PR000659 (Project)

Description:As diabetes becomes a growing heath concern, afflicting nearly 25.8 million people in the United States and nearly 220 million people worldwide, there has been an increased awareness of environmental factors like diet that are contributing to the disease. In diabetic patients, a major causal factor contributing to progression of the disease is hyperglycemia, although the underlying mechanisms by which hyperglycemia impairs homeostatic processes are not well understood. While we know that early intensive glycemic control reduces the risk of cardiovascular complications in humans and rodent models, there is a large gap in studies of the etiology of hyperglycemia-induced alterations in the disease. To combat high sugar diets that could contribute to diabetes and subsequent hyperglycemia, non-caloric artificial sweeteners have become one of the most utilized food additives worldwide due to their consideration as a low caloric substitute. However, supporting scientific data as to the safety of these non-caloric artificial sweeteners is limited and controversial. The negative implications of consuming a high sugar diet on overall health have long been linked to diabetes, obesity, and resulting systemic health problems; however, it was not until recently that the negative impact of consuming artificial sweeteners in the place of sugar had been increasingly recognized. Recent evidence also suggests that a diet rich in artificial sweeteners can induce glucose intolerance through the alteration of the gut microbiome. We hypothesize that a specific subset of plasma metabolites are generated as a result from a diet rich in commonly used artificial sweeteners and their subsequent processing by the gut microbiome, which could ultimately lead to impaired glycemic control and negative physiological health outcomes. To test this hypothesis this study will 1) administer a diet high in glucose, fructose, and 4 common artificial sweeteners separately to rats followed by a plasma metabolic analysis (AIM 1) and 2) treat the gut microbiota with antibiotics in these animals to observe how alterations of the microbiome influence the plasma metabolic profile in animals receiving the altered diets (AIM 2). The resulting data will give us insights into the influence of high sugar and artificial sweetener diets on homeostatic metabolic processes and dive into the symbiotic relationship of the gut microbiome with this process. This data will provide crucial insights into the dietary use of artificial sweeteners in the replacement of sugars and how it alters metabolic pathways that could potentially lead to altered states of obesity, diabetes, and cardiovascular disease.