Tailoring Gut Microbiota for Enhanced Resilience and Performance Under Sleep-Deprived Conditions

Abstract : Sleep deprivation has been associated with an increase in overall mortality and morbidity. Mechanistically, a loss of brain mass, due to neuronal death, has been observed after chronic sleep deprivation. Sleep deprivation also has enormous impacts on metabolic homeostasis, with increased prevalence of weight gain and obesity. Interestingly, perturbation of gut microbiota presents a pattern of metabolic abnormalities mirroring those induced by sleep deprivation. In this study, perturbation of gut microbiota and host functions following sleep deprivation will first be determined, using a humanized rat model, which is derived by transplanting native human gut microbiota into germ-free rats. This microbiota perturbation effect is based upon our hypothesis that sleep deprivation initially causes degradation in the functional and structural integrity of the gastrointestinal tract. Data generated will be used to develop a predictive metabolic network model of host-microbiota interaction. This model will be validated under various conditions of gut microbiota modulations using prebiotic, probiotic and synbiotic approaches. The validated model will be used to identify targets that can effectively tailor the gut microbiota and counter the adverse effects of sleep deprivation, resulting in enhanced host resilience and performance. This study is a four year project, the current report describes the accomplishments during the first year including establishment of the rodent germ-free facilities, selection of the human donors, and the creation of the pseudo germ-free animal model. This report also describes the work plan and future direction of the project.