Characterizing Microbes and How They Impact Human Health
Open AccessIn recent years, the microbiome has emerged as a concept in biomedical sciences. Broadly, the microbiome is a collection of microscopic organisms across taxonomic domains including viruses, bacteria, fungi, and archaea that live on and inside of a host. In human health, microbes often interface with their host in diverse roles including metabolism, immune system alliances, and transcriptional regulation. Microbes transferred from mothers via breast milk to infants can provide protective effects and bioactive components that influence infant health across time. Microbes transferred in different ways, such as through the process of fecal microbiota transplantation, can alter gut microbiome composition and regulate the production of bile acids which are important factors in metabolic diseases such as Type II Diabetes. Microbes of the pathogenic variety, such as SARS-CoV-2, the agent that causes COVID-19, can elicit harmful responses mediated by the immune system and which, in turn, alter the bacterial microbiome of host airways. Even the human genome harbors microbes in the form of endogenous retroviruses — nucleotide fossils that are the remnants of ancient retroviral infections that seem to play key roles in autoimmune disease and neurological health. Methods to characterize the microbiome holistically are lacking. In this dissertation, I aim to expand the set of methods available to characterize the microbiome. I present methods of sequence analysis to analyze SARS-CoV-2 genomic diversity and the association of genomic features with epidemiological data. I present novel results in the analysis of microbiome compositional data and potential role of fecal microbiota transplantation in the modulation of bile acid profiles. I probe the role of human endogenous retroviruses in systemic lupus erythematosus and in Alzheimer’s Disease, highlighting particular genomic loci that are transcriptionally dysregulated in disease states. I present evidence that human endogenous retrovirus’ proximity to genes in biological pathways may be related to disease pathogenesis. Finally, I develop a new classification system for human endogenous retroviruses and show how evolutionarily distinct clusters of human endogenous retroviruses play differing roles in immune activation and cytokine signaling.
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