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Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice

Published:February 24, 2017DOI:https://doi.org/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.

      Keywords

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      Linked Article

      • Targeting the Microbiome for Mental Health: Hype or Hope?
        Biological PsychiatryVol. 82Issue 7
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          In the past decade, the microbiota-gut-brain axis has moved to the forefront of neuroscience and psychiatry research. Curiosity about how our bacteria influence health and disease is not limited to scientists and the medical community; the public and the media are completely engaged—it would be difficult to find a stakeholder group related to mental health that has not jumped on the bandwagon. The momentum has been driven primarily by studies in animal models. Evidence is accumulating to show that microbiota influence brain function and behavior, particularly brain systems related to mood and emotions (1).
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