Edward Deehan | ALES Graduate Seminar

Date(s) - 11/05/2020
9:00 am - 10:00 am

A graduate exam seminar is a presentation of the student’s final research project for their degree.
This is an ALES PhD Final Exam Seminar by Edward Deehan. This seminar is open to the general public to attend.

**Please join the remote meeting 10-15 minutes early to prevent disruption at the start of the seminar.**

Thesis Topic: Targeted Application of Dietary Fibers for Selective Modulation of the Gut Microbiota and Improved Human Health

PhD with Drs. Jens Walter and Carla Prado.

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Conference ID: 559670596

Seminar Abstract:Observational and preclinical research provides convincing evidence for the health benefits of dietary fiber (DF); however, human interventions with purified DFs have produced inconsistent results. Between-study heterogeneity might stem from inter-study differences in the application of purified DFs. The first goal of this dissertation was to summarize the effects of DF supplementation on immunometabolic disease markers in humans, and consider the role of DF dose, DF physicochemical properties, length of intervention, and the placebo. A systematic review of 77 publications revealed that purified DFs reduced markers of insulin resistance and cholesterol concentrations in 36-49% of interventions, while <20% of interventions reduced dysglycemia and inflammation measures. A higher proportion of interventions showed an effect if they used higher DF doses for C-reactive protein (CRP) and total cholesterol (40-63%), viscous and mixed plant cell wall DFs for total cholesterol (>50%), and longer durations for CRP and glucose (50%). Although additional research is needed, a more targeted application of DF with specific physicochemical properties at higher doses and for longer durations shows promise in enhancing immunometabolic outcomes.

Clinical responses to purified DFs show a high degree of inter-individual variation, which further contributes to between-study heterogeneity. Variability might stem from individualised gut microbiota responses to DF, both in terms of composition and metabolite outputs relevant to health. Since microbiomes function as complex inter-connected communities, understanding what drives this individuality requires an ecological perspective. The second goal of this dissertation was to characterize the effects of high-dose arabinoxylan (AX) consumption on fecal microbiota composition and short-chain fatty acids (SCFAs), as compared to 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 specific taxa including Bifidobacterium longum and Prevotella copri (q<0.15, Wilcoxon test), and increased propionate (p=0.012, Friedman’s test). Individualized metabolic effects of AX on the gut microbiota were linked to compositional shifts and its baseline composition (q<0.05, MLR models), providing evidence that such responses might be predictable.

While DF fermentation by gut microbiota generates beneficial metabolites, gases are also produced. Elevated colonic gas production causes flatulence, bloating, and other adverse symptoms. Therefore, the degree to which efficacious amounts of DF are tolerated by humans and what determines inter-individual differences in tolerance remains insufficiently understood. The third goal of this dissertation was to evaluate gastrointestinal tolerance and adaptation towards high-dose AX supplementation and assess links to pre-treatment fecal microbiome and diet. This study showed that AX caused symptoms during the first weeks of supplementation relative to MCC, but subjects ‘adapted’ with symptoms reverting to baseline levels towards the end of treatment (p<0.05, Mann-Whitney tests). Adaption responses were individualized and correlated with baseline Bifidobacterium longum abundance (rs=0.74, p=0.002), AX-induced shifts in acetate (rs=0.54, p=0.039), and habitual consumption of meat/meat alternative proportional to whole grains (rs=-0.54; p=0.042) and cholesterol (rs=-0.58; p=0.027). These study findings provide a basis for the development of strategies to improve the tolerance of efficacious DF doses.

Strong associations between the gut microbiome and chronic disease provide rational for the development of strategies that target the gut microbiota for improved health. However, it is unknown whether precise and predictable manipulations of the gut microbiota and its metabolic activity are achievable through discrete DF structures. The fourth goal of this dissertation was to determine if discrete differences in DF structure could be used to direct changes in fecal microbiota composition and its SCFA output. 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 microbiome, 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 a basis for the targeted application of tolerable purified DFs to selectively modulate gut microbiota composition and functions relevant to health and to improve immunometabolic effects in humans.