Biological psychiatryMar 1, 2017

Prebiotics may reduce anxiety and depression and counteract chronic stress effects through the gut-brain connection in mice

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 1, 2026

Abstract

Chronic prebiotic treatment with a combination of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) showed antidepressant and anxiolytic effects in male mice.

Prebiotic treatment reduced stress-induced corticosterone release.
Specific gene expression changes were observed in the hippocampus and hypothalamus following prebiotic administration.
Cecal concentrations of acetate and propionate increased, while isobutyrate concentrations decreased with prebiotic treatment, correlating with improved behavior.
FOS+GOS treatment alleviated chronic stress-induced increases in proinflammatory cytokine levels and reduced anxiety-like and depression-like behaviors.
These results suggest prebiotic treatment may beneficially influence stress-related behaviors and gut-brain interactions.

Simplified

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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Prebiotics may reduce anxiety and depression and counteract chronic stress effects through the gut-brain connection in mice

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