Anissa Armet | ALES Graduate Seminar

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 Anissa Armet. This seminar is open to the general public to attend, either in person or online:

https://ualberta-ca.zoom.us/j/4451587935?omn=96017117296

Thesis Topic: Restoration and precision modulation of the gut microbiome with dietary fibre interventions to improve human health

PhD with Drs. Carla Prado and Jens Walter.

Seminar Abstract:

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 nutritional strategies. However, the role of the gut microbiome in the health effects of fibre and its contributions to inter-individual variation in clinical responses are insufficiently understood. The objectives of this thesis were to investigate whether dietary fibre interventions, based either on whole-foods or supplements, can redress the negative impacts of industrialization on the 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.

The first trial tested a microbiome restoration strategy comprised of a diet recapitulating key characteristics of non-industrialized dietary patterns (‘Restore diet’) and a bacterium rarely found in industrialized microbiomes (Limosilactobacillus reuteri) in a controlled feeding trial in healthy adults (n=30). While L. reuteri did not affect the microbiome or host, the Restore diet had diverse effects on gut microbiome composition and increased production of short-chain fatty acids (SCFAs). Additionally, the diet significantly benefited risk markers with low inter-individual variation. It reduced plasma glucose by -6.3±11.1% (p<0.001), low-density lipoprotein cholesterol by -16.8±15.8% (p=0.003), and C-reactive protein by -14.0±58.3% (p=0.014). Clinical responses were predicted by microbiome features redressed by the diet, such as decreases in mucus-targeted carbohydrate-active enzymes (CAZymes) and pro-inflammatory microbes.

The second trial investigated if clinical responses to physicochemically-distinct fibres could be predicted by baseline microbiome signatures. In a six-week parallel-arm trial, healthy adults with excess body weight 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 induced highly selective effects on gut microbiome composition and production of SCFAs. Both AG and MCC reduced fecal calprotectin (-33.8±51.4% and -34.4±62.9%; p=0.002 and p=0.017, respectively), and all three fibres improved plasma lipopolysaccharide binding protein (-8.2±17.7% to -11.5±33.1%; p=0.012 to p=0.001), markers of gut inflammation and barrier function, respectively. There were no significant effects on risk markers of chronic diseases, with high inter-individual variation in responses. However, clinical responses could be accurately predicted by baseline microbiome features, such as microbial pathways and CAZymes.

In summary, both the Restore diet and isolated fermentable fibre supplements restored certain microbiome features negatively impacted by industrialization. The Restore diet induced substantial clinical benefits, with low inter-individual variation, that were linked to microbiome features redressed by the diet, suggesting that the industrialized microbiome can still mediate certain benefits of a non-industrialized-type diet. In contrast, the fibre supplements did not induce significant benefits to risk markers; however, clinical responses could be predicted by baseline microbiome features, thus establishing a basis for precision nutrition approaches involving fibre supplements. Fermentable and non-fermentable fibre supplements improved gut inflammation and barrier function, suggesting fermentation-independent effects relevant for inflammatory conditions. Collectively, this research provides evidence to optimize applications of fibre-based nutritional strategies, wherein high-fibre diets can be generally recommended for chronic disease prevention while fibre supplementation shows promise for targeted clinical applications in specific patient populations that would further benefit from personalization.