(OR14-02-24) Designed Dietary Fiber Prebiotics for Gut-Brain Axis Health

Objectives: The gut-brain axis is a crucial bidirectional link in which gastrointestinal health influences brain function. This concept suggests that managing gut microbes can boost both gut and overall health, including brain wellness. This research aimed to: (1) assess if prebiotic fibers can increase short chain fatty acids (SCFAs) production in individuals with Parkinson's disease (PD), and (2) create a prebiotic blend to aid key gut bacteria for health. Additionally, the health impacts of this prebiotic blend were tested in a clinical trial on PD patients.

Methods: We utilized in vitro fecal fermentations using inocula from healthy individuals and those with PD to strategically design a dietary fiber prebiotic mixture to support a broad range of health-promoting gut bacteria (accessed through 16S rDNA sequencing) and beneficial metabolites (SCFAs). Furthermore, a clinical trial was conducted using the designed prebiotic in individuals with PD (20g/day for 10 days), and health markers were evaluated, including bacterial composition (shotgun sequencing of fecal samples), gut inflammation (fecal calprotectin), barrier integrity (plasma zonulin), and a marker of neurodegeneration (NfL).

Results: The in vitro data showed that PD microbiota is responsive to dietary fiber fermentations, increasing SCFA production similarly to healthy controls. Moreover, 4 fiber types were selected to compose the designed prebiotic (resistant starch, rice bran, resistant maltodextrin, inulin), each shown to promote complementary beneficial taxa and elicit specific SCFA responses. The clinical trial demonstrated that the designed prebiotic was tolerable and, in only 10 days, was effective in promoting beneficial gut microbes, reducing Proteobacteria levels (a phylum known to be related to gut inflammation; P = 0.003, q = 0.016), and improving gut barrier function (evidenced by reduced zonulin levels, P = 0.001). Additionally, the prebiotic supplementation reduced intestinal inflammation and lowered NfL levels (P = 0.044 and 0.003, respectively).

Conclusions: These findings underscore the potential of designed prebiotics in modulating the gut microbiota to improve gut and whole-body health in individuals with neurological conditions.

Funding Sources: Consolidated Anti-Aging Foundation, NIH grants, Christine and John Bakalar, and philanthropic funding.