Cerebral small vessel disease burden is associated with decreased abundance of gut Barnesiella intestinihominis bacterium in the Framingham Heart Study

Study information

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study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

37604954

DOI Digital object identifier for electronic documents.

https://doi.org/10.1038/s41598-023-40872-5

URI

Authors

Fongang B, Satizabal C, Kautz TF, Wadop YN, Muhammad JAS, Vasquez E, Mathews J, Gireud-Goss M, Saklad AR, Himali J, Beiser A, Cavazos JE, Mahaney MC, Maestre G, DeCarli C, Shipp EL, Vasan RS, Seshadri S

Journal

Scientific reports

Year

2023

A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p values < 0.001), as well as better executive function (p values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and β-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.

Experiment 1

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Curated date: 2023/10/08

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya

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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

cerebral small vessel disease genetic cerebral small vessel disease,small vessel cerebrovascular disease,cerebral small vessel disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Lower burden (Healthy)

Group 1 name Corresponds to the case (exposed) group for case-control studies

High burden (Unhealthy)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Participants with Cerebral small vessel disease that were tested using the PSMD marker

Group 1 sample size Number of subjects in the case (exposed) group

782

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

unspecified

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).

raw counts

Statistical test

PERMANOVA

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

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

age, body mass index, time, education level, sex

Alpha Diversity

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

unchanged

Chao1 Abundance-based estimator of species richness

unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness

unchanged

Signature 1

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Needs review

Curated date: 2023/10/14

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Peace Sandy

Source: Table S4

Description: Difference between the gut microbiome of patients with cSVD marker PSMD and the Lower burden (Healthy) group at phylum rank by PERMANOVA

Abundance in Group 1: increased abundance in High burden (Unhealthy)

NCBI	Quality Control	Links
Candidatus Parcubacteria

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Peace Sandy

Signature 2

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Curated date: 2023/10/14

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Peace Sandy

Source: Table S4

Description: Difference between the gut microbiome of patients with cSVD marker PSMD and the Lower burden (Healthy) group at phylum rank by PERMANOVA

Abundance in Group 1: decreased abundance in High burden (Unhealthy)

NCBI	Quality Control	Links
Candidatus Poribacteria

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Peace Sandy

Experiment 2

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Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Participants with Cerebral small vessel disease that were tested using the WMH marker

Group 1 sample size Number of subjects in the case (exposed) group

968

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

Simpson Estimator of species richness and species evenness: more weight on species evenness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Source: Table S4

Description: Difference between the gut microbiome of patients with cSVD marker WMH and the Lower burden (Healthy) group at phylum rank by PERMANOVA

Abundance in Group 1: increased abundance in High burden (Unhealthy)

NCBI	Quality Control	Links
Candidatus Parcubacteria
Pseudomonadota

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Source: Table S4

Description: Difference between the gut microbiome of patients with cSVD marker WMH and the Lower burden (Healthy) group at phylum rank by PERMANOVA

Abundance in Group 1: decreased abundance in High burden (Unhealthy)

NCBI	Quality Control	Links
Candidatus Parcubacteria
Bacillota
Bacteroidia
Actinomycetota

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Experiment 3

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Needs review

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Participants with Cerebral small vessel disease that were tested using the EF marker

Group 1 sample size Number of subjects in the case (exposed) group

943

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

Simpson Estimator of species richness and species evenness: more weight on species evenness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Source: Table S4

Description: Difference between the gut microbiome of patients with cSVD marker EF and the Lower burden (Healthy) group at phylum rank by PERMANOVA

Abundance in Group 1: increased abundance in High burden (Unhealthy)

NCBI	Quality Control	Links
Candidatus Parcubacteria

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy

Source: Table S4

Description: Difference between the gut microbiome of patients with cSVD marker EF and the Lower burden (Healthy) group at phylum rank by PERMANOVA

Abundance in Group 1: decreased abundance in High burden (Unhealthy)

NCBI	Quality Control	Links
Candidatus Parcubacteria
Bacillota

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy