Summary: The fastest-growing neurodegenerative disease in the world may soon be detectable through a simple fecal sample. Researchers have identified a distinctive “microbial signature” in the gut that appears long before the motor tremors of Parkinson’s disease begin.
By studying healthy individuals with a high-risk genetic variant (GBA1), the team discovered that their gut microbiome already resembles an “intermediate” stage of Parkinson’s, suggesting the gut is an early battlefield for the disease.
Key Findings
- Early Detection: Gut microbes provide a “warning signal” years before traditional symptoms like tremors or stiffness appear.
- Universal Results: The findings were corroborated across cohorts in the UK, Korea, and Turkey, totaling over 1,400 participants, proving the microbial signature is consistent across different cultures and diets.
- New Research Avenues: UCL is currently leading trials testing whether targeting these pathways, including using common cough medicines, can slow the disease’s progression.
Source: UCL
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.
Funding: The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Medical Research Council.
Key Questions Answered:
A: No. It means you may have an elevated risk. The microbiome is one piece of a complex puzzle that includes genetics and environment. However, this test allows doctors to monitor at-risk people much earlier than ever before.
A: The study found that people with a varied and balanced diet had “healthier” gut profiles. Increasing fiber, fermented foods, and a diverse range of plants is generally the best way to support a microbiome that resists these disease-linked patterns.
A: Many researchers believe the toxic proteins associated with Parkinson’s (alpha-synuclein) may actually form in the gut’s nervous system first and “climb” up the vagus nerve to the brain over several years.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this Parkinson’s disease research news
Author: Chris Lane
Source: UCL
Contact: Chris Lane – UCL
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Microbiome signature of Parkinson’s disease in healthy and genetically at-risk individuals” by Elisa Menozzi, Yani Ren, Mallia Geiger, Jane Macnaughtan, Micol Avenali, Marco Toffoli, Marine Gilles, Rosaria Calabrese, Pierfrancesco Mitrotti, Luca Gallo, Alexandre Famechon, Sara Lucas Del Pozo, Roxana Mezabrovschi, Sofia Koletsi, Nadine Loefflad, Selen Yalkic, Naomi Limbachiya, Frederick Clasen, Suleyman Yildirim, Saeed Shoaie, Hervé Blottière, Christian Morabito, Aymeric David, Benoit Quinquis, Nicolas Pons, Emmanuelle Le Chatelier, Franco Valzania, Francesco Cavallieri, Valentina Fioravanti, Giulia Toschi, Fabio Blandini, Mathieu Almeida, Stanislav Dusko Ehrlich, Victoria Meslier & Anthony H. V. Schapira. Nature Medicine
DOI:10.1038/s41591-026-04318-5
Abstract
Microbiome signature of Parkinson’s disease in healthy and genetically at-risk individuals
Parkinson’s disease (PD) is a major cause of disability. GBA1 variants are the most common genetic risk factor for PD and increase the risk up to 30-fold. Why only approximately 20% of GBA1 variant carriers develop PD remains unknown.
Here, by combining clinical and fecal metagenomics data from 271 patients with PD, from 43 carriers of GBA1 variants not manifesting PD symptoms (GBA-NMC) and from 150 healthy controls, and using an innovative microbiome analysis, combining differential abundance of species and coherence of differential abundance variation between the groups as assessed by Cliff’s delta (δ), we show that the composition of a large component of the gut microbiome (approximately 25%) in GBA-NMC is intermediate between healthy controls and patients with PD.
This component is strongly correlated with disease progression in patients and prodromal symptoms suggestive of future development of PD in both GBA-NMC and healthy individuals.
We found microbiome alterations similar to those described here in three independent cohorts from the United States, Korea and Turkey, totaling 638 patients with PD and 319 healthy controls, and we conclude that gut microbiome alterations can identify both genetically and non-genetically at-risk individuals in the general population who may be progressing toward PD, thus serving as an early marker of disease development in the premanifest phase.
