Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study

From BugSigDB
Reviewed Marked as Reviewed by Lwaldron on 2022/03/28
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Stadlbauer V, Engertsberger L, Komarova I, Feldbacher N, Leber B, Pichler G, Fink N, Scarpatetti M, Schippinger W, Schmidt R, Horvath A
Journal
BMC geriatrics
Year
2020
Keywords:
Butyrate producer, Cognitive function, Diversity, Gut barrier, Inflammation, Microbiome
BACKGROUND: Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia. METHODS: To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16S rRNA sequencing, QIIME 2 and Calypso 7.14 tools. RESULTS: Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition. CONCLUSION: Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia. TRIAL REGISTRATION: NCT03167983 .

Experiment 1


Reviewed Marked as Reviewed by Lwaldron on 2022/03/28

Curated date: 2022/03/21

Curator: Maryemzaki

Revision editor(s): WikiWorks, LGeistlinger, Lwaldron, Maryemzaki, Peace Sandy

Subjects

Location of subjects
Austria
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
Dementia dementia,dementia (disease),Dementia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control, mild, and moderate dementia
Group 1 name Corresponds to the case (exposed) group for case-control studies
Severe dementia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
MMSE 0-9: The Mini-Mental State Examination [19] and the clock drawing test [20] were used to quantify cognitive function. We classified cognitive dysfunction according to the German S3-guideline on Dementia 2016 as MMSE 0–9: severe; MMSE 10–19: moderate; MMSE 20–26: mild; MMSE 27–30: no dementia [21].
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

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).
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

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 Lwaldron on 2022/03/28

Curated date: 2022/03/28

Curator: Lwaldron

Revision editor(s): Lwaldron

Source: Figure 4A

Description: 4a Features selected by Linear discriminant analysis Effect Size (LEfSe) to discriminate between dementia different stages of cognitive dysfunction and controls. Right-hand bar showing biomarkers of severe dementia.

Abundance in Group 1: increased abundance in Severe dementia

NCBI Quality ControlLinks
Bacteroides sp.
Bacteroides uniformis
Enterocloster clostridioformis
Eubacterium coprostanoligenes
Anaerotruncus
Eisenbergiella
Enterobacteriaceae
Hungatella
Oscillibacter
Ruthenibacterium lactatiformans
Sellimonas
Sellimonas sp.
Streptococcus salivarius
Syntrophococcus
[Clostridium] leptum
[Eubacterium] nodatum
[Ruminococcus] torques
Streptococcus thermophilus
Actinomycetaceae
Enterobacterales
Actinomycetales
Anaeromassilibacillus sp. Marseille-P3371
Oscillospiraceae bacterium
Faecalibacterium sp. UBA1819

Revision editor(s): Lwaldron

Experiment 2


Reviewed Marked as Reviewed by Lwaldron on 2022/03/28

Curated date: 2022/03/01

Curator: Maryemzaki

Revision editor(s): Lwaldron, Maryemzaki, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Controls without cognitive impairments
Group 1 name Corresponds to the case (exposed) group for case-control studies
Patients with dementia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants with any level of dementia (mild, moderate, severe).
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
23

Lab analysis

Statistical Analysis

Alpha Diversity

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 Lwaldron on 2022/03/28

Curated date: 2022/03/15

Curator: Maryemzaki

Revision editor(s): Lwaldron, Maryemzaki

Source: 3a

Description: Differentially abundant taxa between any level of dementia vs controls

Abundance in Group 1: increased abundance in Patients with dementia

NCBI Quality ControlLinks
Anaerostipes hadrus
Clostridiales bacterium
Enterocloster clostridioformis
Lachnoclostridium
Phocaeicola dorei
[Ruminococcus] torques

Revision editor(s): Lwaldron, Maryemzaki

Signature 2

Reviewed Marked as Reviewed by Lwaldron on 2022/03/28

Curated date: 2022/03/15

Curator: Maryemzaki

Revision editor(s): Lwaldron, Maryemzaki

Source: Figure 3a

Description: Differentially abundant taxa between any level of dementia vs controls

Abundance in Group 1: decreased abundance in Patients with dementia

NCBI Quality ControlLinks
Agathobacter
Agathobacter sp.
Lachnospiraceae bacterium MC_35
Lachnospiraceae bacterium NK4A136
uncultured Erysipelotrichaceae bacterium
uncultured Lachnospiraceae bacterium
uncultured Oscillospiraceae bacterium

Revision editor(s): Lwaldron, Maryemzaki

Experiment 3


Reviewed Marked as Reviewed by Lwaldron on 2022/03/28

Curated date: 2022/03/28

Curator: Lwaldron

Revision editor(s): Lwaldron, LGeistlinger, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
control, mild, and severe dementia
Group 1 name Corresponds to the case (exposed) group for case-control studies
moderate dementia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
MMSE 10-19: The Mini-Mental State Examination [19] and the clock drawing test [20] were used to quantify cognitive function. We classified cognitive dysfunction according to the German S3-guideline on Dementia 2016 as MMSE 0–9: severe; MMSE 10–19: moderate; MMSE 20–26: mild; MMSE 27–30: no dementia [21].
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Alpha Diversity

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 Lwaldron on 2022/03/28

Curated date: 2022/03/28

Curator: Lwaldron

Revision editor(s): Lwaldron

Source: Figure 4A (moderate)

Description: Moderate vs control, mild, and severe dementia

Abundance in Group 1: increased abundance in moderate dementia

NCBI Quality ControlLinks
Lactobacillus amylovorus
Collinsella aerofaciens
Bacteroides sp.
Lactobacillus
Ruminiclostridium
Lactobacillaceae
Lactobacillaceae
Lactobacillales
Bacilli

Revision editor(s): Lwaldron

Experiment 4


Reviewed Marked as Reviewed by Lwaldron on 2022/03/28

Curated date: 2022/03/28

Curator: Lwaldron

Revision editor(s): Lwaldron, LGeistlinger, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
control, moderate, and severe dementia
Group 1 name Corresponds to the case (exposed) group for case-control studies
mild dementia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
MMSE 20-26: The Mini-Mental State Examination [19] and the clock drawing test [20] were used to quantify cognitive function. We classified cognitive dysfunction according to the German S3-guideline on Dementia 2016 as MMSE 0–9: severe; MMSE 10–19: moderate; MMSE 20–26: mild; MMSE 27–30: no dementia [21].

Lab analysis

Statistical Analysis

Alpha Diversity

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 Lwaldron on 2022/03/28

Curated date: 2022/03/28

Curator: Lwaldron

Revision editor(s): Lwaldron

Source: Figure 4A (mild)

Description: These are "biomarkers" of mild dementia that are lower abundance in controls, moderate, and severe dementia.

Abundance in Group 1: increased abundance in mild dementia

NCBI Quality ControlLinks
Faecalibacterium prausnitzii
Faecalibacterium
Fusicatenibacter
Lachnospira eligens

Revision editor(s): Lwaldron