Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult rats.
Animals
Anti-Bacterial Agents
/ administration & dosage
Biomarkers
Blood Gas Analysis
Brain Stem
/ metabolism
Breath Tests
Cell Membrane Permeability
Disease Models, Animal
Fecal Microbiota Transplantation
Feces
/ microbiology
Gastrointestinal Microbiome
/ drug effects
Heart Function Tests
Heart Rate
Hypercapnia
/ blood
Hypoxia
/ metabolism
Intestinal Mucosa
/ metabolism
Male
Metagenome
Metagenomics
/ methods
Rats
Receptors, Serotonin, 5-HT3
/ metabolism
Respiration
Antibiotics
Breathing
Cardiovascular
Faecal microbiota transfer
Hypercapnia
Intestinal permeability
Microbiota
Neurochemistry
Vagus
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
10
12
2018
revised:
08
03
2019
accepted:
11
03
2019
pubmed:
23
3
2019
medline:
18
12
2019
entrez:
23
3
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 30898652
pii: S2352-3964(19)30169-0
doi: 10.1016/j.ebiom.2019.03.029
pmc: PMC6606895
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Biomarkers
0
Receptors, Serotonin, 5-HT3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
618-638Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019. Published by Elsevier B.V.