Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice
Burokas, Aurelijus; Arboleya, Silvia; Moloney, Rachel D.; Peterson, Veronica L.; Murphy, Kiera; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.
Date:
2017-02-24
Copyright:
© 2017, Society of Biological Psychiatry. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Full text restriction information:
Access to this article is restricted until 12 months after publication by request of the publisher.
Restriction lift date:
2018-02-24
Citation:
Burokas, A., Arboleya, S., Moloney, R. D., Peterson, V. L., Murphy, K., Clarke, G., Stanton, C., Dinan, T. G. and Cryan, J. F. (2017) ‘Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice’, Biological Psychiatry, 82(7), 472-487. doi:10.1016/j.biopsych.2016.12.031
Abstract:
Background: The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. Methods: C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Results: Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Conclusions: Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology.
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