Persistent and unique microbial communities impart the majority of genetic and metabolic diversity in humans, and their composition and activity are important indicators of health and disease. The Whiteson lab uses culture-independent metagenomics, metabolomics, and ecological statistics along with hypothesis driven, reductionist microbiology to answer questions about how bacteria and viruses affect human health. We and others find that the most important source of variance in both microbiome and metabolome data is the individual the sample was taken from, making longitudinal samples where a person’s own sample can act as the baseline an important approach. Several recent research projects using metabolomics and sequencing will be presented from healthy humans and Cystic Fibrosis patients, with the hope of brainstorming analytical approaches to relate longitudinal microbiome and metabolomics data.