Characterising microbiome and immune system changes in Parkinson’s disease

What is the purpose of this research?

In Parkinson's disease (PD), the brain's immune cells, called microglia, can become persistently activated due to the accumulation of protein clumps called Lewy bodies. This constant immune activation can lead to a cycle of ongoing inflammation in the brain, which can contribute disease progression through the gradual death of brain cells.

Emerging evidence also suggests that in addition to ongoing inflammation in the brain, generalised inflammation, particularly of the gut, can contribute to the progression of the disease. Metabolomics profiling of host and gut microbiome alterations in Parkinson’s disease could therefore provide early insights into the onset and progression of PD and the discovery of harmful microbiome metabolites which are linked to the progression of Parkinson’s disease.

Skin biopsies show deposits of a specific form of protein in the brain and the skin of patients with PD (phosphorylated alpha-synuclein). The deposition of this protein in the skin is emerging as a reliable early biomarker for Parkinson’s disease. A new ultrasensitive assay allows for the rapid detection of very small amounts of aggregates of this protein.

We would like to measure and compare the levels of these microbiome metabolites, species and immune markers in blood, urine, saliva, skin and stool samples of both healthy volunteers and participants with Parkinson’s disease to determine if they can be used in diagnostic assessments of patients, to determine how patients are progressing, and if treatments are effective.

In addition, we aim to generate mice mimicking the gut microbiome of PD patients, by performing faecal microbial transplant (FMT) from humans into gnotobiotic mice. This will enable us to understand how changes in the microbiome can drive the onset and progression of Parkinson’s disease.

Are you looking for people like me?

You can participate in this research if you are:

• a Parkinson’s disease (PD) patient over 30 years of age
• a healthy volunteer over 30 years of age.

And information sheet will be provided that explains what is involved to help you decide if you want to take part in the research. Please read this information carefully. Ask questions about anything that you do not understand or want to know more about.

Before deciding whether or not to take part, you might want to talk about it with a relative, friend, or another member of the clinic staff.

If you decide to take part in this study, we will ask you to complete and sign a consent form. By signing it you are telling us that you:

• understand what you have read
• consent to take part in the research project
• consent to the use of your personal and health information as described.

You will be given a copy of the information sheet and consent form to keep.

What will you ask me to do?

Visit the Translational Research Institute

If you decide to take part, you will need to attend the Translational Research Institute (TRI) Clinical Research Facility (CRF) once for approximately two hours. When you attend the TRI Clinical Research Facility, you will be asked to complete a brief questionnaire which will provide us with information about your age, gender and employment history.  We will ask you some questions about previous exposure to toxins, your Parkinson’s disease (if relevant), previous problems with constipation, your medical history and any medications you’re currently taking.  If you have Parkinson’s disease, we would also like to contact your specialist to confirm a few details about your diagnosis, in order to confirm eligibility for this study. You will also be requested to complete disease–specific assessments by a neurologist or qualified nurse. Please see the table in the information sheet for more details of the assessments.

At this visit, a neurologist or a qualified nurse will collect a single punch skin biopsy. For that, the skin will be made numb with a lidocaine solution injection, then a sterile tool will be used to collect a 3mm cylindrical core of tissue sample. An ointment will be applied to the biopsy site and the biopsy site will be covered with a gelfoam dressing. Properly administered local anaesthesia makes this a painless procedure. Note that the gelfoam dressing is an absorbable powder which contains pork skin gelatin. If you have an allergy or religious beliefs which prevent the use of pork skin gelatin, you can let us know and we can use a different type of dressing (steri-strip or suture).

We will also collect a blood sample of approximately 35 ml (about three tablespoons) and ask you to provide urine and saliva samples. You will be given two stool sample kits to take home with you, along with detailed written instructions on how to collect the stool samples in the comfort of your own home. We will also provide you with another questionnaire to complete on the same day you collect your stool samples. This questionnaire, which should take less than 30 minutes to complete, will ask you about your recent health, whether you’ve had any problems with symptoms of anxiety and depression, and whether you’ve consumed any tobacco, alcohol or caffeine recently. Once you have collected the samples and completed the questionnaire, we will then ask you to return them in the self-addressed packaging which will be provided to you.

Follow-up phone contact (10 minutes)

Two to three business days after the skin biopsy a phone call will be performed to ensure the participant has not experienced any adverse events or has any concerns. This call will also remind the participant that the faecal samples and questionnaires need completing.

Are there any risks for me in taking part?

Risks associated with performing punch biopsies of the skin include pain and bruising at the site where the biopsy is taken. There is a small risk that the biopsy site may change colour. The skin biopsy may leave a tiny scar. There is also a small possibility of infection or bleeding at the biopsy site. Although very rare, it is possible to have an allergic reaction to the local anaesthetic (lidocaine) or betadine.

Standard collection of blood samples may cause pain, bruising, and in rare cases, infection. We advise that you maintain pressure on the site for at least five minutes and do not use the affected arm to lift anything heavy for 24 hours.

There are no expected side-effects from providing the urine or saliva samples, but you could find providing a stool sample to be distasteful. However, it is done in the privacy and convenience of your own home.

Are there any benefits for me in taking part?

You will not benefit directly from participating in this study, but the results of this research will provide valuable information which may help us understand the causes of Parkinson’s disease and potentially develop new diagnostic tests.

Your participation is completely voluntary, and you are free to choose not to participate in this study. Your decision to participate or not to participate will not affect your current standard care or treatment in any way whether you are a patient or a volunteer.

Will I be compensated for my time?

You will not benefit financially from your involvement in this study project although any parking expenses incurred through attending the research clinic will be reimbursed by the study team.

I am interested - what should I do next?

For questions about being a research participant, contact Schible Kurian on telephone 3443 7234 or email schible.kurian@health.qld.gov.au.