Dissecting microbiome-gut-brain circuits for microbial modulation of host cognition in response to diet and stress
Abstract
Mammals are comprised of trillions of microorganisms, together called the microbiome, that respond to environmental factors, such as diet and stress, and have the remarkable capacity to modulate host brain activity and behavior. Despite increasing evidence that the gut microbiome influences brain development and function, the molecular mechanisms that enable microbiota-gut-brain interactions remain unclear. Fundamental principles are lacking for how complex microbial communities develop and respond to external stimuli, and unified models are needed to map the dynamic microbial, enteric, metabolic, immune and neural signaling networks that comprise the microbiota-gut-brain axis. To address this need, we will investigate how the gut microbiome alters cognitive sensorimotor and spatial learning behavior in response to variations in dietary fat: carbohydrate intake and exposure to oxygen deprivation stress. Technical Approaches. We will conduct controlled gnotobiotic and microfluidic experiments to determine how the microbiome is altered as a function of fat: carbohydrate intake and physical hypoxic stress and to uncover how these microbiome changes causally impact host physiology. These experimental data will be used to develop a multilayered mathematical model of the microbiome-gut-brain axis that examines system architecture, performance, sensitivity and robustness. Altogether, the proposed project integrates advances in functional genomics, microfluidics, gnotobiotics, metabolic modeling, optogenetics, and control theory. Anticipated Outcome: Through iterative in vivo, in vitro and in silico experiments, with cross-referenced testing of predictions across experimental systems, we will extract fundamental biological insights for i) how nutrition and physical stress modify microbial community structure and function, ii) how microbial products biotransformed through the gastrointestinal tract modulate metabolic, immune and vagal signaling, and iii) how metabolic, immune and vagal activity determine cognitive performance. Impact on DoD Capabilities: The mathematical models we develop would enable predictions of microbiome, immune, metabolic, vagal and behavioral responses based on quantitative inputs of dietary fat vs. carbohydrate intake and physical stress (oxygen) levels. This could inform cognitive and physiological performance of individuals based on diet and stress.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 07, 2018
- Source ID
- W911NF1710402
Entities
People
- Elaine Hsiao
Organizations
- Army Contracting Command
- United States Army
- University of California, Los Angeles