Dysbiosis in the Gut Microbiota in Patients with Inflammatory Bowel Disease during Remission

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Pisani A, Rausch P, Bang C, Ellul S, Tabone T, Marantidis Cordina C, Zahra G, Franke A, Ellul P
Journal
Microbiology spectrum
Year
2022
Keywords:
Enterobacteriaceae, dysbiosis, flavonoid-degrading bacteria, inflammatory bowel disease, microbiota, remission
Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory disorder which comprises two main conditions: Crohn's disease (CD) and ulcerative colitis (UC). Although the etiology of IBD has not been fully elucidated, the gut microbiota is hypothesized to play a vital role in its development. The aim of this cross-sectional study was to characterize the fecal microbiota in CD or UC patients in a state of remission to reveal potential factors sustaining residual levels of inflammation and triggering disease relapses. Ninety-eight IBD patients in a state of clinical remission (66 UC, 32 CD) and 97 controls were recruited, and stool samples, as well as detailed patient data, were collected. After DNA extraction, the variable regions V1 and V2 of the 16S rRNA gene were amplified and sequenced. Patients with IBD had a decrease in alpha diversity compared to that of healthy controls, and the beta diversity indices showed dissimilarity between the cohorts. Healthy controls were associated with the beneficial organisms unclassified Akkermansia species (Akkermansia uncl.), Oscillibacter uncl., and Coprococcus uncl., while flavonoid-degrading bacteria were associated with IBD. Network analysis identified highly central and influential disease markers and a strongly correlated network module of Enterobacteriaceae which was associated with IBD and could act as drivers for residual inflammatory processes sustaining and triggering IBD, even in a state of low disease activity. The microbiota in IBD patients is significantly different from that of healthy controls, even in a state of remission, which implicates the microbiota as an important driver of chronicity in IBD. IMPORTANCE Dysbiosis in inflammatory bowel disease (IBD) has been implicated as a causal or contributory factor to the pathogenesis of the disease. This study, done on patients in remission while accounting for various confounding factors, shows significant community differences and altered community dynamics, even after acute inflammation has subsided. A cluster of Enterobacteriaceae was linked with Crohn's disease, suggesting that this cluster, which contains members known to disrupt colonization resistance and form biofilms, persists during quiescence and can lead to chronic inflammation. Flavonoid-degrading bacteria were also associated with IBD, raising the possibility that modification of dietary flavonoids might induce and maintain remission in IBD.

Experiment 1


Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19, Victoria

Subjects

Location of subjects
Malta
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
Ulcerative colitis colitis ulcerative,Colitis, Ulcerative,Left-sided ulcerative (chronic) colitis,Left-sided ulcerative colitis,left-sided ulcerative colitis,Other ulcerative colitis,Other ulcerative colitis (disorder),UC - ulcerative colitis,ulcerative colitis,ulcerative colitis (disease),ulcerative colitis (disorder),Ulcerative colitis, unspecified,ULCERATVE COLITIS UNSPCF,Ulcerative colitis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls (HC)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Ulcerative colitis (UC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Ulcerative colitis (UC) in a state of remission
Group 0 sample size Number of subjects in the control (unexposed) group
97
Group 1 sample size Number of subjects in the case (exposed) group
66
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
V1-V2
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).
raw counts
Statistical test
DESeq2
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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 5

Description: Analyses of differential abundances at lower taxonomic levels with respect to IBD status/health condition

Abundance in Group 1: increased abundance in Ulcerative colitis (UC)

NCBI Quality ControlLinks
Dialister invisus
Flavonifractor plautii
unclassified Acidaminococcus
unclassified Bacteroides
unclassified Faecalibacterium
unclassified Oscillospiraceae
unclassified Parabacteroides
unclassified Parasutterella
unclassified Oscillibacter

Revision editor(s): Samreen-19

Signature 2

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 5

Description: Analyses of differential abundances at lower taxonomic levels with respect to IBD status/health condition

Abundance in Group 1: decreased abundance in Ulcerative colitis (UC)

NCBI Quality ControlLinks
unclassified Alistipes
unclassified Coprococcus
unclassified Oxalobacter
Akkermansia muciniphila
unclassified Bacteroides
unclassified Lachnospiraceae
unclassified Oscillibacter
unclassified Eubacteriales
unclassified Anaerostipes
unclassified Faecalibacterium
Haemophilus parainfluenzae
unclassified Sutterella

Revision editor(s): Samreen-19

Experiment 2


Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Crohn’s disease (CD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Crohn’s disease (CD) in a state of remission
Group 1 sample size Number of subjects in the case (exposed) group
32

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 5

Description: Analyses of differential abundances at lower taxonomic levels with respect to IBD status/health condition

Abundance in Group 1: increased abundance in Crohn’s disease (CD)

NCBI Quality ControlLinks
Dialister invisus
Flavonifractor plautii
unclassified Dorea
unclassified Oscillospiraceae
unclassified Subdoligranulum
unclassified Escherichia
unclassified Oscillibacter
unclassified Bacteroides
unclassified Acidaminococcus

