Factors which modulate the ecology of the intestinal microbiome and the effect on colonic immunity

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The intestinal microbiome is a complex and diverse environment of microbes that contributes 100X more genetic material to the host's intestinal environment with which it intimately interacts. The microbiota normally lives in harmony with the intestine, plays a significant role in the development of intestinal immune responses in neonates, and is thought to maintain the adult intestine in a controlled state of physiological inflammation. Considering the microbiota resides at the interphase of the gut mucosa, alterations made to the microbiota's ecology likely have a significant impact on the host's immune responses with wide-ranging consequences since components of the intestinal microbiome play a crucial role in the early development of both local and systemic immunity. In fact, dysbiosis, or altered microbial populations, has been observed in various disease phenotypes like IBD, obesity and diabetes. Understanding factors that can influence the ecology of the microbiome, such as nutrition, physical activity, and the dynamics of intestinal microbiome changes during the process of aging, may offer insight into the role each population of bacteria plays during intestinal homeostasis. In this context, my research goals are to understand the impact of environmental determinants on the intestinal microbiome. I hypothesize that our current dietary pattern and decline in physical activity adversely modulates the intestinal microbiome and changes intestinal immune responses. Using diet- and exercise-based interventions in control and murine models of intestinal inflammation, and in vitro techniques, we will examine i) the effect of lifestyle factors, such as diet and exercise, on changing the ecology of the intestinal microbiota; ii) the impact of these ecological changes on intestinal inflammation; and iii) compare the effects from neonate to geriatric periods and determine if these ecological and immunological changes are transient or long-term.