Effects of soluble corn fiber on cognition in older adults: Integrating clinical, in vitro, and bioinformatics approaches to explore gut-brain interactions

The gut microbiome is a critical mediator in the optimization of human health through diet. Although robust evidence links dietary fiber consumption to improvements in gastrointestinal and metabolic outcomes, its potential to enhance cognitive function via gut–brain axis pathways remain underexplored. To address this gap, we integrated data from a human clinical trial, in vitro experiments, and multi-omics analyses to elucidate the interconnections among dietary fiber intake, gut microbial dynamics, and cognitive health. For our investigation (Chapter 2), we conducted a randomized crossover clinical trial to evaluate the effects of daily consumption of soluble corn fiber (SCF) for 4 weeks on cognitive function in older adults (45-75 years) and to assess the mediating and moderating influence of the microbiota using 16S rRNA gene-sequenced fecal data on these cognitive outcomes. Next, we sought to further understand if gut bacterium differentially enriched by the intervention could metabolize the SCF in isolation or if the enrichment observed in the clinical trial stems from cross-feeding interactions within the colon. Finally, we examined the microbiome profiles on a subset of participants, categorized as responders and non-responders, using shotgun metagenomic sequencing on their fecal samples to capture snapshots of their microbial functional capacity before and after the intervention, thereby reinforcing the concept of nutrition as a personalized intervention. We discovered that daily consumption of SCF numerically increased fecal acetate, improved attentional inhibition measured by their reaction time, and induced an enrichment of Parabacteroides that exerted a moderating effect. Furthermore, we observed that Parabacteroides distasonis was capable of metabolizing SCF when provided as its sole substrate for growth following an adaptation period, as evidenced by its diauxic growth pattern. In addition, the predicted imputed metagenome of the full cohort suggested increased functional capacity resulting from SCF consumption, and the quantified metagenome demonstrated distinct profiles between responders and non-responders. Together, this integrative approach not only deepens our understanding of the multifaceted roles of SCF but also underscores the importance of incorporating dietary fibers into the diet of older adults as a strategy for harnessing their potential cognitive benefits within personalized nutritional interventions.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Alvarado, David Anthony

Contributors dc:contributor

• Holscher, Hannah D
• Swanson, Kelly S
• Khan, Naiman A
• Miller, Michael J

• Gut-Brain
• Parabacteroides: Soluble Corn Fiber
• Attentional Inhibition
• Microbiome

Statement dc:rights

• Copyright 2025 David Anthony Alvarado

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129751

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129751