Restoration and Precision Modulation of the Gut Microbiome with Dietary Fibre Interventions to Improve Human Health
Creators: Armet, Anissa M.
Publisher: name: University of Alberta Library
Year: 2024

<p>Industrialization depletes the gut microbiome and increases risk of chronic diseases. One contributing factor is reduced dietary fibre intake, representing an opportunity to improve health through fibre-based microbiome-targeted strategies. Increased fibre consumption can be achieved through whole-food approaches, which have well-established health benefits but can be difficult to implement. Fibre supplementation is a more feasible strategy, but nutritional research has questioned whether isolated and synthetic fibres maintain the health effects of fibres intrinsic to foods. Furthermore, the mechanistic role of the gut microbiome in the health effects of fibre and its contributions to the inter-individual variation in clinical responses are insufficiently understood. The objectives of this thesis were to investigate if dietary fibre interventions, based either on whole-foods or supplements, can redress the negative impacts of industrialization on the gut microbiome and improve risk markers of chronic diseases, and determine if clinical responses can be predicted by the microbiome using machine learning. To achieve this, two randomized controlled trials were conducted.</p>

<p>The first trial investigated the effects of a microbiome restoration strategy, comprising a high-fibre (~44grams/day) non-industrialized-type diet (Restore diet) and a probiotic species rarely found in industrialized microbiomes (Limosilactobacillus reuteri), on the gut microbiome and risk markers of chronic diseases. Healthy adults (n=30) with BMI 20-30kg/m2 consumed the Restore diet (every meal provided) or their usual diet in a crossover fashion for three weeks each. Participants were further divided into three groups and consumed a single dose of either L. reuteri or placebo during each diet period. While L. reuteri did not affect the microbiome or host, the Restore diet had diverse effects on gut microbiome ecology and function and induced significant benefits to risk markers with low inter-individual variation, reducing glucose (mean change of -6.3%; p&lt;0.001, linear mixed models), low-density lipoprotein cholesterol (-16.8%; p=0.003), C-reactive protein (-14.0%; p=0.014), and fecal calprotectin (-21.0%; p=0.011). Clinical responses were predicted by microbiome features redressed by the diet, such as reductions in mucus-targeted CAZymes and pro-inflammatory microbes (e.g., Bilophila). </p>

<p>We next investigated if clinical effects of physicochemically-distinct fibres could be predicted by baseline microbiome signatures. In a six-week parallel-arm trial, healthy adults with excess body weight (BMI 25-35kg/m2) added 25grams/day (females) or 35grams/day (males) of one of three fibres to their usual diet: acacia gum (AG; soluble, fermentable; n=75), resistant starch type IV (RS4; insoluble, fermentable; n=75), or microcrystalline cellulose (MCC; insoluble, non-fermentable control; n=45). The fermentable fibres had highly specific effects on the microbiome: AG increased Bifidobacterium longum (p&lt;0.001, Wilcoxon test), Faecalibacterium spp. (p&lt;0.01), acetate (p=0.009) and propionate (p=0.008), while RS4 increased B. adolescentis (p&lt;0.001), Parabacteroides distasonis (p=0.001), and butyrate (p=0.027). Interestingly, both AG and MCC reduced gut inflammation (median change of -33.8% and -34.4% in calprotectin; p=0.002 and p=0.017, respectively, linear mixed models) and all three fibres improved gut barrier function (-8.2% to -11.5% in lipopolysaccharide binding protein; p=0.012 to p=0.001). Although there were no significant effects on risk markers of disease, several clinical responses could be accurately predicted by baseline microbiome features using machine learning.  </p>

<p>The major findings of this thesis were that, although a non-industrialized-type diet and isolated, fermentable fibre supplements restored certain microbiome features negatively impacted by industrialization, they differed vastly in their physiological effects on the host. The Restore diet induced substantial clinical benefits with low inter-individual variation, several of which were linked to microbiome features redressed by the diet. These findings not only suggest a mechanistic role of the microbiome in the effects of the diet but also that the industrialized microbiome, although depleted, can still mediate certain benefits of a non-industrialized-type diet. In contrast to the Restore diet, the fibre supplements did not induce significant benefits to risk markers. However, several clinical responses could be accurately predicted by baseline microbiome features, thus establishing a basis for precision nutrition approaches for fibre supplements. In addition, both fermentable and non-fermentable fibre supplements improved markers of gut inflammation and barrier function, suggesting fermentation-independent clinical effects relevant for inflammatory conditions. Collectively, this research provides foundational evidence to optimize applications of fibre-based nutritional strategies, wherein high-fibre diets can be generally recommended for chronic disease prevention while fibre supplementation show promise for targeted clinical applications in specific patient populations that would further benefit from personalization.</p>