Parkinson’s disease (PD) is usually diagnosed only after movement problems appear, when more than half of dopamine-producing neurons in the brain have already been lost. By that point, the biological processes driving degeneration have likely been underway for years. A new international study, published in Nature Medicine, suggests those early changes may be detectable not in the brain, but in the gut.
Researchers led by University College London (UCL), in collaboration with European partners, report that the composition and function of gut microbes can distinguish people with PD from healthy individuals, and potentially identify those at higher risk of developing the condition. The findings point to a shared microbial signature that appears to track with both disease presence and severity.
Tony Schapira, a neuroscientist and senior author of the study, has spent much of his career working on PD, investigating its genetic and biological causes as well as developing treatments aimed at slowing disease progression. The most commonly known genetic risk factor for PD is a mutation in the GBA1 (glucosylceramidase beta 1) gene, with 10-15 percent of people with PD carrying a GBA1 variant.
However, only around 20 percent of individuals carrying a GBA1 variant will go on to develop PD, meaning the majority remain unaffected. This has led scientists like Schapira to wonder what else determines disease penetrance in those individuals.
There has been growing interest in the gut microbiome in Parkinson’s disease over the past few years, and studies have identified differences in microbial composition. However, these have not been clearly linked to clinical features or disease progression.
—Tony Schapira, UCL
“That is why we began to consider whether the microbiome might be influential,” Schapira told DDN. “There has been growing interest in the gut microbiome in Parkinson’s disease over the past few years, and studies have identified differences in microbial composition. However, these have not been clearly linked to clinical features or disease progression.”
This significant knowledge gap ultimately led the team to develop a species-based microbiome score designed to capture PD-associated microbial changes — not only in patients, but in ostensibly healthy individuals who may already be biologically closer to disease than clinical assessments suggest.
A signal in the gut
The study analyzed stool samples from 271 people with PD, 43 individuals carrying a GBA1 variant but with no symptoms, and 150 healthy controls. Using shotgun metagenomics, the researchers mapped both the taxonomic and metabolic structure of the gut microbiome across groups. They also validated findings in independent cohorts from the US, Turkey, and Korea.
Across datasets, the researchers found a consistent pattern. More than a quarter of microbial species differed in abundance between people with PD and healthy controls. Some species were enriched in disease, while others were depleted, forming a reproducible Parkinson’s microbiome signature.
Interestingly, there was no significant difference in gut microbiome composition between people with PD who carried a GBA1 variant and those who did not. “In retrospect, that probably reflects the fact that as the disease develops and becomes established, the microbiome evolves in a way that overcomes any genetic influence,” said Schapira.
In contrast, disease-free GBA1 carriers showed a different pattern. Their gut microbiomes often appeared to sit in an intermediate state between healthy controls and patients with PD. Importantly, those carriers whose microbiomes more closely resembled the Parkinson’s-associated signature were also more likely to exhibit subtle non-motor symptoms associated with early disease, including autonomic dysfunction, urinary changes, and cognitive impairment.
We also assessed the healthy control group in great clinical detail, and a smaller proportion of individuals showed the microbiome signature. Importantly, those individuals also had very early, subtle features of Parkinson’s disease.
—Tony Schapira, UCL
The researchers also observed a similar pattern in the healthy control group. “We also assessed the healthy control group in great clinical detail, and a smaller proportion of individuals showed the microbiome signature,” Schapira said. “In those people, it was present in a less developed form, but I think it would be reasonable to say that this represents the beginning of the evolution of the Parkinson’s microbiome signature. Importantly, those individuals also had very early, subtle features of Parkinson’s disease.”
A measurable risk signature
To translate these findings into a more clinically usable format, the researchers developed a 16-species composite score, dubbed the Parkinson’s Disease Microbiome Score-16 (PDMS-16). The score quantifies how closely an individual’s gut microbiome resembles the Parkinson’s-associated pattern.
PDMS-16 distinguished patients from healthy controls and tracked with disease severity. Within the study cohort, those with the highest PDMS-16 scores were more likely to report depression and anxiety, had more autonomic symptoms, and showed dietary patterns associated with lower-quality nutrition.
“It could serve as a useful biomarker of risk,” Schapira said. “It is not difficult to do, and once established, it is not expensive. That makes it potentially scalable for population use.”
Cause, consequence, or both?
A central challenge in microbiome research is determining directionality. Do microbial changes contribute to disease onset, or do they arise as a consequence of early disease processes?
Schapira is cautious on this point. “We see changes in Parkinson’s disease, but we need to distinguish cause from effect,” he said. “It may be both.”
The study provides several clues. The microbiome signature was present in drug-naïve patients, suggesting it is not driven by medication. It also correlated with disease severity but not strongly with disease duration, implying it may evolve alongside pathology rather than simply reflecting chronic illness.
Diet also appeared to play a role. Dietary indicators such as the Dietary Quality Score and fruit and vegetable intake were lower in those with more pronounced microbiome alterations, pointing to a potential link between poorer diet quality and a more adverse disease profile.
“We found a very clear association with diet quality,” Schapira noted. “That suggests the microbiome is modifiable.”
Toward earlier detection
This work has exciting implications for both early diagnosis and potential treatment. If gut microbial signatures can reliably flag individuals at higher risk of PD years before the onset of motor symptoms, they could form part of a much earlier screening strategy — long before irreversible neuronal loss has occurred.
This would enable earlier intervention and improve stratification for clinical trials of emerging therapies. It also raises the possibility that the gut microbiome could act as a therapeutic itself. If microbial changes are contributing to inflammatory or metabolic pathways implicated in PD, then modifying the gut environment — through diet, fecal microbiota transplant, or other approaches — could become a future route for slowing or even altering disease progression.
However, researchers are cautious. At this stage, the findings are associative, and it remains unclear whether microbiome changes are a cause, consequence, or parallel feature of early disease processes. Longitudinal studies following high-risk individuals over time will be essential to determine whether these microbial signatures can truly predict who goes on to develop PD.
