The human gastrointesfinal tract is populated with as many as 100 trillion bacteria that provide their host with dietary metabolites and protecfion against pathogens. Increasing evidence indicates appropriate intesfinal microbiota colonization during early stages of life is important for preventing immune-mediated diseases later in life. A key question is: How does the early intestinal microbiota provide these long-term benefits? Evidence is emerging that the human gut microbiota participates in the creation of epigenetic marks, thereby impacfing long-term gene regulafion with consequences for health. The intesfinal microbiota has also been implicated in obesity, a chronic inflammatory condifion now associated with eariy life events affecfing assembly of the gut microbiota, including cesarean secfions, anfibiofics, and formula feeding. These observafions suggest that disrupfion of the early gut microbiota may lead to metabolic deficiencies later in life through epigenetic mechanisms; however, the specific microbiotaregulated targets that influence the obese phenotype are currently unknown. Dr. Ramer-Tait will test the hypothesis that the lack of symbiotic microbiota during eariy development precipitates regulation of proinflammatory T cell phenotype genes via epigenetic mechanisms, with long-term consequences for metabolic health. She will combine gnotobiofic mouse models with high-throughput sequencing technologies to study the interacfions among the microbiota, the immune system, and the epigenome in the context of obesity. During her project. Dr. Ramer-Tait will employ her extensive training in immunology, microbiology, and gnotobiofic mouse models of inflammatory diseases. Her COBRE mentors include a well-respected molecular microbial ecologist with expertise in high throughput sequence analyses and a bioinformatician with vast expertise in analysis of large data sets derived from genome sequencing projects. This project will advance the thematic focus of the associated proposed Nebraska Center for the Prevention of Obesity Disease through Dietary Molecules by providing critical information about how the gut microbiota regulates the host immune system and precipitates metabolic diseases. By understanding these host-microbial relafionships, we can strategically design novel dietary interventions to control obesity by modulafing the intesfinal microbiota.

Appreciation is growing for the role of non-dietary, environmental factors in obesity, including eariy-life events that impact intesfinal microbes and regulate the host epigenome. However, specific microbiotaregulated targets that influence the obese phenotype are currently unknown. This project will elucidate the interacfions among the microbiota, immune system, and epigenome in the context of obesity to facilitate future development of dietary strategies that modulate gut bacteria to prevent disease.