UC San Diego

The essential role of microbiota in macroscopic organisms has led to a coining of the term “metaorganism”, which encompasses a multicellular host organism and the various microbial communities found within it. Humans depend on the many microbial communities found within and around them to survive. However, reproducible and mechanistic studies of these communities have remained frustratingly elusive in many instances due to the challenges of replicating in vivo community behavior in an in vitro laboratory setting. This dissertation seeks to address this problem and demonstrate the benefits for human health that can be obtained through microbiome studies. The first chapters present the development of reproducible synthetic soil and skin microbial communities, to be used for in vitro study of community dynamics and targeted interventions on microbiome composition. Studies with these tools show that final community diversity and composition can be modulated by minor adjustments in starting inoculum, with certain organisms driving the final state of the community. This knowledge of community dynamics can be used, for example, to support design of soil microbial communities to increase agricultural plant growth in a sustainable fashion. Additionally, growth of the skin community with cosmetics compounds probes the effect on these compounds on skin microbiota, which has implications for development of skin pathologies. Finally, a later chapter presents the use of a sialidase isolated from the gut microbiome to reduce cardiovascular disease development in a humanized mouse model by removing the sialic acid N-glycolylneuraminic acid from the endothelium. This study takes a novel enzyme and applies it in a new way, seeking to use microbiome studies to benefit the host organism on multiple levels. Together this body of work bridges the in vitro and in vivo aspects of microbiome research to implement novel strategies for partnering with the microbiome to support and advance human health.