Project Summary: Why are some species particularly susceptible to cancer while others develop very little cancer? We have discovered wide variation in cancer prevalence across species. However, we can explain only a small fraction of that variation. We hypothesize that the microbiomes of species may explain part of their cancer prevalence. Specifically, we hypothesize that microbiome diversity prevents pathogenic microbes from dominating and so should be associated with lower cancer prevalence across species. We also hypothesize that microbial species that have been associated with cancer in humans will be associated with higher neoplasia and malignancy prevalence across animals. Likewise, microbial species associated with lower cancer prevalence in humans will be associated with lower neoplasia and malignancy prevalence across animals. We will also test for cancer prevalence associations with microbes that have not been previously connected to cancer. We will download publicly available microbiome 16S rRNA data for the 164 species in our comparative oncology database for which we have at least 50 necropsy reports. If 16S rRNA data is lacking for any of those species, we will collaborate with the Phoenix and other zoos to acquire stool samples that we will sequence to profile the gastrointestinal microbiome. Because diet and microbiome are factors that are much more easily modified than many other variables that may explain cancer prevalence, such as basal metabolic rate, the results of our analyses are potentially translatable to cancer prevention in humans.