Date of Award

5-2025

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

First Committee Advisor

Suzanne Ishaq

Second Committee Member

Yanyan Li

Third Committee Member

Katherine Weatherford Darling

Additional Committee Members

Robert Beiko

Erin Grey

Abstract

Diet plays a critical role in shaping the gut microbiome, which in turn influences immune function, inflammation, and metabolic health. This dissertation investigates the complex interplay between dietary glucosinolates (GSLs), gut microbiota composition, and inflammation through a multi-faceted approach incorporating meta-analysis, preclinical murine models, and human dietary interventions. The research aims to elucidate how diet-induced shifts in the gut microbiome impact microbial metabolism of GSLs and their bioactive derivatives, with potential implications for mitigating inflammation-associated conditions such as inflammatory bowel disease (IBD). The introduction outlines microbiome development, microbial dysregulation in disease states, and the significance of host-diet-microbiome interactions and the role of GSLs in human health. A preclinical study utilizing an interleukin-10-knockout (IL-10-KO) mouse model of IBD assessed the effects of early-life exposure to broccoli sprouts. Results demonstrate that dietary intervention with GSL-rich foods enhances microbial diversity and protects against enterocolitis, suggesting that microbiome modulation during early development may have long-term health benefits. A human dietary intervention examined the effects of daily steamed broccoli sprout consumption on gut microbiota composition in healthy adults and individuals with self-reported bowel conditions. The study reveals diet-induced shifts in microbial diversity, with interindividual variability in microbiome responses, reinforcing the need for personalized dietary strategies to optimize gut health. A meta-analysis of publicly available gut microbiome datasets evaluated the impact of dietary patterns and Westernization on microbial diversity and functional capacity for GSL metabolism. The findings indicate that omnivorous diets exhibit greater abundance of specific GSL-converting species, and industrialized populations exhibit greater microbial diversity and abundance of specific GSL-metabolizing species, with notable gender-specific differences. Collectively, these studies highlight the potential of dietary interventions to modulate gut microbiota composition and function, emphasizing the role of microbiome-targeted nutrition in health promotion. Future research should focus on longitudinal and mechanistic studies to further delineate the pathways through which dietary components influence microbiome adaptation and inflammatory processes. This dissertation underscores the importance of integrating microbiome science into dietary recommendations and precision nutrition approaches to optimize human health.

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