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Supplemental Table 1. Gene expression in gastroc muscles of germ-free mice when compared to sedentary SPF control values.

Gene SED SPF CON Fold Change (2^-∆∆CT)

SED GF Fold Change (2^-

∆∆CT)

VWR GF Fold Change (2^-

∆∆CT)

Group p value

PGC1α 1.12±0.18 3.52±0.50* 3.51±0.79* 0.002

MCT1 1.02±0.06 0.62±0.04* 0.64±0.05* <0.001

LC3 1.03±0.08 1.41±0.23 1.87±0.22* 0.02

SDH 1.02±0.08 1.13±0.05 1.19±0.07 0.263

GLUT4 1.01±0.05 0.51±0.08* 0.44±0.07* <0.001

MCT4 1.04±0.09 1.03±0.12 0.81±0.17 0.410

PPARγ 2.18±1.25 62.65±10.18* 51.05±6.12* <0.001

Values are means ± standard error. *represents a significant (p<0.05) difference from respective sedentary SPF group. Note: these samples were obtained immediately after an acute exhaustive bout of exercise due to mitigate the potential for microbial

contamination making it difficult to interpret VWR training effect. N = 9, 10, and 8 for SPF SED, SED GF, and VWR GF, respectively.

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Supplemental Figure 1. Food (a) and water (b) disappearance in SPF mice.

Supplemental Figure 1. Food (a) and water (b) disappearance in SPF mice. Food and water disappearance was measured ~weekly during the course of the experiment in SPF mice. For food disappearance (a), *signifies that CON was significantly lower than both VWR and VWR/ABX groups. For water disappearance (b), *signifies that CON and VWR were significantly lower than ABX and ABX/VWR, while **signifies that CON was significantly lower than all other groups.

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Supplemental Figure 2. Effects of wheel running and broad spectrum antibiotic treatment on body weight change over time.

Supplemental Figure 2. Effects of wheel running and broad-spectrum antibiotic treatment on body weight over time in males (a) and females (b). There were significant time main effects for both sexes indicating that both gained weight during the experiment.

In males (2a), there was a significant time x VWR interaction (F18,270 = 10.7; p = 0.000) indicating that VWR mice had lower body weights over time. In females (2b), there were significant time x VWR (F18,270 = 2.25; p = 0.003) and time x ABX (F18,270 = 2.95; p = 0.000) interactions indicating that VWR mice gained weight in the latter stages of the experiment and ABX treatment also lead to weight gain late in the experiment. Data are mean + sem for n = 4-5 per group.

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

21 22 23 24 25 26 27 28 29 30 31

CON

VWR ABX

VWR/ABX Males

Time Points

Body Weight (g)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

17 18 19 20 21 22 23 24 25

CON VWR ABX

VWR/ABX Females

Time Points

B o d y W e ig h t (g )

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Supplemental Figure 3. Body weight changes over time for male (a) and female (b) SPF mice

CON

VW

R ABX

VWR ABX GF

GF VWR

0 1 2 3 4 5

6 a

a,b a

b

c c

a) Males

Group

B o d y W e ig h t C h a n g e ( g )

CON

VW

R ABX

VWR ABX GF

GF VWR

0 1 2 3 4 5 6

* *

b) Females

Group

B o d y W e ig h t C h a n g e ( g )

Supplemental Figure 3. Body weight changes over time for male (a) and female (b) SPF mice. For males (a), there were

significant (<0.001) time and time x exercise effects (driven largely by lower body weights in VWR), and for females (b), there were significant (<0.001) time, time x exercise, and time x ABX effects.

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Supplemental Figure 4. Total area under the curve (AUC) for 30, 60, and 90 minute timepoints during intraperitoneal glucose tolerance test

Supplemental Figure 4. Total area under the curve (AUC) for 30, 60, and 90 minute timepoints during intraperitoneal glucose tolerance test. When the 0 minute (baseline) timepoint is omitted, ABX did not affect total AUC, but Germ free status significantly increased it (p<0.001). This was unaffected by VWR in all groups. Data are mean + sem for n = 9, 10, 9, 9, 10, and 9 for CON, VWR, ABX, ABX VWR, GF, and GF VWR respectively.

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Supplemental Figure 5. Effects of ABX or germ-free status on diurnal wheel running behavior

Supplemental Figure 5. Effects of ABX or germ-free status on diurnal wheel running behavior. There were significant (p < 0.05) time and time x group effects, but no main effect of group. asignifies a difference between VWR and GF VWR, crepresents difference between GF VWR and both other groups. Data are mean + sem for n = 9, 9, 10, and 8 for VWR, VWR/ABX, and GF VWR,

respectively.

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