Todd, O. A.; Vu, L. D.; Jan van Hengel, I. A.; Statkus, B.; Van den Abbeele, P.

Parkinsons disease (PD) is associated with altered gut-brain signaling, including microbial dysbiosis, intestinal inflammation, and reduced short-chain fatty acid (SCFA) production. Because dietary fibers are selectively fermented by intestinal microbes to generate SCFAs, fiber formulations tailored to the altered intestinal environment in PD offer a strategy to modulate microbial dysfunction. Here, we used the ex vivo Systemic Intestinal Fermentation Research (SIFR) technology platform, which enables assessment of gut microbiome modulation and host-relevant readouts with demonstrated translational relevance, to assess how fiber substrates influence microbial composition and metabolism of fecal microbiota from individuals with PD (n = 6). Fecal samples were incubated for 24 h with single-fiber, multi-fiber, and food-based formulations. Fermentation outputs, including pH, gas, and SCFAs, were quantified, and select formulations were further characterized by profiling microbial community structure and metabolite output. Relative to a parallel untreated control and osmotic laxative comparator, multi-fiber formulations increased SCFA production (~2-fold, p = 0.001). These effects were accompanied by increased microbial biomass (~1.5-fold, p = 0.0007), enrichment of fiber-responsive taxa, and coordinated shifts in metabolites associated with gut-brain signaling. Collectively, these findings show that fiber blend complexity and formulation context shape microbial metabolic engagement, supporting formulation-dependent modulation of gut-derived metabolites linked to gut-brain signaling in PD.