Gut microbiome evolution via nature verses nurture: the affect of changing environments on the developing mammalian gut microbial ecosystem and immunity

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The human gastrointestinal tract is colonized with a diverse range of symbiotic bacteria and other microorganisms, collectively known as the gut microbiota. This population of microorganisms, and their genetic material is referred to as the gut microbiome. The gut microbiome has been linked to human metabolism, gut development and normal physiology, immune maturation and tolerance, and more recently with brain processes and behavior. The gut microbiome is a microbial ecosystem that operates much like a microbial organ that functions to promote health and prevent disease. Understanding how the gut microbiome affects disease susceptibility like inflammatory bowel disease is the basis of my health-related research funding through Crohn's and Colitis Canada and submitted to CIHR. The basis of my NSE-related work is understanding the basis of how the gut bacterial community structural assemblages form in the mammalian gut with a focus on the role of the environment. While there is evidence to support that the gut microbiota is vertically transmitted from the mother it is also believed that the environment is a source of microbes that are acquired in the gut through horizontal transmission. Yet, the role of the external environment in gut microbiome development is poorly understood. In this proposal, we set out to gain a fundamental understanding of how nature vs nurture influences horizontal and vertical transfer of microbes in the mammalian gut. Overall, my research serves to understand the complex relationship between the external environment, the intestinal microbiota and gut mucosal immunity. Largely, I hypothesize that intestinal colonization by the microbiota is a control point that shapes immune tolerance and consequently, immune maturation. Thus, over the next five years I will examine factors that affect the gut microbiome and its impact on immune development. My short term goals of this research program over the next 5 years will focus on the following objectives. Objective 1: To understand the effects of the environment on the development of the gut microbiome in the mammalian gut. Objective 2: To understand the how environment-primed gut microbiomes impact host immunity. Significance: The lack of understanding about the impact of host and environmental factors on microbial variation within the mammalian gut is an obstacle for translating knowledge of the microbiome for application. This research will shape our understanding about the role of various environmental and genetic factors on the gut microbiota composition, diversity and assembly, identify major research challenges for nature vs nurture gut microbiome studies and how this effects the microbe-host dynamic in the gut. This will help delineate the mechanism(s) behind how the microbiome affects intestinal immune maturation and immunotolerance important for understanding how the gut microbiota influences not only local but also systemic immune outcomes.