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| Name | Class |
|---|---|
| Quadram Institute Bioscience | OTHER |
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This study will involve donating a salivary sample and a faecal (stool) sample. These will be analysed in the laboratory to determine the forms of the APOE gene you are carrying (your APOE genotype) and the response of the bacteria in your colon to reactive compounds extracted from edible plants (dietary bioactives).
In an ageing population, the incidence of dementia is rapidly increasing and poses a significant financial, societal, and above all, personal burden. Aside from ageing, the type of APOE gene an individual carries (their APOE genotype) is the greatest risk factor for the development of cognitive decline. It has been shown that the APOE genotype of an individual influences the types of bacteria present in the colon. The bacteria which reside in the colon have recently emerged as a significant contributor to nutrition and health and have been suggested to influence brain functioning through complex connections between the gut and the brain.
Nutrition is considered important for brain function throughout life, and findings from recent laboratory and human observational studies have suggested that reactive compounds extracted from edible plants (dietary bioactives) can not only improve brain function, but they can change the function and composition of gut bacteria. Dietary bioactives are a range of natural compounds found in great concentrations within fruits and vegetables which influence the body. An example of a dietary bioactive is a group of compounds known as polyphenols. These polyphenols are described as antioxidants and are found in various foods, including berries, tea, and cocoa.
There have been no previous studies looking at the impact of dietary bioactives on the microbiome of each APOE genotype and the metabolites produced by each of these bacteria. We aim with the current study to identify how dietary bioactives from a range of plant tissue could influence gut bacteria present and the metabolites produced by the bacteria in each APOE group, and the compounds produced by these bacteria.
What will the study involve? Once we have established a potentially suitable participant, they will be sent a salivary sampling kit. Depending on the genotype, age and sex, participants will be requested to donate a stool sample. The stool will be processed in a colon model with cocoa polyphenol added.
The study involves the following stages:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prospectively genotyped participants | These participants will be advertised to in the local area. They will be genotyped for their APOE genotype, and then the stool sample will be collected. | ||
| Database participants | Participants from the previously genotyped cohort "Early sleep and circadian markers of Alzheimer's disease: the impact of APOE-ε4 on circadian rhythm and sleep-wake homeostasis in humans" (Reference: 2017/18-135) who have consented to be contacted will be contacted to collect a stool sample. |
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| Measure | Description | Time Frame |
|---|---|---|
| Whether there is a significant difference between the in vitro metabolism of flavan-3-ols using a human colon model | Participants will be genotyped for their APOE genotype. They will then be requested to donate a stool sample. This stool sample will be run through a colon.model inoculated with flavan-3-ols to determine whether there is a significant difference between the genotypes. Flavan-3-ol metabolism will be measured with LCMS | 09/2025 |
| Determine whether there are significant differences between the composition of the gut microbiome of each APOE genotype. | Participants will be genotyped for their APOE genotype. Their stool sample will then have its gut microbiome analysed. Metagenomic techniques will be utilised to analyse the microbiome | 09/2025 |
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Inclusion Criteria:
Exclusion Criteria:
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Healthy adults who fit the above inclusion and exclusion criteria. Able to donate a stool and salivary sample.
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| Name | Affiliation | Role |
|---|---|---|
| David Vauzour, PhD | University of East Anglia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Norwich and Norfolk University Hospital Clinical Research Facility | Norwich | Norfolk | NR4 7UY | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36348357 | Background | Raulin AC, Doss SV, Trottier ZA, Ikezu TC, Bu G, Liu CC. ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies. Mol Neurodegener. 2022 Nov 8;17(1):72. doi: 10.1186/s13024-022-00574-4. | |
| 30958695 | Result | Tran TTT, Corsini S, Kellingray L, Hegarty C, Le Gall G, Narbad A, Muller M, Tejera N, O'Toole PW, Minihane AM, Vauzour D. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology. FASEB J. 2019 Jul;33(7):8221-8231. doi: 10.1096/fj.201900071R. Epub 2019 Apr 8. |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Salivary sample Stool sample
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |