Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale

Shafieinouri, Mohammad, Hong, Samantha, Lee, Paul Suhwan, Grant, Spencer M, Khani, Marzieh, Dadu, Anant, Schumacher Schuh, Artur F, Makarious, Mary B, Sandon, Rodrigo, Simmonds, Emily, Iwaki, Hirotaka, Hill, Gracelyn, Blauwendraat, Cornelis, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Qi, Yue A, Noyce, Alastair J, Reyes-Palomares, Armando, Leonard, Hampton L, Tansey, Malu, Faghri, Faraz, Singleton, Andrew B, Nalls, Mike A, Levine, Kristin S and Bandres-Ciga, Sara 2025. Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale. Science Advances 11 (35) , eadu2937. 10.1126/sciadv.adu2937

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: Title: cc by-nc, Type: cc by-nc
Publisher:	American Association for the Advancement of Science
Date of First Compliant Deposit:	9 September 2025
Date of Acceptance:	31 July 2025
Last Modified:	09 Sep 2025 09:16
URI:	https://orca.cardiff.ac.uk/id/eprint/180998

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