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Targeted Application of Dietary Fibers for Selective Modulation of the Gut Microbiota and Improved Human Health
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- Author / Creator
- Deehan, Edward C
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Obesity and associated comorbidities have reached epidemic proportions worldwide. Observational studies provide consistent evidence that plant-based diets rich in dietary fibers (DFs) reduce chronic disease risk. Mechanistic studies have established processes by which DFs improve health, with one emerging mechanism being the modulation of gut microbiota composition and its functions. However, results from human interventions with purified DFs remain inconsistent with extensive between-study heterogeneity. Therefore, questions remain as to whether DFs can exert reliable health effects when a reductionist approach is used with purified DFs, what the efficacious doses are, and if such doses are tolerable. The overall goal of this dissertation was to explore the potential of purified DFs to improve human health through more targeted approaches. This was achieved by the following objectives.
The first objective of this dissertation was to summarize the effects of purified DFs on immunometabolic disease markers in humans and consider the role of DF dose, physicochemical properties, intervention duration, and the placebo. Systematic review of 77 publications revealed that purified DFs reduced markers of insulin resistance and cholesterol in 36-49% of interventions, while 50%), and longer durations for CRP and glucose (50%). Although additional research is needed, a more targeted application of purified DF with specific physicochemical properties at higher doses and for longer durations shows promise for improved clinical efficacy.
As both the dose and physicochemical properties of DF were relevant to health, the second objective was to characterize the effects of high doses of soluble, fermentable arabinoxylan (AX) on fecal microbiota composition and short-chain fatty acids (SCFA), as compared to insoluble, non-fermentable microcrystalline cellulose (MCC), and integrate findings using an ecological framework. Using a randomized controlled design, we showed that AX exerted global shifts to bacterial community composition (AX-vs-MCC: baseline p=0.17, week 6 p=0.019, PERMANOVA), promoted Bifidobacterium longum and Prevotella copri (q<0.15, Wilcoxon test), and increased propionate (p=0.012, Friedman’s test); bacterial taxa and a SCFA previously linked to immunometabolic benefits. SCFA responses to AX were individualized and linked to compositional shifts and its baseline composition (q<0.05, MLR models), providing evidence that such responses might be predictable.
The third objective of this dissertation was to evaluate the gastrointestinal tolerance of fermentable AX at efficacious amounts relative to non-fermentable MCC and systematically investigate links to fecal microbiota and diet. This study showed that AX increased symptoms during the first three weeks of supplementation relative to MCC (p<0.05, Mann-Whitney tests), but subjects ‘adapted’ with symptoms reverting to baseline levels towards the end of treatment. Adaption responses were individualized and correlated with the relative abundance of B. longum at baseline (rs=0.74, p=0.002), within the bacterial community that actively utilized AX ex vivo (rs=0.69, p=0.006), AX-induced shifts in acetate (rs=0.54, p=0.039), and greater habitual consumption of meat/meat alternative relative to whole grains (rs=-0.54; p=0.042) and cholesterol (rs=-0.58; p=0.027). These findings provide a basis for the development of strategies for improved tolerance of efficacious DF doses.
The final objective was to determine if specific doses of discrete DF structure could be used to direct changes in fecal microbiota composition and its output of beneficial SCFAs. Using a dose-response trial with three type-IV resistant starches we found that crystalline and phosphate-cross-linked starches induce divergent effects on the gut microbiota, promoting either Eubacterium rectale (q=0.007, two-way repeated measures ANOVA) and butyrate (p=0.05) or Parabacteroides distasonis (q=0.005) and propionate (p=0.04), respectively. These effects were dose-dependent plateauing at 35 g/day and remarkably consistent with respective E. rectale and P. distasonis enrichments detected in all subjects. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiota and its functions relevant to health.
Together findings in this dissertation provide evidence that purified DFs could exert more reliable effects in humans; however, targeted approaches are needed that apply higher doses of specific DF structures and consider individualized responses. Findings also provide a basis for the development of more precise nutritional strategies based on purified DFs that selectively modulate the gut microbiota and improve immunometabolic outcomes.
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- Graduation date
- Fall 2020
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.