Parkinson’s disease (PD) is the most prevalent neurodegenerative disease. While genetic variants in the GBA1 gene represent the most common genetic risk factor for PD, only about 20% of individuals carrying it will develop the disease. However, the largest proportion of individuals who develop PD have no known genetic factors and the gut microbiome could contribute to disease pathogenesis1.
New findings in Nature Medicine belonging to the Aligning Science Across Parkinson’s (ASAP) research initiative identify specific gut microbiome signatures that could identify risk of Parkinson’s disease years before symptoms appear2.
The authors recruited in Great Britain and Italy, a cohort of 150 healthy individuals, 43 carriers of GBA1 variants who were free of disease and 271 patients with PD. All study participants were examined clinically for symptoms of PD and collected fecal samples for gut microbiome composition analysis. An innovative microbiome analysis allowed to reveal which species were enriched or depleted in each individual and explore the proportion of the microbiome altered.
Microbiome alterations varied notably among individuals of each study group. The gut microbiome was altered in carriers of GBA1 mutations compared to healthy people. Higher levels of gut microbiome alteration strongly correlated with a greater risk of developing overt disease, with 10% of early-stage individuals already showing the highest levels of alteration.
Alterations levels in the gut microbiome were more pronounced in patients with PD and were consistently seen in British, Italian, but also in American, Turkish and Korean participants from 3 other independent cohorts. These alterations were independent of medication and correlated positively with the severity of disease but negatively with diet quality. Species that showed the greatest increase in PD included Streptococcus mutans, Bifidobacterium longum, B. dentium and Lactobacillus paragasseri, whereas species that showed the greatest depletion in PD included Roseburia intestinalis, R. inulinivorans and an unclassified Faecalibacterium. These species represented about 25% of the gut microbiome.
Among healthy people, approximately 20% of individuals with the most altered microbiome were closer to diseased individuals and consumed diets of lower quality, suggesting a possible relation between food quality (ie, fruit and vegetable consumption) and milder disease profile. These results suggest that the gut microbiome evolves gradually from healthy people, across those at genetic risk, to patients who are symptomatic. Interestingly, gut microbiome alterations in patients with PD were independent of medication and correlated positively with the severity of the disease but negatively with diet quality.
To sum up, gut microbiome alterations emerge as a non-genetic risk factor that could help identify individuals at highest risk of developing overt disease years before disease onset. A healthy diet is associated with these alterations and might mitigate disease risk. These findings also suggest that modulation of Parkinson’s could be possible through targeting microbiome alterations associated with the severity of the disease.
“Microbiome analysis could identify individuals at highest risk of Parkinson’s disease years before disease onset and the risk might be mitigated by diet”.
References:
- de Castro Fonseca M, Zanetti L, Fanourakis S, et al. The gut microbiome, systemic inflammation, and autoimmunity in Parkinson’s disease. Lancet Neurol. 2026; 25(1):103-114. doi: 10.1016/S1474-4422(25)00382-5.
- Menozzi E, Ren Y, Geiger M, et al. Microbiome signature of Parkinson’s disease in healthy and genetically at-risk individuals. Nat Med. 2026; 32(6):2096-2106. doi: 10.1038/s41591-026-04318-5.
