Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
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
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
Revision editor(s): Lwaldron
Experiment 2
Reviewed Marked as Reviewed by Lwaldron on 2022/03/28
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
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
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
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 Control | Links |
|---|---|---|
| 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
Source: Figure 3a
Description: Differentially abundant taxa between any level of dementia vs controls
Abundance in Group 1: decreased abundance in Patients with dementia
Revision editor(s): Lwaldron, Maryemzaki
Experiment 3
Reviewed Marked as Reviewed by Lwaldron on 2022/03/28
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
Source: Figure 4A (moderate)
Description: Moderate vs control, mild, and severe dementia
Abundance in Group 1: increased abundance in moderate dementia
| NCBI | Quality Control | Links |
|---|---|---|
| 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
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
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 Control | Links |
|---|---|---|
| Faecalibacterium prausnitzii | ||
| Faecalibacterium | ||
| Fusicatenibacter | ||
| Lachnospira eligens |
Revision editor(s): Lwaldron
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