Science advancesAug 27, 2025

Mapping connections between the gut and brain linked to neurodegeneration in a large population

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

Several disorders were associated with increased risk of Alzheimer's disease (AD) and Parkinson's disease (PD) before diagnosis.

Endocrine, nutritional, metabolic, and digestive disorders may have causal or temporal links to AD/PD risk.
The strength and timing of associations between these disorders and AD/PD risk varied across different conditions.
Lower genetic predisposition for AD/PD is observed in individuals with co-occurring disorders, as indicated by polygenic risk scores.
The protein profile of individuals with AD/PD is influenced by gut-brain axis disorders.
Multimodal prediction models could enhance disease classification compared to single-modality approaches.

Simplified

Alzheimer's disease (AD) and Parkinson's disease (PD) are influenced by genetic and environmental factors. We conducted a biobank-scale study to (i) identify endocrine, nutritional, metabolic, and digestive disorders with potential causal or temporal associations with AD/PD risk before diagnosis; (ii) assess plasma biomarkers' specificity for AD/PD in the context of co-occurring gut related traits and disorders; and (iii) integrate multimodal datasets to enhance AD/PD prediction. Our findings show that several disorders were associated with increased AD/PD risk before diagnosis, with variation in the strength and timing of associations across conditions. Polygenic risk scores reveal lower genetic predisposition for AD/PD in individuals with co-occurring disorders. Moreover, the proteomic profile of AD/PD cases was influenced by comorbid gut-brain axis disorders. Last, our multimodal prediction models outperform single-modality paradigms in disease classification. This endeavor illuminates the interplay between factors involved in the gut-brain axis and the development of AD/PD, opening avenues for therapeutic targeting and early diagnosis.