Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult ratsResearch in context
Karen M. O'Connor,
Eric F. Lucking,
Anna V. Golubeva,
Conall R. Strain,
Fiona Fouhy,
María C. Cenit,
Pardeep Dhaliwal,
Thomaz F.S. Bastiaanssen,
David P. Burns,
Catherine Stanton,
Gerard Clarke,
John F. Cryan,
Ken D. O'Halloran
Affiliations
Karen M. O'Connor
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
Eric F. Lucking
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland
Anna V. Golubeva
APC Microbiome Ireland, University College Cork, Cork, Ireland
Conall R. Strain
Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
Fiona Fouhy
APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
María C. Cenit
Department of Anatomy & Neuroscience, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; Institute of Agrochemistry and Food Technology (IATA), National Council for Scientific Research (CSIC), Valencia, Spain
Pardeep Dhaliwal
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland
Thomaz F.S. Bastiaanssen
Department of Anatomy & Neuroscience, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
David P. Burns
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland
Catherine Stanton
APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
Gerard Clarke
APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland
John F. Cryan
Department of Anatomy & Neuroscience, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
Ken D. O'Halloran
Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland; Corresponding author at: Department of Physiology, University College Cork, Western Gateway Building, Western Road, Cork, Ireland.
Background: It is increasingly evident that perturbations to the diversity and composition of the gut microbiota have significant consequences for the regulation of integrative physiological systems. There is growing interest in the potential contribution of microbiota-gut-brain signalling to cardiorespiratory control in health and disease. Methods: In adult male rats, we sought to determine the cardiorespiratory effects of manipulation of the gut microbiota following a 4-week administration of a cocktail of antibiotics. We subsequently explored the effects of administration of faecal microbiota from pooled control (vehicle) rat faeces, given by gavage to vehicle- and antibiotic-treated rats. Findings: Antibiotic intervention depressed the ventilatory response to hypercapnic stress in conscious animals, owing to a reduction in the respiratory frequency response to carbon dioxide. Baseline frequency, respiratory timing variability, and the expression of apnoeas and sighs were normal. Microbiota-depleted rats had decreased systolic blood pressure. Faecal microbiota transfer to vehicle- and antibiotic-treated animals also disrupted the gut microbiota composition, associated with depressed ventilatory responsiveness to hypercapnia. Chronic antibiotic intervention or faecal microbiota transfer both caused significant disruptions to brainstem monoamine neurochemistry, with increased homovanillic acid:dopamine ratio indicative of increased dopamine turnover, which correlated with the abundance of several bacteria of six different phyla. Interpretation: Chronic antibiotic administration and faecal microbiota transfer disrupt gut microbiota, brainstem monoamine concentrations and the ventilatory response to hypercapnia. We suggest that aberrant microbiota-gut-brain axis signalling has a modulatory influence on respiratory behaviour during hypercapnic stress. Fund: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland. Keywords: Antibiotics, Faecal microbiota transfer, Breathing, Hypercapnia, Cardiovascular, Vagus, Neurochemistry, Intestinal permeability, Microbiota
