Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model
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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
Chevalier C, Tournier BB, Marizzoni M, Park R, Paquis A, Ceyzériat K, Badina AM, Lathuiliere A, Saleri S, Cillis F, Cattaneo A, Millet P, Frisoni GB
Journal
Genes, brain, and behavior
Year
2025
Keywords:
3xTgAD mice, APOE, Alzheimer, fecal microbiota transplantation (FMT), microbiota, neuroinflammation
Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.
Experiment 1
Needs review
Subjects
- Location of subjects
- Switzerland
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Cecum mucosa Caecum mucosa,Caecum mucosa of organ,Caecum mucous membrane,Caecum organ mucosa,Cecal mucosa,Cecum mucosa of organ,Cecum mucous membrane,Cecum organ mucosa,Intestinum crassum caecum mucosa,Intestinum crassum caecum mucosa of organ,Intestinum crassum caecum mucous membrane,Intestinum crassum caecum organ mucosa,Mucosa of caecum,Mucosa of cecum,Mucosa of intestinum crassum caecum,Mucosa of organ of caecum,Mucosa of organ of cecum,Mucosa of organ of intestinum crassum caecum,Mucous membrane of caecum,Mucous membrane of cecum,Mucous membrane of intestinum crassum caecum,Organ mucosa of caecum,Organ mucosa of cecum,Organ mucosa of intestinum crassum caecum,Cecum mucosa,cecum mucosa
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Untreated Mice- Fecal Microbiota Transplant (Mice-FMT)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Alzheimer's disease(AD) patient (AD-FMT)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This refers to an 80-year-old Alzheimer's disease(AD) patient; with no protection to AD, clinical diagnosis of dementia, brain amyloidosis, APOEε4 carrier genotype, female gender.
- Group 1 sample size Number of subjects in the case (exposed) group
- 1
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-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).
- arcsine square-root
- Statistical test
- MaAsLin2
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.02
- 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
- unchanged
Signature 1
Needs review
Source: Fig. 3C
Description: Differential abundance of genera between the FMT recipient mice
Abundance in Group 1: decreased abundance in Alzheimer's disease(AD) patient (AD-FMT)
Revision editor(s): KateRasheed, WikiWorks
Experiment 2
Needs review
Curated date: 2025/02/13
Curator:
Revision editor(s):
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Apolipoprotein E (APOEe2 allele) - APOEe2-FMT
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- APOEe2 allele (APOEe2-FMT) refers to a cognitively healthy 73-year-old with the protective APOEe2 allele with genetic-related protection to AD (APOEε2 carrier), associated with no cognitive decline diagnosed, no brain amyloidosis, a high level of education, male gender.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Needs review
Source: Fig. 3C
Description: Differential abundance of genera between the FMT recipient mice
Abundance in Group 1: increased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Parabacteroides |
Revision editor(s): KateRasheed, WikiWorks
Signature 2
Needs review
Source: Fig. 3C
Description: Differential abundance of genera between the FMT recipient mice
Abundance in Group 1: decreased abundance in
Revision editor(s): KateRasheed, WikiWorks
Experiment 3
Needs review
Curated date: 2025/02/13
Curator:
Revision editor(s):
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Healthy donor (Young-FMT)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Healthy donor (Young-FMT) refers to a 22-year-old age-related protection to AD, with no APOE gene-related risk (ε3/ε3), no cognitive complaints, male gender.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Fig. 3C
Description: Differential abundance of genera between the FMT recipient mice
Abundance in Group 1: increased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Butyricimonas | ||
| Phascolarctobacterium | ||
| UBA1819UBA1819 |
Revision editor(s): KateRasheed, WikiWorks
Signature 2
Needs review
Source: Fig. 3C
Description: Differential abundance of genera between the FMT recipient mice
Abundance in Group 1: decreased abundance in
Revision editor(s): KateRasheed, WikiWorks
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Alzheimer's disease(AD) patient (AD-FMT)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Apolipoprotein E (APOEe2 allele) - APOEe2-FMT
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- APOEe2 allele (APOEe2-FMT) refers to a cognitively healthy 73-year-old with the protective APOEe2 allele with genetic-related protection to AD (APOEε2 carrier), associated with no cognitive decline diagnosed, no brain amyloidosis, a high level of education, male gender.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 1
Lab analysis
Statistical Analysis
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Fig. 3D
Description: Differential abundance of genera between the FMT recipient mice when compared with AD-FMT
Abundance in Group 1: increased abundance in Apolipoprotein E (APOEe2 allele) - APOEe2-FMT
| NCBI | Quality Control | Links |
|---|---|---|
| Ligilactobacillus | ||
| Bilophila | ||
| Eubacterium coprostanoligenes groupEubacterium coprostanoligenes group | ||
| Parabacteroides | ||
| Prevotellaceae UCG-001Prevotellaceae UCG-001 |
Revision editor(s): KateRasheed, WikiWorks
Signature 2
Needs review
Source: Fig. 3D
Description: Differential abundance of genera between the FMT recipient mice when compared with AD-FMT
Abundance in Group 1: decreased abundance in Apolipoprotein E (APOEe2 allele) - APOEe2-FMT
Revision editor(s): KateRasheed, WikiWorks
Experiment 5
Needs review
Curated date: 2025/02/13
Curator:
Revision editor(s):
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Healthy donor (Young-FMT)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Healthy donor (Young-FMT) refers to a 22-year-old age-related protection to AD, with no APOE gene-related risk (ε3/ε3), no cognitive complaints, male gender.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Needs review
Source: Fig. 3D
Description: Differential abundance of genera between the FMT recipient mice when compared with AD-FMT
Abundance in Group 1: increased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Ligilactobacillus | ||
| Bilophila | ||
| Eubacterium coprostanoligenes groupEubacterium coprostanoligenes group | ||
| Phascolarctobacterium | ||
| Muribaculum | ||
| UBA1819UBA1819 |
Revision editor(s): KateRasheed, WikiWorks
Signature 2
Needs review
Source: Fig. 3D
Description: Differential abundance of genera between the FMT recipient mice when compared with AD-FMT
Abundance in Group 1: decreased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Desulfovibrio | ||
| Lachnospiraceae UCG-006Lachnospiraceae UCG-006 |
Revision editor(s): KateRasheed, WikiWorks
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