DIetary plAnt Extracts, Colonic MicrObes, and Apoe geNetics Interactions stuDy

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:

• Online screening, consenting, and collection of basic information
• Collection of a salivary sample in person at the Clinical Research Facility or home and return to the labs via pre-paid postal mail.
• Confirmation of eligibility to donate stool samples.
• Collection of stool samples on the same day as sample collection. Returning the sample in person or through the pre-paid postal system.

Inclusion criteria

• Aged between 18-35 years old or aged 55+ years old
• Fluent in written and spoken English and capacity to consent
• Availability to take part in the study

Exclusion criteria

• Participants will be excluded from donating if they have been diagnosed with any gastrointestinal conditions such as inflammatory bowel disease.
• They will also be excluded if they have a diagnosis of any form of dementia or severe cognitive impairment.
• They currently consume a high flavonoid intake defined as >15 portions of flavonoid rich food per day.
• History or MRI evidence of brain damage, including significant trauma, stroke, learning difficulties or serious neurological disorder, including a loss of consciousness for more than 24 hours.
• Currently smoking or ceased smoking less than 6 months ago.
• Chronic fatigue syndrome, liver disease, diabetes mellitus, or gall bladder abnormalities.
• History of alcohol or drug dependency.
• Clinically diagnosed psychiatric disorder.
• Currently a participant or have been a participant in any other study involving an investigational product within the last 4 weeks.
• Received a COVID-19 diagnosis within the last 30 days