Gut microbiome signatures reflect different subtypes of irritable bowel syndrome

From BugSigDB
Reviewed Marked as Reviewed by Folakunmi on 2024-2-6
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Su Q, Tun HM, Liu Q, Yeoh YK, Mak JWY, Chan FK, Ng SC
Journal
Gut microbes
Year
2023
Keywords:
Irritable bowel syndrome, depression, diet, gut microbiome, subtype
Irritable bowel syndrome (IBS) is a heterogeneous condition with multifactorial pathogenesis. We studied deeply phenotyped individuals with microbiota sequencing enrolled in the American Gut Project. The IBS subjects were matched by age, gender, body mass index, geography, and dietary patterns with non-IBS controls. A total of 942 subjects with IBS-Diarrhea (IBS-D), IBS-Constipation (IBS-C), unclassified IBS (IBS-U), and 942 non-IBS controls were included. We compared taxonomic and functional composition of gut microbiota based on 16S sequencing data and linked them with clinical characteristics and dietary factors. Subjects with IBS-D or IBS-U but not IBS-C showed significantly reduced bacterial diversity (Shannon; p < .01). Distinct bacterial signatures were associated with different IBS subtypes, and the related functional changes were related to IBS pathogenesis, such as the increased hydrogen sulfide production pathway in IBS-D and the increased palmitoleate biosynthesis pathway in IBS-C. IBS subjects with depression showed lower abundance of Bifidobacterium, Sutterella, Butyricimonas and higher abundance of Proteus than those without depression. The relative abundance of microbial short-chain fatty acid production pathways was significantly lower in IBS patients with depression than those without depression in all three subtypes. Female, younger age in IBS-D, and older age in IBS-C were associated with more severe microbiota dysbiosis, and distinct dietary factors had significant effects on the gut microbiota in different IBS subtypes. Our analysis identified the compositional uniqueness of gut microbiota in different IBS subtypes. Distinct associations of the gut microbiota with depression in IBS provide insights into shared pathways in disease pathogenesis. These findings highlight the importance of personalized gut microbiome modulation approaches in different subtypes for optimal therapeutic effects.

Experiment 1


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/25

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Subjects

Location of subjects
United Kingdom
United States of America
Canada
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
Irritable bowel syndrome [X]Psychogenic IBS,Adaptive colitis,Colitides, Mucous,Colitis, Mucous,Colon spasm,Colon, Irritable,Functional bowel disease,IBD,IBS,IBS - Irritable bowel syndrome,IC - Irritable colon,Irritable bowel,Irritable bowel - IBS,irritable bowel syndrome,Irritable Bowel Syndromes,Irritable Colon,irritable colon,Irritable colon (disorder),Irritable colon - Irritable bowel syndrome,Irritable colon syndrome,Membranous colitis,Mucous Colitides,Mucous colitis,mucus colitis,Nervous colitis,Psychogenic IBS,psychogenic IBS,Spastic colitis,Spastic colon,spastic colon,Syndrome, Irritable Bowel,Syndromes, Irritable Bowel,Irritable bowel syndrome
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-IBS1 (Non-irritable bowel syndrome 1)
Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS-C (IBS-Constipation)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with IBS-C, a subtype of IBS characterized by constipation (difficulty passing stool)
Group 0 sample size Number of subjects in the control (unexposed) group
180
Group 1 sample size Number of subjects in the case (exposed) group
180
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
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)?
No
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, alcohol drinking, body mass index, diet, geographic area, sex
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, alcohol drinking, diet, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/25

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Figure 2a, b and c and Supplemental. Table 3

Description: Differential microbial abundance between IBS-C and Non-IBS1

Abundance in Group 1: decreased abundance in IBS-C (IBS-Constipation)

NCBI Quality ControlLinks
Actinomycetota
Agathobacter
Anaerobutyricum hallii
Anaerosporobacter
Anaerostipes
Bacillota
Bifidobacterium
Blautia
Butyricicoccus
Coprococcus
Corynebacterium
Dorea
Eubacterium ruminantium
Eubacterium ventriosum
Eubacterium xylanophilum
Faecalibacterium
Fusicatenibacter
Haemophilus
Lachnospira
Lachnospira eligens
Lachnospiraceae bacterium NK4A136
Monoglobus
Prevotella
Roseburia
Ruminococcus
Ruminococcus gauvreauii
Subdoligranulum
Succinivibrio
Sutterella
Veillonella
[Eubacterium] siraeum
bacterium FCS020
uncultured Erysipelotrichaceae bacterium
uncultured Lachnospiraceae bacterium
uncultured Oscillospiraceae bacterium
Lachnospiraceae_CAG_56Lachnospiraceae_CAG_56
bacterium ND3007

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi, Joan Chuks

Source: Figure 2a, b and c and Supplemental Table 3

Description: Differential microbial abundance between IBS-C and Non-IBS1

Abundance in Group 1: increased abundance in IBS-C (IBS-Constipation)

