-nERA patients and healthy controls

Abundance in Group 1: increased abundance in JIA-nERA patients

NCBI Quality ControlLinks
Oscillospiraceae
Veillonellaceae

Revision editor(s): Claregrieve1