The significance of a healthy gut microbiome, and the detriment of alterations in microbiota composition, on host physiology is becoming increasingly evident. Studies of early life stress have revealed that the microbiome is vital for physiological homeostasis, including diverse aspects of brain function. Intriguingly, caecal transplant from hypertensive rats into normotensive controls induces hypertension similar to that of the donor animals1. We hypothesise that disruption of the microbiota-brain axis will result in cardiorespiratory maladaptation. To test this hypothesis, chronic administration of antibiotics was used to assess the effects of microbiota depletion on cardiorespiratory homeostasis. Eight-week old male Sprague Dawley rats (n=18) were studied. Animals were assigned to sham (normal water, n=10) and chronic antibiotic treatment (ABX, n=8) groups (cocktail of ampicillin (1g/L), vancomycin (500mg/L), ciprofloxacin HCL (20mg/L), imipenem (250mg/L) and metronidazole (1g/L)) for a period of 4 weeks. Animals were weighed daily and faeces collected for microbial diversity assessment. Under urethane anaesthesia (1.5g/kg i.p.), cardiorespiratory assessments were performed. Data are reported as mean±SD and were statistically compared by two-tailed unpaired Student t-test. Disruption of gut physiology was confirmed by enlargement of the caecum in ABX animals compared with sham animals (1.1±0.4 vs 5.1±0.6g/100g; p<0.001). Cardiac right (57.7±6.3 vs 51.1±3.0mg/100g; p=0.011) and left ventricular mass (219.4±14.1 vs 206.7±10.2mg/100g; p=0.04) were reduced in ABX animals and haematocrit concentration was decreased compared with sham controls (51.9±0.9 vs 47.9±0.7%; p=0.004). ABX induced tachypnoea (92±8 vs 107±7bpm; p=0.015), with no significant change in minute ventilation (VE; p=0.225). Systolic blood pressure was reduced in ABX animals (148±15 vs 119±12mmHg; p<0.001). No significant changes in heart rate (p=0.845), diastolic blood pressure (p=0.835), mean arterial blood pressure (p=0.598) or left ventricular contractility (dP/dTMAX; p=0.755) were found when compared with sham treatment. Cervical vagotomy (n=5 per group) produced a greater bradypnoea in ABX animals compared with sham controls (-35±5 vs -48±10bpm; p=0.03). Vagotomy produced equivalent outcomes in measured cardiovascular parameters comparing sham and ABX groups (p>0.05). Given that chronic antibiotic treatment has been shown to dramatically alter the gut microbiome this study demonstrates that microbiota composition changes have significant effects on the cardiorespiratory system, with decreases in cardiac mass, systolic blood pressure and haematocrit suggestive of the development of cardiac maladaptation.