Investigating the host-microbe dialogue in aging
University College Cork
This thesis aimed to investigate the role of the gut microbiota and their associated functionality in the context of aging and life stage related diseases. The focus was maintained on key inter-kingdom signalling molecules, host produced but bacterially modified Bile acids (BAs) and on dietary microbially derived Fatty acids (FAs) as key elements to indicate gut microbial potential impactful roles. In the context of Chapter 3, this thesis examined the levels of BAs and FAs, to identify convergence on specific microbially produced, or modified, metabolites in the two neurological disease states representing (1) early life (murine model of Autism Spectrum Disorder (ASD)) and (2) later life (human Parkinson’s Disease (PD)). It further established the potential to redress the balance through microbial intervention, as a cause or consequence in the case of ASD. BAs converged during the healthy aging process, in Chapter 4, to determine the nature of these specific interactions, based on nuclear receptor conservation. The Caenorhabditis elegans nematode model of aging was employed to determine and genetically decipher potential individual BA influences. Chapter 5 built on recognising that gut microbes and the pathobiont Escherichia coli HM605 induced inflammation. This chapter also focused on the mechanisms by which Escherichia coli HM605 could influence the aging process.
Gut microbiota , Aging , Bile acid , Fatty acid , Autism spectrum disorder , Parkinson’s disease , Caenorhabditis elegans , Escherichia coli , Crohn's disease
Killian, C. 2022. Investigating the host-microbe dialogue in aging. PhD Thesis, University College Cork.