Erschienen:
[Erscheinungsort nicht ermittelbar]: University College Cork, 2019
Sprache:
Englisch
Identifikator:
Entstehung:
Hochschulschrift:
Dissertation, University College Cork, 2019
Anmerkungen:
Beschreibung:
Dysregulated microbiota-gut-brain axis communication adversely influences neurocontrol systems, consequently affecting brain behaviours. It is plausible that microbiota-gut-brain axis signalling has a role in the control of breathing and cardiovascular function, as networks that govern cardiorespiratory control reside within the brainstem, a region innervated by the vagus nerve, a key signalling pathway of the microbiota-gut-brain axis. Cardiovascular and respiratory diseases are serious, potentially life-threatening conditions with limited treatment options. Thus, improved understanding of the underlying pathophysiology and novel therapeutic approaches are required. We performed an assessment of cardiorespiratory physiology in animal models of modified gut microbiota [antibiotic-treated (ABX) and faecal microbiota transfer (FMT)], and sleep-disordered breathing [chronic intermittent hypoxia (CIH)-exposed guinea-pigs and rats]. We investigated if dietary prebiotic supplementation prevented CIH-induced cardiorespiratory dysfunction in rats. Whole-body plethysmography was used to record ventilation and metabolism in unanaesthetised animals during normoxia and chemostimulation. Under anaesthesia, cardiorespiratory assessments were performed during normoxia, chemosensory stimulation and drug administration. Brainstem neurochemistry was assessed by high-performance liquid chromatography. 16S rRNA and whole-metagenome shotgun sequencing was used to characterise the gut microbiota. ABX and FMT disrupted the gut microbiota, brain neurochemistry and intestinal integrity, blunting chemoreflex control of breathing. Decreased brainstem noradrenaline and altered gut microbiota as well as impaired respiratory and autonomic control were evident in CIH-exposed guinea-pigs. CIH–exposed rats developed cardiorespiratory pathologies and decreased gut Lactobacillus rhamnosus relative abundance. Prebiotic administration increased short-chain fatty acid concentrations, measured by gas chromatography, but Lactobacillus rhamnosus and cardiorespiratory dysfunctions were not restored. Several commensal and pathogenic bacterial species correlated with blood pressure parameters. Our findings add to emerging research exploring microbiota-gut-brain signalling in homeostatic systems, extending investigations to cardiorespiratory control. Our studies draw focus to the potential application of manipulation of the gut microbiota as an adjunctive therapy for cardiorespiratory disease.