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Exercise and the Gut Microbiome in Mice Selectively Bred for High Voluntary Wheel-Running Behavior

Abstract

The gut microbiome is essential for normal host function. My dissertation examined the gut microbiome in juvenile and adult mice, including effects of exercise, diet, and antibiotics. As a model, I studied mice from 4 replicate High Runner (HR) lines that are bred for voluntary wheel-running behavior and their 4 non-selected Control (C) lines. Chapter 1 examined the juvenile gut microbiome in females from generation 81. Fecal samples were taken 24 hours after weaning. HR mice had higher relative abundance of the family Clostridiaceae compared to C mice. Based on beta diversity metrics, the 4 replicate HR lines differed from one another as did the 4 C lines. As part of a larger study, Chapter 2 examined effects of exercise training on adult body composition, organ masses, and food and water consumption. Four weeks of wheel access increased heart mass and decreased body fat for both HR and C mice. Chapter 3 tested for long-lasting effects of early-life Western diet and/or exercise. Males from generation 76 were given 3 weeks of Western or standard diet and/or wheel access or no wheels starting at 3 weeks of age, then placed on a standard diet without wheels for 8 weeks, followed by fecal sampling. Western diet, exercise, and linetype (HR versus C lines) had an interactive effect on alpha diversity; in addition, Western diet decreased alpha diversity in all groups. Early-life Western diet also decreased the relative abundance of Muribaculum intestinale. Based on beta diversity metrics, HR and C mice had differing adult gut microbiome communities. Chapter 4 investigated effects of antibiotic treatment on wheel-running behavior in adult females from generation 89. Mice were given wheels for 2 weeks, then antibiotics in drinking water for 10 days, then returned to tap water for 12 days. Antibiotics reduced aerobic colony forming units from fecal samples to non-detectible levels and reduced wheel-running behavior in the HR, but not C lines. Antibiotics did not affect food consumption, nor did they appear to cause sickness behavior. These results suggest the HR microbiome is an important component of their high wheel-running phenotype.

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