Increasing evidence indicates that changes in respiratory homeostasis and disordered breathing, such as obstructive sleep apnea, intermittent hypoxia or exercise can modulate or are associated with changes in the gut microbiome. Additionally, alterations to gut microbiome have been hypothesized to play a role in autoimmune diseases, social behavioral deficits, and metabolic diseases such as diabetes and cardiovascular disease. We therefore aimed to determine if a model of gut dysbiosis, the absence of a gut microbiome, would result in alterations to respiratory homeostasis.In order to determine if the lack of a gut microbiome would alter respiratory homeostasis, we assayed 8‐week‐old C57bl6J germ‐free (GF, n=24) and specific‐pathogen‐free (SPF, n=24) mice under normoxic (21%O2, 79%N2) conditions and challenging them with hypercapnic (5%CO2, 21%O2, 74%N2) and hypoxic (10%O2, 90%N2) environments. Whole‐body flow through plethysmography was used to monitor respiratory function and metabolic demand in conscious and unrestrained animals. The experimental protocol consisted of 5 days of habituation to human handling and chamber acclimation prior to respiratory assessment. GF mice habituation was performed inside the germ‐free isolator prior to exiting them for testing. To determine if gut colonization of GF mice may alter respiratory function, 12 GF mice assayed by plethysmography and then orally inoculated with fecal samples from SPF donor mice, while 12 SPF control mice were assayed for respiratory function and then inoculated with sterile saline. All animals were then placed back into the SPF facility for 3 weeks to allow for gut colonization.Mice were analyzed for respiratory rate (Vf), tidal volume (VT), minute ventilation (VE), oxygen consumption (VO2), and minute ventilation normalized by oxygen consumption (VE/VO2). For GF vs SPF experiments 2‐way ANOVA was performed with Bonferroni multiple comparison correction and a p<0.05 was used to indicate statistical significance. No difference between GF and SPF mice for any parameter was found. For GF gut recolonization experiments, no significant difference was found within group comparing pre‐ and post‐recolonization and between groups. Pre‐ and post‐recolonization data was compared using a paired t‐test while the comparison between groups was done by a 2‐way ANOVA with Bonferroni multiple comparison correction. A p<0.05 was used to indicate statistical significance.Overall these results suggest that the gut microbiome is dispensable for normal respiratory function and respiratory chemoreflexes in adult mice and that the lack of a gut microbiome, a model of gut dysbiosis, does not result in significant changes in respiratory homeostasis.Support or Funding InformationMcNair Medical InstituteThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.