(LB03-05-25) Food-as-Medicine: Modulating Impaired Gut-Brain Pathways Toward Health With a Targeted Prebiotic

Objectives: The gut microbiome plays a key role in health, yet current interventions often fail to demonstrate targeted microbiome shifts that alter disease progression. We showed previously that targeted prebiotics can be designed to elicit robust and consistent responses in people. In our Parkinson’s disease (PD) trial, a targeted prebiotic mixture reshaped the gut microbiome, enhanced gut barrier function, and reduced gut and brain inflammation. With growing recognition of food-as-medicine in disease management, this study aimed to investigate whether this prebiotic intervention affected biochemical pathways relevant to PD progression.

Methods: A comprehensive proteomic analysis was conducted on plasma extracellular vesicles (EVs) from 20 patients with PD before and after 14 days of daily targeted prebiotic (20g/day), alongside 10 age-, sex-, and race-matched healthy controls. EVs are lipid-bound carriers of proteins, lipids, RNA, and microbial components, mediate intercellular communication and serve as biomarkers of systemic biological changes, aiding in monitoring disease progression and therapeutic responses.

Results: Host-derived EV proteins in individuals with PD differed significantly from healthy controls, with several up- and downregulated pathways. Importantly, the prebiotic led to shifts in 73 host-derived EV proteins (fold change ≥ 1.5), reversing PD protein signatures back towards the healthy controls. Pathway enrichment analysis showed modulation of key biological processes, including inflammation regulation, neural repair, dopaminergic function, and adaptive immunity. Microbiome-associated EV patterns mirrored fecal gut microbiota changes post-prebiotic intake, with an increase in SCFA-producing taxa and a reduction in potentially harmful taxa (Enterobacteriaceae, Desulfovibrionaceae), better resembling that of the healthy controls.

Conclusions: These findings support a food-as-medicine approach, demonstrating that targeted prebiotics move both microbial composition and host proteomic responses in PD towards a healthy signature. By shifting key biological pathways toward a healthier profile, prebiotics emerge as a non-pharmacological, potential disease-modifying strategy for PD.

Funding Sources: 1U01DK140923-01, R01 AG056653, Mrs. & Mr. Glass, Mrs. & Mr. Burks Philanthropy.