PROJECT SUMMARY As biological scientists and even as members of an educated society, we all have some familiarity with the fundamental concept that some aspects of our health are influenced by the set of genes we obtained from our parents. We are also increasingly aware that our body surfaces, from our skin to our intestine, harbor microbial strains that also influence our health. Given recent discoveries that many of our microbes are stably colonized for decades and are acquired in early life, it is perhaps unsurprising that some proportion of the microbes inside you right now were likely acquired from your parents and/or siblings when you were a child and maintained in your intestine to this day, potentially influencing your health for these past many years. In addition, we rarely find commensal gut microbial strains shared between two unrelated individuals outside of extreme circumstances of microbial transfer such as fecal microbiota transplantation. Given the extreme uniqueness of microbial strains at the genome level and the rarity of each strain variant, fecal microbiota transplantation and familial-shared microbes represent the most efficient route to accurately track and infer basic principles of microbial transmission and sharing. We feel this grant renewal will continue to address important gaps in our basic science knowledge of gut microbiota transmission. Just as tracking of classical acute pathogenic microbes plays a key role in disease prevention and treatment, uncovering the basic principles of microbial sharing and transmission for non-acute pathogen microbes could enable new tools to quantify disease risk, to understand the importance of the familial microbial strain sharing in disease risk, to manipulate the gut microbiota to improve health, and ultimately perhaps to enable the prevention of disease through controlled monitoring or therapeutic manipulation of the microbiota to minimize disease risk.