Browsing by Author "Vicentini, Fernando Augusto"

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    Characterization of Bacterial Depletion and Colitis-Associated Changes in the Gut Microbiota on Behaviour and Intestinal Physiology
    (2021-05-10) Vicentini, Fernando Augusto; Sharkey, Keith Alexander; Hirota, Simon Andrew; Pittman, Quentin Jerome; McCafferty, Donna-Marie; DeVinney, Rebekah; Gareau, Melanie
    The role of the microbiota in modulating host physiology is now widely accepted. Acting via the microbiota-gut-brain (MGB) axis, intestinal bacteria have been associated with the regulation of gastrointestinal tract and the central nervous system function, in both physiological and pathophysiological conditions, such as in inflammatory bowel disease (IBD). Patients with IBD have an increased incidence of anxiety and depression, which is accompanied by alterations in the microbiota composition. However, the link between changes in microbiota composition and behavioural abnormalities in the context of intestinal inflammation is unknown. Mechanisms that mediate the MGB axis in homeostasis have emerged but are still incomplete. We sought to characterize the effects of bacterial depletion on intestinal physiology and animal behaviour, and the role of colitis-associated microbiota in the modulation of behavioural abnormalities. Using mouse models of bacterial depletion (antibiotic treatment) and colitis (administration of dextran sulfate sodium), we investigated the role of the microbiota in intestinal physiology and behavioural outputs, and the potential mechanisms of these interactions. The major findings were: (1) bacterial depletion induced a reduction in despair behaviour in a sex-specific manner. The altered behaviour observed in male mice was normalized by activation of the Aryl hydrocarbon receptor, suggesting that this receptor is involved in modulation of behaviour via host-microbe interactions. (2) Bacterial depletion was linked to sex-independent changes in intestinal physiology, including reduced motility, altered secretion, and increased permeability. These changes were accompanied by a reduction in the numbers of enteric neurons, suggesting that microbiota influences the enteric nervous system integrity. Administration of bacterial-derived molecules, lipopolysaccharide and short-chain fatty acids, was associated with neuronal survival and neurogenesis, respectively. (3) Colitis induced changes in the intestinal bacteria composition, which was associated with behavioural abnormalities. Microbiota transfer of colitis-associated microbiota into recipient healthy mice was sufficient to induce behavioural alterations. Remarkably, no intestinal or neuroinflammation were observed in recipient mice. Collectively, these findings provide support to expand our understanding of the MGB axis under homeostatic and intestinal inflammatory conditions. Thus, a better understanding of this integrated network provides a rationale for the development of microbiota-centred therapeutic approaches for the improvement of health.