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

From BugSigDB
Reviewed Marked as Reviewed by Folakunmi on 2024-1-23
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/08

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Folakunmi

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
Cerebral small vessel disease genetic cerebral small vessel disease,small vessel cerebrovascular disease,Cerebral small vessel 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 0 sample size Number of subjects in the control (unexposed) group
674
Group 1 sample size Number of subjects in the case (exposed) group
108
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).
relative abundances
Statistical test
MaAsLin2
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

Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/14

Curator: Sinmisoluwa Adesanya

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

Source: Table S4, S5, S6

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

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

NCBI Quality ControlLinks
Christensenella
Clostridium ruminantium
Enterocloster aldenensis
Oscillospira
Oscillospira guilliermondii
Erysipelotrichaceae

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

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/14

Curator: Sinmisoluwa Adesanya

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

Source: Table S4, S5, S6

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

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

NCBI Quality ControlLinks
Candidatus Poribacteria
Clostridium
Methanobrevibacter
Victivallis

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

Experiment 2


Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Folakunmi

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 0 sample size Number of subjects in the control (unexposed) group
832
Group 1 sample size Number of subjects in the case (exposed) group
136

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

Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi

Source: Table S4, S5, S6

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

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

NCBI Quality ControlLinks
Christensenella
Enterocloster aldenensis
Pseudomonadota

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi, Welile

Source: Table S4, S5, S6

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

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

NCBI Quality ControlLinks
Actinomycetota
Anaerosinus
Bacillota
Bacteroidia
Barnesiella
Barnesiella intestinihominis
Candidatus Parcubacteria
Catenibacterium
Catenibacterium mitsuokai
Clostridium
Clostridium ruminantium
Lachnotalea glycerini
Methanobrevibacter
Oscillospira
Ruminococcus
[Ruminococcus] lactaris
Erysipelotrichaceae

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi, Welile

Experiment 3


Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Folakunmi

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 0 sample size Number of subjects in the control (unexposed) group
822
Group 1 sample size Number of subjects in the case (exposed) group
121

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

Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi

Source: Table S4, S5, S6

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

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

NCBI Quality ControlLinks
Catenibacterium
Clostridium ruminantium
Collinsella
Collinsella aerofaciens
Enterocloster aldenensis
Enterocloster lavalensis

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-1-23

Curated date: 2023/10/15

Curator: Sinmisoluwa Adesanya

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi

Source: Table S4, S5, S6

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

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

NCBI Quality ControlLinks
Alistipes
Bacillota
Candidatus Parcubacteria
Methanobrevibacter
Ruminococcus
[Ruminococcus] lactaris

Revision editor(s): Sinmisoluwa Adesanya, Chinelsy, Folakunmi