Impact of the Intestinal Microbiota on the Host Epigenome and Obesity Phenotype

University Of Nebraska Lincoln, Lincoln NE

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Abstract

The human gastrointestinal tract is populated with as many as 100 trillion bacteria that provide their host with dietary metabolites and protection against pathogens. Increasing evidence indicates appropriate intestinal 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 impacting long-term gene regulation with consequences for health. The intestinal microbiota has also been implicated in obesity, a chronic inflammatory condition now associated with early life events affecting assembly of the gut microbiota, including cesarean sections, antibiotics, and formula feeding. These observations suggest that disruption of the early gut microbiota may lead to metabolic deficiencies later in life through epigenetic mechanisms; however, the specific microbiota-regulated targets that influence the obese phenotype are currently unknown. Dr. Ramer-Tait will test the hypothesis that the lack of symbiotic microbiota during early development precipitates regulation of proinflammatory T cell phenotype genes via epigenetic mechanisms, with long-term consequences for metabolic health. She will combine gnotobiotic mouse models with high-throughput sequencing technologies to study the interactions 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 gnotobiotic 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 relationships, we can strategically design novel dietary interventions to control obesity by modulating the intestinal microbiota.