Evolution of pro- and eukaryotic commensals within the human gut

The EPYC project will characterize the evolution of long-term human associated eukaryotes and prokaryotes, using colonization patterns in 3 human generations.The gut microbiome is important for human health, supporting nutrition, pathogen defence and immune homeostasis, with more than 200 species inhabiting each human gut. In recent years metagenomics led to notable breakthroughs in describing this microbial diversity, yet 50-90% of species are typically present at too low abundance to be genome or strain resolved. Thus, most gut microbiome studies focused to date on dominant bacteria and very little is known of the highly diverse, yet low abundance, pro- and eukaryotes (elusive microbes). Importantly, elusive microbes are an inherent part of ecosystem successions persisting at different ages of the host. I propose that niche adaptation and persistence are key indicators of a taxa’s importance to the gut ecosystem and host health. I will determine which microbes persist for years within a human, or even a family for several generations. This should be reflected in microbial genetic adaption, also indicating which genes are likely important to successfully colonize the human gut. I hypothesize that low abundance pro- and eukaryotes are adapted to persist for multiple generations in the human host, indicating their importance, despite being largely ignored so far.To investigate this knowledge gap in EPYC, I will(O1) Enable high-precision metagenomics of elusive microbes (O2) Estimate pro- and eukaryotic strain persistence across three human generations(O3) Describe the microbial genetics of gastrointestinal persistenceEPYC will develop the next-generation of high-resolution metagenomics of an extended taxonomic range, enabling me to research microbial evolution in the human gut.