Reduced Wheel Running via a High-Fat Diet Is Reversed by a Chow Diet with No Added Benefit from Fecal Microbial Transplants.

PURPOSE: Chronic overfeeding via a high-fat/high-sugar (HFHS) diet decreases wheel running and substantially alters the gut metabolome of C57BL/6J mice. In this study, we tested the hypothesis that fecal microbial transplants can modulate the effect of diet on wheel running. METHODS: Singly housed, 6-wk-old male C57BL/6J mice were fed either a grain-based diet (CHOW) or HFHS diet and provided a running wheel for 13 wk. Low-active, HFHS-exposed mice were then either switched to a CHOW diet and given an oral fecal microbial transplant from mice fed the CHOW diet, switched to a CHOW diet and given a sham transplant, or remained on the HFHS diet and given a fecal microbial transplant from mice fed the CHOW diet. Total wheel running, nutrient intake, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis were measured at various times throughout the study. RESULTS: We found that an HFHS diet decreases wheel running activity, increases body fat, and decreases microbial alpha diversity compared with a CHOW diet. Improvements in wheel running, body composition, and microbial alpha diversity were accomplished within 2 wk for mice switched from an HFHS diet to a CHOW diet with no clear evidence of an added benefit from fecal transplants. A fecal transplant from mice fed a CHOW diet without altering diet did not improve wheel running or body composition. Wheel running, body composition, fecal microbial composition, fecal metabolite composition, and liver steatosis percentage were primarily determined by diet. CONCLUSIONS: Our results suggest that diet is a primary mediator of wheel running with no clear effect from fecal microbial transplants.

A High Fat/High Sugar Diet Alters the Gastrointestinal Metabolome in a Sex Dependent Manner.

The gut metabolome offers insight for identifying the source of diet related pathology. As such, the purpose of this study was to characterize alterations of the gut metabolome in female and male C57BL/6J mice randomly assigned to a standard "chow" diet (CHOW) or a high fat/high sugar diet (HFHS; 45% fat and 20% fructose drinking solution) for nine weeks. Cecal metabolites were extracted and an untargeted analysis via LC-MS/MS was performed. Partial Least Sums Discriminate Analysis (PLS-DA) presented significant differences between the two diet groups in a sex-dependent manner. Mann-Whitney U-tests revealed 2443 and 1669 features to be significantly different between diet groups in the females and males, respectively. The majority of altered metabolites were depleted within the cecum of the HFHS fed mice. Metabolic pathways associated with galactose metabolism, leukotriene metabolism, and androgen and estrogen biosynthesis and metabolism were differentially altered with an HFHS diet between sexes. We concluded the immense metabolite depletion and elevation of adverse metabolites associated with the HFHS diet is suggestive of poor gut health. Further, the differential alterations between female and male mice suggests that sex plays an important role in determining the effect of diet on the metabolome and host health.