Gut microbiome analysis may help detect Parkinson’s before symptoms appear

Analysis of microbes in the gut can reveal whether a person faces an elevated risk of Parkinson's disease, before they have developed any symptoms, suggests a new study led by University College London (UCL) researchers.

The scientists found that people with Parkinson's disease have a distinctive makeup of gut microbes, as do healthy individuals who are genetically at risk of Parkinson's disease, they report in the new Nature Medicine study.

The researchers say their findings could help in developing tests to reveal a person's risk of developing Parkinson's disease, so that they can be offered early support, and potentially also lead to new ways to prevent Parkinson's by targeting the gut.

Professor Anthony Schapira (UCL Queen Square Institute of Neurology), lead investigator of the study said: "Parkinson's disease is a major cause of disability worldwide, and the fastest growing neurodegenerative disease in terms of prevalence and mortality. There is an urgent need to develop treatments that can stop or slow the disease's progression.

"To enable both the research and eventual use of such treatments, we need to develop the means for very early detection of people who will, or likely will, go on to develop the disease.

"In recent years there has been a growing recognition of the links between Parkinson's disease – a brain disorder – and gut health. Here we have strengthened that evidence and shown that microbes in the gut can reveal signs of Parkinson's and may be an early warning signal of Parkinson's risk years before symptom onset."

For the study, the international team led by scientists at UCL and in collaboration with INRAE (Institut national de la recherche agronomique, in France) used an innovative new method to analyse clinical and fecal data from study participants in the UK (at the Royal Free Hospital, London) and Italy. This included 271 people with Parkinson's disease, 43 carriers of the GBA1 variant (a gene variant that can increase the risk of Parkinson's disease by up to 30-fold) with no clinical symptoms, and 150 healthy control participants (as a comparison group).

The scientists found that over a quarter of the microbes making up the gut microbiome (the assortment of microorganisms such as bacteria that live in our digestive tract) – 176 different species – differed in their abundance when comparing people with Parkinson's disease and the healthy control participants. Some microbes were more common among those with Parkinson's disease, while others were more common among healthy study participants. This pattern was most noticeable among people in more advanced stages of Parkinson's.

Most of these microbes (142 species) also consistently differed in abundance when comparing healthy controls to people with the GBA1 gene variant who have not yet experienced any symptoms of Parkinson's disease.

The researchers say that the makeup of the gut microbiome in people who are genetically at risk of Parkinson's, but without any symptoms, resembled an intermediate pattern between the healthy individuals and those with Parkinson's.

Professor Schapira added: "For the first time we identify bacteria in the gut of people with Parkinson's that can also be found in those with a genetic risk for the disease, but before they develop symptoms. Importantly, these same changes can be found in a small proportion of the general population that may put them at increased risk for Parkinson's.

"This discovery opens the way not only to see if the bacteria are a way to identify those at risk of Parkinson's, but also to see if changing the bacterial population, through dietary changes or medication, can reduce a person's risk for Parkinson's."

The scientists corroborated their findings by comparing their results to additional cohort of people in the UK, Korea and Turkey, totalling an additional 638 people with Parkinson's disease and 319 healthy control participants.

A small proportion of the healthy control participants also had gut microbiomes similar to those at risk of Parkinson's disease, raising the question of whether they might also be at risk of Parkinson's. More research is still needed to understand what other genetic or environmental factors are at play to determine whether someone develops Parkinson's.

Study participants also provided data about their dietary habits, which revealed some evidence that those with a more balanced and varied diet are less likely to have gut microbiomes that suggest an elevated risk of Parkinson's; the researchers say this may suggest that diet modification could play a role in Parkinson's prevention.

Co-lead author Professor Stanislav Dusko Ehrlich, honorary professor at the UCL Queen Square Institute of Neurology, said: "Gut microbiome analysis can enable us to identify individuals who are at risk of developing Parkinson's disease, so that we can suggest ways for them to reduce their own risk, such as through dietary adjustments."

Another recent study led by UCL researchers revealed how Parkinson's spreads from the gut to the brain with the help of immune cells, in a finding that might point to potential therapeutic strategies. UCL researchers are also leading the first phase 3 genetically stratified Parkinson's trial that's testing a common cough medicine as a potential treatment, and the world's largest-ever clinical trial of treatments to slow or stop Parkinson's progression, in a study that will be updated as new drugs are developed.

The study was supported by the Michael J. Fox Foundation for Parkinson's Research and the Medical Research Council.