NCBI Quality ControlLinks
Akkermansia
Barnesiella
Christensenella
Clostridia incertae sedis
Clostridiales Family XIII bacterium
Delftia
Desulfovibrio
Dielma
Eisenbergiella
Escherichia/Shigella sp.
Eubacterium
Faecalitalea
Finegoldia
Flavonifractor
Frisingicoccus
Hungatella
Hydrogenoanaerobacterium
Intestinimonas
Negativibacillus
Oscillibacter
Oscillospira
Parabacteroides
Ruminiclostridium
Thermodesulfobacteriota
[Clostridium] innocuum
Ruminococcaceae_UBA1819Ruminococcaceae_UBA1819
Incertae sedis DTU014Incertae sedis DTU014
Diplocloster

Revision editor(s): ChiomaBlessing, Folakunmi, Joan Chuks

Experiment 2


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-IBS2 (Non-irritable bowel syndrome 2)
Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS-D (IBS-Diarrhea)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with IBS-D, a subtype of IBS characterized by diarrhea (watery stool)
Group 0 sample size Number of subjects in the control (unexposed) group
302
Group 1 sample size Number of subjects in the case (exposed) group
302

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Figure 2a, b and c and Supplemental. Table 4

Description: Differential microbial abundance between IBS-D and Non-IBS2

Abundance in Group 1: decreased abundance in IBS-D (IBS-Diarrhea)

NCBI Quality ControlLinks
Achromobacter
Akkermansia
Alistipes
Anaerostipes
Barnesiella
Bifidobacterium
Butyricimonas
Butyrivibrio
Campylobacter
Candidatus Izemoplasmatales
Christensenellaceae
Clostridiales Family XIII bacterium
Coprococcus
Cyanobacteriota
Dechloromonas
Desulfovibrio
Eubacterium ruminantium
Eubacterium xylanophilum
Faecalibacterium
Fenollaria
Hydrogenoanaerobacterium
Lentisphaerota
Muribaculaceae
Odoribacter
Oxalobacter
Parasutterella
Peptoniphilus
Porphyromonas
Prevotella
Ruminococcus
Sutterella
Varibaculum
Veillonella
Victivallis
[Eubacterium] siraeum
bacterium ND3007
candidate division VadinBE97
uncultured Erysipelotrichaceae bacterium
uncultured Lachnospiraceae bacterium
uncultured Oscillospiraceae bacterium
Bacilli_RF39Bacilli_RF39
Oscillospiraceae_NK4A21Oscillospiraceae_NK4A21
Incertae sedis DTU014Incertae sedis DTU014
Clostridia_vadinBB60Clostridia_vadinBB60
uncultured Clostridia bacterium

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Iram jamshed, Folakunmi

Source: Figure 2a, b and c and Supplemental Table 4

Description: Differential microbial abundance between IBS-D and Non-IBS2

Abundance in Group 1: increased abundance in IBS-D (IBS-Diarrhea)

NCBI Quality ControlLinks
Abiotrophia
Dorea
Escherichia/Shigella sp.
Flavonifractor
Haemophilus
Mediterraneibacter gnavus
Subdoligranulum
Anaerobutyricum hallii
Brevundimonas
unclassified Defluviitaleaceae

Revision editor(s): ChiomaBlessing, Iram jamshed, Folakunmi

Experiment 3


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-IBS3 (Non-irritable bowel syndrome 3)
Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS-U (IBS-Unclassified)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with IBS-U, a distinct category characterized by normal formed stool
Group 0 sample size Number of subjects in the control (unexposed) group
460
Group 1 sample size Number of subjects in the case (exposed) group
460

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Source: Figure 2a, b and c and Supplemental. Table 5

Description: Differential microbial abundance between IBS-U and Non-IBS3

Abundance in Group 1: decreased abundance in IBS-U (IBS-Unclassified)

NCBI Quality ControlLinks
Agathobacter
Anaerobutyricum hallii
Anaerostipes
Bifidobacterium
Blautia
Campylobacter
Catenibacterium
Collinsella
Dorea
Eubacterium ruminantium
Faecalibacterium
Fenollaria
Finegoldia
Fusicatenibacter
Gemella
Holdemanella
Peptoniphilus
Prevotella
Ruminococcus
Subdoligranulum
Sutterella
Turicibacter
Varibaculum
candidate division VadinBE97
uncultured Erysipelotrichia bacterium
uncultured Lachnospiraceae bacterium
Enterococcus

Revision editor(s): ChiomaBlessing, Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Source: IBS-U (IBS-Unclassified)

Description: Differential microbial abundance between IBS-U and Non-IBS3

Abundance in Group 1: increased abundance in IBS-U (IBS-Unclassified)

NCBI Quality ControlLinks
Escherichia/Shigella sp.
Pseudomonas
Succiniclasticum
[Ruminococcus] torques
Pseudomonadota

Revision editor(s): ChiomaBlessing, Folakunmi

Experiment 4


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Differences from previous experiment shown

