A metagenomic study of the gut microbiome in Behcet's disease

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Ye Z, Zhang N, Wu C, Zhang X, Wang Q, Huang X, Du L, Cao Q, Tang J, Zhou C, Hou S, He Y, Xu Q, Xiong X, Kijlstra A, Qin N, Yang P
Journal
Microbiome
Year
2018
Keywords:
Behcet’s disease, Fecal microbiota transplant, Gut microbiome, Metagenomic analysis
BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease. METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD. RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ. CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.

Experiment 1


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

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
Behcet's syndrome Adamantiades-Behcet disease,BD,Bechet syndrome,BEHCET DIS,Behcet Disease,Behcet disease,Behcet syndrome,Behcet's disease,Behcet's syndrome,Behcets Syndrome,Behet's syndrome,Behet's syndrome (disorder),Behçet disease,Behçet syndrome,Behçet's disease,Behçet's syndrome,Behçet-Adamantiades syndrome,Behçet’s disease,Morbus Behçet's syndrome,silk road disease,triple symptom complex,Triple-Symptom Complex,behcet's syndrome
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Untreated active Behcet's disease (BD) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Active BD was defined according to presence of active intraocular inflammation (case-control)
Group 0 sample size Number of subjects in the control (unexposed) group
52
Group 1 sample size Number of subjects in the case (exposed) group
24
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
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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, body mass index, sex


Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Welile, ChiomaBlessing

Source: Figure 2a

Description: Differentially abundant genera in Behcet's disease subjects compared to healthy controls.

Abundance in Group 1: increased abundance in Untreated active Behcet's disease (BD) patients

NCBI Quality ControlLinks
Alistipes ihumii
Alistipes sp. HGB5
Azospirillum sp. CAG:239
Bacteroides
Bacteroides eggerthii CAG:109
Bacteroides sp. CAG:770
Bilophila sp. 4_1_30
Bilophila wadsworthia
Collinsella aerofaciens
Collinsella sp. 4_8_47FAA
Collinsella sp. CAG:166
Eubacterium sp. CAG:202
Firmicutes bacterium CAG:240
Firmicutes bacterium CAG:83
Fusobacterium sp. CAG:815
Mitsuokella multacida
Oscillibacter sp. KLE 1728
Oscillibacter sp. KLE 1745
Oscillospiraceae bacterium VE202-24
Paraprevotella clara CAG:116
Phocaeicola coprophilus CAG:333
Ruminococcaceae bacterium cv2
uncultured crAssphage

Revision editor(s): Fiddyhamma, Welile, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

Source: Figure 2a

Description: Differentially abundant genera in Behcet's disease subjects compared to healthy controls.

Abundance in Group 1: decreased abundance in Untreated active Behcet's disease (BD) patients

NCBI Quality ControlLinks
Acidiphilium sp. CAG:727
Alistipes sp. CAG:268
Anaerotruncus sp. CAG:528
Clostridium sp. CAG:1024
Clostridium sp. CAG:127
Clostridium sp. CAG:349
Clostridium sp. CAG:813
Coprococcus sp. CAG:782
Dialister invisus
Eubacterium sp. CAG:38
Fusobacterium mortiferum
Megasphaera elsdenii CAG:570
Methanoculleus sp. CAG:1088
Methanomethylophilus alvi
Pyramidobacter piscolens
Subdoligranulum sp. CAG:314

Revision editor(s): Fiddyhamma, ChiomaBlessing

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Behcet's disease (case-control)
Group 0 sample size Number of subjects in the control (unexposed) group
43
Group 1 sample size Number of subjects in the case (exposed) group
15

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4

Statistical Analysis

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


Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

Source: Supplementary Figure S2, Supplementary Table S8

Description: Differences in altered oral microbial composition in Behcet's disease (BD) patients compared to healthy controls

Abundance in Group 1: increased abundance in Untreated active Behcet's disease (BD) patients

NCBI Quality ControlLinks
Allobaculum
Alloscardovia
Atopobium
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Butyrivibrio
Coriobacteriaceae
Coriobacteriales
Corynebacteriaceae
Corynebacterium
Desulfovibrio
Lactobacillaceae
Lactobacillus
Mobiluncus
Prevotella
Scardovia
Turicibacter
Turicibacteraceae
unclassified Paraprevotella
turicibacteralesturicibacterales

