Evaluating substrate utilisation to target newly identified health-promoting gut bacteria

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Lordan, Cathy
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University College Cork
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Promoting the growth and/or activity of potentially beneficial human gut microorganisms through the provision of specific substrates has been the subject of many studies over recent decades. Such substrates can include prebiotics, which promote growth in a targeted manner, but prebiotics can also be combined with other less target-specific nutrients to further enhance the growth of these targets. This field has continued to advance in recent years and has also expanded in response to the identification of new target species, such as Akkermansia muciniphila, Eubacterium rectale, Faecalibacterium prausnitzii, Roseburia inulinivorans, and Ruminococcus bromii, many of which produce metabolites that can contribute to host health. These developments have been in part due to improvements in culture-based techniques, advances in DNA sequencing-based approaches and improved computational pipelines. The combined use of these tools has enormous potential with respect to elucidating substrates that can be applied to specifically target microbes of interest and is the focus of this thesis. Chapter 1 reviews the literature relating to prebiotics, and potential prebiotics, with a focus on more recently identified health-promoting gut bacteria. Building on this, in Chapter 2 we applied both in silico and in vitro techniques to predict and assess substrate utilisation for seven strains across five species of interest. The bioinformatics-based component of Chapter 2 is expanded in Chapter 3 through the analysis of publicly available microbial genomes of the same species of interest and, through the creation of metabolic models, predicting the substrates that these microorganisms could consume. Finally, in Chapter 4 we employ an ex vivo model to evaluate, through shotgun metagenomic sequencing, the impact different substrates, including simple sugars, oligosaccharides, and whey protein concentrate had on the taxonomic composition and functional potential of a colonic microbiome. Thus, facilitating the design and testing of a functional prototype beverage comprised of some substrates assessed here. Overall, this thesis explores different substrates that could be applied to target the growth and/or activity of recently identified health modulating microbes within the human gut. Combining in silico, in vitro, and ex vivo approaches have the potential to identify and assess a variety of substrates that may be applied to bring about microbiome-mediated enhancements of host health.
Microbiology , Computational biology
Lordan, C. 2021. Evaluating substrate utilisation to target newly identified health-promoting gut bacteria. PhD Thesis, University College Cork.