Subjects

Location of subjects
Canada
United Kingdom
United States of America


Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Depressive disorder depression,melancholia,melancholias,mental depression,syndrome, depressive,syndromes, depressive,Depressive disorder,depressive disorder
Group 0 name Corresponds to the control (unexposed) group for case-control studies
IBS patients without depression
Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS patients with depression in all three subtypes (IBS-D, IBS-C and IBS-U)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
IBS patients with depression in all three subtypes (IBS-D, IBS-C and IBS-U)
Group 0 sample size Number of subjects in the control (unexposed) group
134
Group 1 sample size Number of subjects in the case (exposed) group
134

Lab analysis

Statistical Analysis

Statistical test
MaAsLin2
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/26

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Atrayees

Source: Figure 3C, Results (text)

Description: Differential microbial abundance between IBS patients with depression in all three subtypes (IBS-D, IBS-C and IBS-U) and IBS patients without depression

Abundance in Group 1: decreased abundance in IBS patients with depression in all three subtypes (IBS-D, IBS-C and IBS-U)

NCBI Quality ControlLinks
Bifidobacterium
Butyricimonas
Sutterella
Butyricicoccaceae

Revision editor(s): ChiomaBlessing, Atrayees

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Figure 3C, Results (text)

Description: Differential microbial abundance between IBS patients with depression in all three subtypes (IBS-D, IBS-C and IBS-U) and IBS patients without depression

Abundance in Group 1: increased abundance in IBS patients with depression in all three subtypes (IBS-D, IBS-C and IBS-U)

NCBI Quality ControlLinks
Proteus

Revision editor(s): ChiomaBlessing

Experiment 5


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Differences from previous experiment shown

Subjects

Location of subjects
United Kingdom
United States of America
Canada


Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Irritable bowel syndrome [X]Psychogenic IBS,Adaptive colitis,Colitides, Mucous,Colitis, Mucous,Colon spasm,Colon, Irritable,Functional bowel disease,IBD,IBS,IBS - Irritable bowel syndrome,IC - Irritable colon,Irritable bowel,Irritable bowel - IBS,irritable bowel syndrome,Irritable Bowel Syndromes,Irritable Colon,irritable colon,Irritable colon (disorder),Irritable colon - Irritable bowel syndrome,Irritable colon syndrome,Membranous colitis,Mucous Colitides,Mucous colitis,mucus colitis,Nervous colitis,Psychogenic IBS,psychogenic IBS,Spastic colitis,Spastic colon,spastic colon,Syndrome, Irritable Bowel,Syndromes, Irritable Bowel,Irritable bowel syndrome
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-IBS (Non-irritable bowel syndrome)
Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS-C (IBS-Constipation) Validation Cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with IBS-C, a subtype of IBS characterized by constipation (difficulty passing stool) in the Validation Cohort
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
44

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental. Figure 5C

Description: Differential microbial abundance between IBS-C and Non-IBS (Validation cohort)

Abundance in Group 1: decreased abundance in IBS-C (IBS-Constipation) Validation Cohort

NCBI Quality ControlLinks
Bacillota
Actinomycetota

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental Figure 5C

Description: Differential microbial abundance between IBS-C and Non-IBS (Validation cohort)

Abundance in Group 1: increased abundance in IBS-C (IBS-Constipation) Validation Cohort

NCBI Quality ControlLinks
Verrucomicrobiota

Revision editor(s): ChiomaBlessing

Experiment 6


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS-D (IBS-Diarrhea) Validation Cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with IBS-D, a subtype of IBS characterized by diarrhea (watery stool) in the Validation Cohort
Group 0 sample size Number of subjects in the control (unexposed) group
48
Group 1 sample size Number of subjects in the case (exposed) group
48

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental Figure 5C

Description: Differential microbial abundance between IBS-D and Non-IBS (Validation cohort)

Abundance in Group 1: decreased abundance in IBS-D (IBS-Diarrhea) Validation Cohort

NCBI Quality ControlLinks
Actinomycetota
Bacillota
Campylobacterota

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental Figure 5C

Description: Differential microbial abundance between IBS-D and Non-IBS (Validation cohort)

Abundance in Group 1: increased abundance in IBS-D (IBS-Diarrhea) Validation Cohort

NCBI Quality ControlLinks
Pseudomonadota

Revision editor(s): ChiomaBlessing

Experiment 7


Reviewed Marked as Reviewed by Folakunmi on 2024-2-6

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Folakunmi

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS-U (IBS-Unclassified) Validation Cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with IBS-U, a distinct category characterized by normal formed stool in the Validation Cohort
Group 0 sample size Number of subjects in the control (unexposed) group
61
Group 1 sample size Number of subjects in the case (exposed) group
61

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental Figure 5C

Description: Differential microbial abundance between IBS-U and Non-IBS (Validation cohort)

Abundance in Group 1: decreased abundance in IBS-U (IBS-Unclassified) Validation Cohort

NCBI Quality ControlLinks
Bacillota
Actinomycetota

Revision editor(s): ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-2-5

Curated date: 2023/10/27

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Source: Supplemental Figure 5C

Description: Differential microbial abundance between IBS-U and Non-IBS (Validation cohort)

Abundance in Group 1: increased abundance in IBS-U (IBS-Unclassified) Validation Cohort

NCBI Quality ControlLinks
Pseudomonadota

Revision editor(s): ChiomaBlessing