Exploration of a novel organometallic complex to restore gut health in rats consuming an obesogenic diet

Exploration of a novel organometallic complex to restore gut health in rats consuming an obesogenic diet Exploration of a novel organometallic complex to restore gut health in rats consuming an obesogenic diet Principle Aim: Identify the mechanism by which administration of an organometallic complex prevents intestinal dysbiosis. Despite the prevalence of poor dietary habits during adolescence and young adulthood, the relationship between the gut microbiome and symptoms associated with metabolic syndrome (MetS) induced by poor nutrition is not well understood. The gut microbiome and its broad genetic make-up consists of trillions of microbes living on the surface of our skin, in our mouths, noses, and digestive systems1-3. In a healthy adult, the intestine harbors a diverse community of bacteria where the predominate genus of microbiota present includes Bacteriodetes and Firmicutes2. Under normal healthy conditions, bacteria in the gut outnumber host cells and have a significant impact on the host physiology1. Diet-induced changes of the gut microbiome (unbalanced ratio of Bacteriodetes and Firmicutes) have been associated with the development of cardiovascular disease, hypertension, obesity and hyperglycemia; symptoms associated with MetS and type 2 diabetes4. Additionally, the gut microbiota plays a vital role in regulating the intestinal epithelial barrier. Therefore, alterations in the microbiota can increase the abundance of gram-positive bacteria that release lipopolysaccharides which impair tight junction proteins and increase intestinal permeability. Previous research has shown that a high fat diet (HFD) can increase intestinal permeability and subsequently translocate pathogenic bacteria to vital organs, such as the liver, skeletal muscle and adipose tissue. Ultimately, bacterial translocation can result in an inflammatory response and metabolic insulin resistance5. Previous studies have used complex polysaccharides to promote health following poor dietary consumption6,7. The proposed study will be the first to examine the transformation of the gut microbiota through the administration of an organometallic complex which may encourage the growth of beneficial bacteria and reduce intestinal permeability, systemic inflammation and lead to improved measures of metabolic health in 6-week-old rats consuming HFD. A prior study in our lab has shown that a novel organometallic complex (OMC) prevents endotoxemia in rats consuming a high fat diet for 10 weeks. Therefore, we propose to study the mechanism that can explain how this OMC intervention prevents gut dysbiosis by characterizing the gut microbiome of these animals.