Introduction The gut microbiota is intricately connected with host health and is known to influence gene expression across multiple organ systems. Both animal and human longitudinal studies have demonstrated that exercise has independent effects on the composition and functionality of the gut microbiota. Previous studies performed by our group have also shown that transplant of an “exercised” microbiota into germ‐free mice confers enhanced protection against colitis compared to transplant of a “sedentary” microbiota. In this study, we assessed how an “exercised” microbiota transplant impacts global gene expression in gut, brain, and muscle tissue compared to a “sedentary” microbiota transplant. Methods Donor mice received access to a running wheel (n=10) or remained without access (n=9) for six weeks prior to euthanasia. Donor cecal contents were pooled by activity group and transplanted into two separate groups of recipient germ‐free mice (n=16 for each group). After five weeks of gut microbial colonization, recipient mice were sacrificed, and tissues were collected. Total RNA was isolated from the distal colon, soleus muscle, and hippocampus. Four representative mice were chosen from each group for whole transcriptome analysis (RNAseq) of these tissues. Anticipated Results We hypothesize that mice that received an “exercised” microbiome will have different global gene expression profiles than those that received a “sedentary” microbiome. We predict that genes related to immune function, cellular metabolism, and gut barrier function may be particularly affected by transplant of the “exercised” microbiome. Support or Funding Information This work supported by a grant from the Mayo Clinic‐University of Illinois Alliance for Technology‐based Healthcare. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .