Integrative analyses of the associations between diet, the human gastrointestinal microbiota, and metabolic health

Baldeon, Alexis David

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https://hdl.handle.net/2142/129740 Copy

Description

Title

Integrative analyses of the associations between diet, the human gastrointestinal microbiota, and metabolic health

Author(s)

Baldeon, Alexis David

Issue Date

2025-04-29

Director of Research (if dissertation) or Advisor (if thesis)

Holscher, Hannah D

Doctoral Committee Chair(s)

Burd, Nicholas A

Committee Member(s)

• Allen, Jacob M
• Gaulke, Christopher A

Department of Study

Nutritional Sciences

Discipline

Nutritional Sciences

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Human nutrition
• intestinal microbiome
• metabolic health

Abstract

Diet is an important modifiable lifestyle factor that regulates the risk of developing non-communicable diseases and modulates the human intestinal microbiome. Clinical and pre-clinical research has increasingly associated unique microbiota profiles with these diet-related diseases, suggesting a mediating role of these microbial communities between diet and health. Therefore, the dietary modulation of the human intestinal microbiome poses a safe, cost-effective mechanism to prevent, manage, and perhaps treat these diseases. To develop the microbiome-centered nutritional strategies and guidelines necessary to improve human health, clinical evidence is needed to outline the interrelationship between diet, the intestinal microbiome, and markers of metabolic health. To this end, this dissertation completed four studies in adult cohorts investigating the connections between dietary patterns and a whole-food intervention with the intestinal microbiome and further integrating these findings with metabolic health data. The first project was a cross-sectional analysis examining the differences in the fecal microbiota composition of adults based on diet quality. A final cohort of 432 adults from the American Gut Project was divided into tertiles based on their Healthy Eating Index-2015 scores, an assessment of compliance to key recommendations of the Dietary Guidelines for Americans. The differences in taxonomic abundances and diversity were compared between high and low scorers. Adults with greater compliance with the Dietary Guidelines demonstrated higher diversity in their fecal microbiota and a greater abundance of bacteria capable of metabolizing complex carbohydrates. These results provide evidence of how the Dietary Guidelines support the gut microbiota. The second study aimed to determine the unique contributions of fecal taxa and metabolites in predicting metabolic health markers across various dietary patterns. This cross-sectional analysis measured the adherence of 118 adults to the dietary approaches to stop hypertension (DASH), Mediterranean diet, Mediterranean-DASH intervention for neurocognitive delay (MIND), and the Healthy Eating Index-2020 (HEI-2020). Microbiota features that associated independently with these dietary patterns and with metabolic health markers were selected as predictor variables for hierarchical linear regression models. Integrating these select fecal taxa and metabolites alongside dietary indices in these regression models significantly improved metabolic health marker prediction. These results suggest that the intestinal microbiota potentially underpins physiological responses to diet and highlights potential microbial biomarkers of metabolic health. The third study was a secondary data analysis of a controlled-feeding, randomized control trial with a cross-over design evaluating the effect of almond consumption on the fecal microbiome and inflammatory and metabolic markers in a cohort of 15 adults. Participants consumed 42g (treatment) or 0g (control) of almonds daily for three weeks with washout periods in between. Results revealed a decrease in circulating total cholesterol, LDL cholesterol and triglycerides in the almond group compared to control. There were no observed effects of almond consumption on the structure or function of the intestinal microbiome. These results reveal that eating 42g of almonds daily for three weeks in a controlled-feeding setting has a beneficial impact on the lipid profile of adults but no significant effect on the fecal microbiome. The objective of the last study was to determine the effect of daily almond consumption on the human intestinal microbiome and metabolic health in a cohort of 28 free-living adults. This study was a randomized, controlled, parallel-arm clinical trial where healthy adults consumed 56g or 0g of whole almonds for 12 weeks. Results revealed a marginal increase of Roseburia spp in the microbiota of adults who consumed almonds, accompanied by a significant increase in the relative concentration of butyrate. However, there was no effect of almond consumption on the taxonomic or functional diversity of the intestinal microbiome. A treatment-specific effect was observed on the postprandial responses of glucose, insulin, non-esterified fatty acids, inflammatory markers, and circulating bile acids. Further, exploratory analyses revealed inverse correlations between the postprandial response of circulating bile acids and glucose in response to almond consumption. Together, these results suggest that almond consumption impacts the structure and metabolism of the intestinal microbiome, and these changes are associated with glycemic control. In conclusion, our data supports the notion that long-term dietary habits and short-term whole-food interventions are effective strategies to modulate the intestinal microbiome. Further, these diet-induced changes in the structure and function of these microbial communities associated with markers of metabolic health across cohorts, adding to the existing evidence that points to a causal role of the microbiome in supporting host health. Future research integrating expanded multi-omics datasets with larger cohorts is warranted to continue to untangle the complex interrelationship between diet, the intestinal microbiome, and human health.

Graduation Semester

2025-05

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/129740

Copyright and License Information

Copyright 2025 Alexis David Baldeon

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