Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Labus JS, Hollister EB, Jacobs J, Kirbach K, Oezguen N, Gupta A, Acosta J, Luna RA, Aagaard K, Versalovic J, Savidge T, Hsiao E, Tillisch K, Mayer EA
Journal
Microbiome
Year
2017
Keywords:
Bacteroidetes, Brain-gut-microbiome axis, Firmicutes, Irritable bowel syndrome, Metagenome
BACKGROUND: Preclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS. METHODS: Behavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions. RESULTS: Using unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory- and salience-related regions, and with a history of early life trauma. CONCLUSIONS: The results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.

Experiment 1


Needs review

Curated date: 2025/04/24

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp, UtibeIta

Subjects

Location of subjects
United States of America
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
HC (Healthy Control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS1 (Irritable Bowel Syndrome 1)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A subgroup of irritable bowel syndrome (IBS) patients with microbial profiles distinct from healthy control (HC) subjects
Group 0 sample size Number of subjects in the control (unexposed) group
23
Group 1 sample size Number of subjects in the case (exposed) group
13
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
V3-V5
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
Kruskall-Wallis
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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Results text (Figure 4C - F)

Description: The mean relative abundance for identifiable taxa demonstrating overall group differences at each taxonomic level (phylum, class, order, family, and genus)

Abundance in Group 1: increased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacilli
Bacillota
Clostridia
Holdemania
Lactobacillales

Revision editor(s): Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Results text (Figure 4C - F)

Description: The mean relative abundance for identifiable taxa demonstrating overall group differences at each taxonomic level (phylum, class, order, family, and genus)

Abundance in Group 1: decreased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacteroidales
Bacteroidia
Bacteroidota
Parabacteroides

Revision editor(s): Anne-mariesharp

Experiment 2


Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp, UtibeIta

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
HC-like IBS(Healthy Control like Irritable Bowel Syndrome)
Group 0 sample size Number of subjects in the control (unexposed) group
16

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Results text (Figure 4C - F)

Description: The mean relative abundance for identifiable taxa demonstrating overall group differences at each taxonomic level (phylum, class, order, family, and genus)

Abundance in Group 1: increased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacilli
Holdemania
Lactobacillales

Revision editor(s): Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Results text (Figure 4C - F)

Description: The mean relative abundance for identifiable taxa demonstrating overall group differences at each taxonomic level (phylum, class, order, family, and genus)

Abundance in Group 1: decreased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Abiotrophia
Bacteroidales
Bacteroidia
Bacteroidota
Parabacteroides

Revision editor(s): Anne-mariesharp

Experiment 3


Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp, UtibeIta

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
HC (Healthy Control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
HC-like IBS (Healthy Control like Irritable Bowel Syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A subgroup of irritable bowel syndrome (IBS) patients with similar microbial composition as healthy control (HC) subjects
Group 0 sample size Number of subjects in the control (unexposed) group
23
Group 1 sample size Number of subjects in the case (exposed) group
16

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
unchanged
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Results text (Figure 4C - F)

Description: The mean relative abundance for identifiable taxa demonstrating overall group differences at each taxonomic level (phylum, class, order, family, and genus)

Abundance in Group 1: increased abundance in HC-like IBS (Healthy Control like Irritable Bowel Syndrome)

NCBI Quality ControlLinks
Bacillota
Clostridia
Parabacteroides

Revision editor(s): Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/04/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Results text (Figure 4C - F)

Description: The mean relative abundance for identifiable taxa demonstrating overall group differences at each taxonomic level (phylum, class, order, family, and genus)

Abundance in Group 1: decreased abundance in HC-like IBS (Healthy Control like Irritable Bowel Syndrome)

NCBI Quality ControlLinks
Bacteroidales
Bacteroidia
Bacteroidota

Revision editor(s): Anne-mariesharp

Experiment 4


Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
IBS1 (Irritable Bowel Syndrome 1)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A subgroup of irritable bowel syndrome (IBS) patients with microbial profiles distinct from healthy control (HC) subjects
Group 1 sample size Number of subjects in the case (exposed) group
13

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Anne-mariesharp

Source: Table S5

Description: Relative abundance of operational taxonomic units and taxa showing significant group differences

Abundance in Group 1: increased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacilli
Bacillota
Clostridia
Holdemania
Lactobacillales
unclassified Bacillota
unclassified Bacteria
unclassified Clostridia
unclassified Holdemania
unclassified Lachnospiraceae
unclassified Peptostreptococcaceae
unclassified Streptococcus

Revision editor(s): UtibeIta, Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Anne-mariesharp

Source: Table S5

Description: Relative abundance of operational taxonomic units and taxa showing significant group differences

Abundance in Group 1: decreased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacteroidales
Bacteroidia
Bacteroidota
Parabacteroides
Parabacteroides distasonis

Revision editor(s): UtibeIta, Anne-mariesharp

Experiment 5


Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
HC-like IBS(Healthy Control like Irritable Bowel Syndrome)
Group 0 sample size Number of subjects in the control (unexposed) group
16

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Anne-mariesharp

Source: Table S5

Description: Relative abundance of operational taxonomic units and taxa showing significant group differences

Abundance in Group 1: increased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacilli
Bacillota
Clostridia
Holdemania
Lactobacillales
unclassified Bacillota
unclassified Bacteria
unclassified Clostridia
unclassified Holdemania
unclassified Lachnospiraceae
unclassified Peptostreptococcaceae
unclassified Streptococcus

Revision editor(s): UtibeIta, Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Anne-mariesharp

Source: Table S5

Description: Relative abundance of operational taxonomic units and taxa showing significant group differences

Abundance in Group 1: decreased abundance in IBS1 (Irritable Bowel Syndrome 1)

NCBI Quality ControlLinks
Bacteroidales
Bacteroidia
Bacteroidota
Parabacteroides
Parabacteroides distasonis

Revision editor(s): UtibeIta, Anne-mariesharp

Experiment 6


Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
HC (Healthy Control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
HC-like IBS (Healthy Control like Irritable Bowel Syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
A subgroup of irritable bowel syndrome (IBS) patients with similar microbial composition as healthy control (HC) subjects
Group 0 sample size Number of subjects in the control (unexposed) group
23
Group 1 sample size Number of subjects in the case (exposed) group
16

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
unchanged
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Anne-mariesharp

Source: Table S5

Description: Relative abundance of operational taxonomic units and taxa showing significant group differences

Abundance in Group 1: increased abundance in HC-like IBS (Healthy Control like Irritable Bowel Syndrome)

NCBI Quality ControlLinks
Bacillota
Clostridia
Parabacteroides
Parabacteroides distasonis
unclassified Clostridia

Revision editor(s): UtibeIta, Anne-mariesharp

Signature 2

Needs review

Curated date: 2025/04/27

Curator: UtibeIta

Revision editor(s): UtibeIta, Anne-mariesharp

Source: Table S5

Description: Relative abundance of operational taxonomic units and taxa showing significant group differences

Abundance in Group 1: decreased abundance in HC-like IBS (Healthy Control like Irritable Bowel Syndrome)

NCBI Quality ControlLinks
Bacilli
Bacteroidales
Bacteroidia
Bacteroidota
Lactobacillales
unclassified Bacillota
unclassified Peptostreptococcaceae

Revision editor(s): UtibeIta, Anne-mariesharp