Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB014

Poster Communications

Microbiota and respiratory control: Blunted ventilatory responsiveness to hypercapnia in adult male rats following chronic antibiotic treatment

K. M. O'Connor1,2, D. P. Burns1, E. F. Lucking1, A. V. Golubeva2, J. F. Cryan2, K. D. O' Halloran1,3

1. Physiology, School of Medicine, University College Cork, Cork, Ireland. 2. Anatomy and Neuroscience and APC Microbiome Institute, University College Cork, Cork, Ireland. 3. APC Microbiome Institute, University College Cork, Cork, Ireland.

Studies of early life stress models and germ free animals, amongst other experimental models, have revealed that the microbiome is vital for physiological homeostasis, including diverse aspects of brain function. We previously demonstrated in rats that early life stress results in disordered breathing and impaired ventilatory responsiveness, which persists into adulthood, effects that correlate with concomitant alterations in gut microbiota. We sought to further explore the putative link between altered microbiota and respiratory control using chronic antibiotic treatment (ABX) to disrupt the adult microbiome. Forty adult male Sprague Dawley rats were studied. To deplete the microbiota, rats (n=20) were treated with an antibiotic cocktail for 4 weeks beginning at 8 weeks of age, consisting of ampicilin (1g/L), vancomycin (500mg/L), ciprofloxacin HCL (20mg/L), imipenem (250mg/L) and metrondiazol (1g/L) prepared in autoclaved deionised water, changed every 2 days. Sham animals (n=20) received autoclaved deionised water. Animal weights were taken daily. Cages were cleaned every second day. Half the animals in each group were studied after 4 weeks; following a washout period of 72 hours, the remaining animals in both groups received transplantation by oral gavage of control faeces and transfer to sham bedding for a period of 4 weeks in an effort to re-colonize with standard microbiota. Ventilation and metabolism during air breathing and in response to hypercapnic (5% CO2) gas challenge were assessed by whole-body plethysmography. Data are reported as mean ± SD and were compared by unpaired t-test. Baseline ventilation (VE) in rats was unaffected by ABX (0.49 ± 0.07 ml/min/g) compared with WT (0.50 ± 0.06); resting metabolism (VCO2 production) was not different between the two groups (0.018 ± 0.002 versus 0.016 ± 0.003 ml/min/g). Ventilatory responsiveness to hypercapnia was blunted in ABX animals. Thus, VE/VCO2 was lower (p= 0.038) during 5% CO2; mean VE/VCO2 in hypercapnia was (90.6 ± 30.2) versus (66.5 ± 17.4). The blunted response to hypercapnia related to significant depression of the respiratory frequency response to chemostimulation. Baseline ventilation and ventilation during hypercapnic exposure were not different in control re-colonized and ABX re-colonized animals. ABX has been shown to dramatically alter the gut microbiome, with associated changes in mood and cognition. Here we show that ABX blunts ventilatory responsiveness to hypercapnic chemostimulation, suggestive of altered reflex control of breathing. Blunted ventilatory responses to classical activation of chemoreceptors suggests aberrant plasticity in sensory pathways key to the maintenance of respiratory homeostasis.

Where applicable, experiments conform with Society ethical requirements