Examining the Stress-Gut Microbiome Interface: A Systems Biology Approach

Grant Winners

Deans

Abstract

Unique, often diverse symbiotic microbial communities are harbored on and within most eukaryotic host organisms, including humans as “microbiomes”. The human gut microbiome represents one of the best studied microbial communities in nature. Intriguingly, recent research on the gut microbiome is calling attention to the considerable role that gut microbiome plays in influencing human behavior, metabolism, and disease states.  Indeed, in recognition of the crucial role gut microbiota play as distinct mediators of health and mental well-being, the general scaffolding of the brain-gut axis has recently been expanded to the brain-gut-microbiota axis (BGMA). One particularly exciting, yet understudied, function of the BGMA is that alterations to the microbiome can increase stress susceptibility through increasing psychological vulnerability. In particular, the impaired mood and cognitive control that occurs with altered gut microbiota sets the stage for a microbiota cascade. Here, stress alters the gut microbiome, which in turn alters brain function in a way that increases vulnerability to further stress. While this notion is interesting, it remains largely unexplored likely owing to the complex, multidisciplinary approach required to provide evidence for such a hypothesis. The current proposal will directly address this uncertainty by combining an interdisciplinary team of researchers to offer a novel approach to elucidate the bidirectional molecular and microbial mechanisms that drive chronic stress.

Towards accomplishing our long-term goal, and within the scope of this grant opportunity, we propose to test three specific aims: 1) Determine the relationship between chronic stress and gut microbiome diversity, 2) Determine the relationship between gut microbiota and psychological health and neurobehavioral task performance, and 3) Develop a mathematically driven model of the BGMA. Once the Aims of the proposed study are met, our primary deliverable will be a mathematical model of the bidirectional brain-gut-microbiome axis. In addition, findings from this study will offer a data-driven foundation for targeted countermeasures against dysregulation of the BGMA such as targeted probiotic-based therapies and directed autogenic therapy aimed at autonomic and stress (HPA) axis regulation.