Date of Award

Spring 1-1-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Integrative Physiology

First Advisor

Monika Fleshner

Second Advisor

Benjamin N. Greenwood

Third Advisor

Christopher A. Lowry

Abstract

The mammalian intestine harbors a complex microbial ecosystem that affects many aspects of host physiology. Exposure to specific microbes early in development can significantly impact host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may be more sensitive to environmentally evoked change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity status can increase the abundance of some beneficial microbial organisms. We therefore investigated whether exercise initiated in the juvenile period (P24) would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (P70) in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and less diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered the relative abundance of several phyla, and notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. Analyses of bacteria at the genus level using supervised learning approaches along with ANOVA also revealed potential functionally significant changes, and indicated that juvenile onset exercise dramatically changed the abundance and presence of genera important for metabolism and emotional behavior. Among these genera, juvenile onset exercise increased Lactobacillus spp. just three days following exercise onset. A follow up investigation utilizing bacterial culture methods and Lactobacillus spp. selective media confirmed these results, and also showed that at the species level, juvenile onset exercise can induce early increases in L. rhamnosus, a species shown to modulate a diverse array of host functions including carbohydrate metabolism and anxiety. Given the potential of these phyla and genus level changes to contribute to a lean phenotype, we chose to examine body composition in juvenile versus adult runners. Interestingly, exercise increased lean mass measured using chemical carcass analyses and in vivo MRI, in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbial composition as well as body composition depends on the developmental stage during which exercise is initiated. Furthermore, early life exercise produced robust, adaptive changes in bacteria associated with body composition, host metabolism and behavior, suggesting that a microbiome altered by exercise during early life could contribute to life-long improvements in mental and physical health.

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