Reacción a "A study shows that changes in the gut microbiome can identify people at risk of developing Parkinson's disease"

This study aligns with and strongly supports the “body-first” model of Parkinson’s disease, which suggests that the disease may begin with alterations in the enteric and autonomic nervous systems before spreading to the brain. Evidence of changes in the microbiome had already been observed in patients with diagnosed Parkinson’s disease and in animal models. The major contribution demonstrated here is that a significant component of the microbiome (approximately 25%) already shows alterations in individuals with genetic risk but no symptoms (GBA-NMC), representing an intermediate state between healthy controls and patients with Parkinson’s disease.

From a methodological standpoint, this study combines comprehensive clinical data and fecal metagenomics from a primary cohort of 464 individuals and employs a novel analysis based on the consistency of bacterial abundance variation across different groups (assessed using Cliff’s delta). This allows for the detection of subtle yet consistent changes across a large proportion of the microbiome, rather than focusing solely on extreme variations in a few species. Thus, the researchers have taken a step further by creating a tool based on 16 bacterial species (PDMS-16), capable of identifying individuals in the general healthy population who exhibit a clinical profile closer to that of Parkinson’s patients. Equally important, the main findings of this study were not limited to the original cohort but were validated in three independent and geographically diverse cohorts (the United States, Korea, and Turkey), lending great robustness to the results obtained.

However, as the authors themselves note, the study design was cross-sectional (a snapshot at a given point in time) and included a small number of asymptomatic individuals at genetic risk (43 GBA-NMC individuals), so it cannot be confirmed which at-risk individuals will actually go on to develop the disease. Longitudinal studies over time are needed to confirm conversion to clinical Parkinson’s disease.

Although alterations in the microbiome or digestive disorders have previously been associated with neurodegenerative diseases such as Parkinson’s, several highly relevant conclusions can be drawn from this study that shift the perspective on the disease. Alterations in the gut microbiome evolve progressively with the development of the disease and are not merely a response to pharmacological treatment or to the late-stage symptoms of Parkinson’s. Furthermore, changes in certain bacterial species are strongly correlated with prodromal symptoms (those that precede motor symptoms by years), such as autonomic dysfunction, chronic constipation, REM sleep disorders, or depression. This is observed both in individuals with genetic risk and in the “healthy” population with a high vulnerability to developing the disease. The main conclusion is that the gut microbiome has real potential to serve as a non-invasive early marker. Assessing the composition of the microbiome could help identify, within the general population (with or without known genetic risk), those individuals who are in the preclinical phase and progressing toward Parkinson’s, opening a crucial window of opportunity for future preventive neuroprotective therapies.