Fiber Formulation-Dependent Modulation of Gut Microbial Metabolism in Parkinsons Disease

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(R)) 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/718214v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@f84f37org.highwire.dtl.DTLVardef@18ad9borg.highwire.dtl.DTLVardef@2dd28eorg.highwire.dtl.DTLVardef@5a8da7_HPS_FORMAT_FIGEXP M_FIG C_FIG