Revision editor(s): Samreen-19

Signature 2

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 5

Description: Analyses of differential abundances at lower taxonomic levels with respect to IBD status/health condition

Abundance in Group 1: decreased abundance in Crohn’s disease (CD)

NCBI Quality ControlLinks
unclassified Alistipes
unclassified Coprococcus
unclassified Oxalobacter
Akkermansia muciniphila
unclassified Bacteroides
unclassified Lachnospiraceae
unclassified Oscillibacter
unclassified Eubacteriales
unclassified Anaerostipes
unclassified Faecalibacterium
Haemophilus parainfluenzae
unclassified Sutterella

Revision editor(s): Samreen-19

Experiment 3


Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Gut microbiome measurement Gut microbiome measurement,gut microbiome measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Crohn's disease (CD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Ulcerative colitis (UC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Ulcerative colitis (UC) in a state of remission
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
66

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 5

Description: Analyses of differential abundances at lower taxonomic levels with respect to IBD status/health condition

Abundance in Group 1: increased abundance in Ulcerative colitis (UC)

NCBI Quality ControlLinks
unclassified Parabacteroides
unclassified Faecalibacterium
unclassified Parasutterella

Revision editor(s): Samreen-19

Signature 2

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 5

Description: Analyses of differential abundances at lower taxonomic levels with respect to IBD status/health condition

Abundance in Group 1: decreased abundance in Ulcerative colitis (UC)

NCBI Quality ControlLinks
unclassified Dorea
unclassified Subdoligranulum
unclassified Escherichia

Revision editor(s): Samreen-19

Experiment 4


Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Smoking behavior smoking,Smoking behavior,smoking behavior
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No
Group 1 name Corresponds to the case (exposed) group for case-control studies
Yes
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Inflammatory Bowel Disease (IBD) who are smokers
Group 0 sample size Number of subjects in the control (unexposed) group
63
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 9

Description: Differential abundance analysis for smoking behaviour

Abundance in Group 1: increased abundance in Yes

NCBI Quality ControlLinks
unclassified Lachnospiraceae
unclassified Bacteroides
unclassified Faecalibacterium
unclassified Sutterella

Revision editor(s): Samreen-19

Signature 2

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 9

Description: Differential abundance analysis for smoking behaviour

Abundance in Group 1: decreased abundance in Yes

NCBI Quality ControlLinks
Bacteroides ovatus
Phocaeicola dorei
unclassified Anaerostipes
unclassified Bacteroides
unclassified Bilophila
unclassified Faecalibacterium
unclassified Oscillospiraceae
unclassified Parasutterella
unclassified Citrobacter

Revision editor(s): Samreen-19

Experiment 5


Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19, Victoria

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Ex
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Inflammatory Bowel Disease (IBD) who were ex-smokers (had stopped smoking for at least 6 months).
Group 1 sample size Number of subjects in the case (exposed) group
15

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 9

Description: Differential abundance analysis for smoking behaviour

Abundance in Group 1: increased abundance in Ex

NCBI Quality ControlLinks
Phocaeicola dorei
unclassified Lachnospiraceae
unclassified Bacteroides
unclassified Parasutterella
unclassified Faecalibacterium

Revision editor(s): Samreen-19

Signature 2

Needs review

Curated date: 2024/03/24

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 9

Description: Differential abundance analysis for smoking behaviour

Abundance in Group 1: decreased abundance in Ex

NCBI Quality ControlLinks
Bacteroides ovatus
unclassified Anaerostipes
unclassified Bilophila
unclassified Faecalibacterium
unclassified Oscillospiraceae
unclassified Sutterella
unclassified Citrobacter

Revision editor(s): Samreen-19

Experiment 6


Needs review

Curated date: 2024/03/25

Curator: Samreen-19

Revision editor(s): Samreen-19, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Ex
Group 1 name Corresponds to the case (exposed) group for case-control studies
Yes
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Inflammatory Bowel Disease (IBD) who are smokers
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/25

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 9

Description: Differential abundance analysis for smoking behaviour

Abundance in Group 1: increased abundance in Yes

NCBI Quality ControlLinks
unclassified Bilophila
unclassified Faecalibacterium
unclassified Bacteroides
unclassified Sutterella

Revision editor(s): Samreen-19

Signature 2

Needs review

Curated date: 2024/03/25

Curator: Samreen-19

Revision editor(s): Samreen-19

Source: Appendix Table 9

Description: Differential abundance analysis for smoking behavior

Abundance in Group 1: decreased abundance in Yes

NCBI Quality ControlLinks
Bacteroides ovatus
Phocaeicola dorei
unclassified Anaerostipes
unclassified Bacteroides
unclassified Lachnospiraceae
unclassified Oscillospiraceae
unclassified Parasutterella
unclassified Citrobacter

Revision editor(s): Samreen-19