Revision editor(s): Fiddyhamma, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/12

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, Omojokunoluwatomisin, ChiomaBlessing

Source: Supplementary Figure S2, Supplementary Table S8

Description: Differences in altered oral microbial composition in Behcet's disease (BD) patients compared to healthy controls

Abundance in Group 1: decreased abundance in Untreated active Behcet's disease (BD) patients

NCBI Quality ControlLinks
Betaproteobacteria
Neisseriaceae
Neisseriales
Pseudomonadota

Revision editor(s): Fiddyhamma, Omojokunoluwatomisin, ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

Differences from previous experiment shown

Subjects

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
Response to transplant Response to transplant,response to transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy Control feces treated group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Behcet's disease (BD) feces treated group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
B10RIII mice (mice undergoing autoimmune uveitis) colonized with untreated BD patients stool samples (experimental)
Group 0 sample size Number of subjects in the control (unexposed) group
4
Group 1 sample size Number of subjects in the case (exposed) group
4
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None
Sequencing type
Not specified
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Not specified

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified
Matched on Factors on which subjects have been matched on in a case-control study
Not specified

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

Source: Supplementary Figure S1c, Supplementary Table S9

Description: Abundance of altered genera in Behcet's disease (BD) patients’ feces treated group compared to healthy control feces treated mice

Abundance in Group 1: increased abundance in Behcet's disease (BD) feces treated group

NCBI Quality ControlLinks
Alistipes
Alloprevotella
Anaerofilum
Bilophila
Butyricimonas
Coprobacter
Mucispirillum
Paraprevotella
Clostridium IVClostridium IV

Revision editor(s): Fiddyhamma, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/08

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, ChiomaBlessing

Source: Supplementary Figure S1c, Supplementary Table S9

Description: Abundance of altered genera in Behcet's disease (BD) patients’ feces treated group compared to healthy control feces treated mice

Abundance in Group 1: decreased abundance in Behcet's disease (BD) feces treated group

NCBI Quality ControlLinks
Collinsella

Revision editor(s): Fiddyhamma, ChiomaBlessing

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/29

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Behcet's syndrome Adamantiades-Behcet disease,BD,Bechet syndrome,BEHCET DIS,Behcet Disease,Behcet disease,Behcet syndrome,Behcet's disease,Behcet's syndrome,Behcets Syndrome,Behet's syndrome,Behet's syndrome (disorder),Behçet disease,Behçet syndrome,Behçet's disease,Behçet's syndrome,Behçet-Adamantiades syndrome,Behçet’s disease,Morbus Behçet's syndrome,silk road disease,triple symptom complex,Triple-Symptom Complex,behcet's syndrome
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy Control
Group 1 name Corresponds to the case (exposed) group for case-control studies
Untreated active Behcet's disease (BD) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Active BD was defined according to presence of active intraocular inflammation (case-control)
Group 0 sample size Number of subjects in the control (unexposed) group
52
Group 1 sample size Number of subjects in the case (exposed) group
24
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
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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


Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/29

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental. Table S3

Description: Enriched/ depleted species in Behcet's disease subjects compared to healthy controls

Abundance in Group 1: increased abundance in Untreated active Behcet's disease (BD) patients

NCBI Quality ControlLinks
Atkinsonella texensis
Epichloe aotearoae
Macrophomina phaseolina
Stenotrophomonas sp. Leaf70
Diaporthe ampelina
Colletotrichum higginsianum
Drechslerella stenobrocha
Trichoderma parareesei
Cladophialophora psammophila
Colletotrichum orbiculare
Stenotrophomonas rhizophila
Actinomyces sp. ph3
Candida parapsilosis
Claviceps paspali
Corynebacterium argentoratense
Exophiala mesophila
Ogataea methanolica
Actinomyces graevenitzii
Stenotrophomonas maltophilia
Shiraia sp. slf14
Neurospora crassa

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-29

Curated date: 2024/03/29

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental. Table S3

Description: Enriched/ depleted species in Behcet's disease subjects compared to healthy controls

Abundance in Group 1: decreased abundance in Untreated active Behcet's disease (BD) patients

NCBI Quality ControlLinks
Acinetobacter sp. CAG:196
Epichloe glyceriae

Revision editor(s): ChiomaBlessing