title: Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.
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.
authors.affiliation: APC Microbiome Institute, University College Cork, Cork.
authors.forename: Aurelijus
authors.initials: A
authors.lastname: Burokas
authors.affiliation: APC Microbiome Institute, University College Cork, Cork; Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Ireland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arboleya
authors.affiliation: APC Microbiome Institute, University College Cork, Cork.
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Moloney
authors.affiliation: APC Microbiome Institute, University College Cork, Cork; Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork; Department of Anatomy and Neuroscience, University College Cork, Cork.
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Peterson
authors.affiliation: Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Ireland.
authors.forename: Kiera
authors.initials: K
authors.lastname: Murphy
authors.affiliation: APC Microbiome Institute, University College Cork, Cork.
authors.forename: Gerard
authors.initials: G
authors.lastname: Clarke
authors.affiliation: APC Microbiome Institute, University College Cork, Cork; Teagasc Food Research Centre, Biosciences Department, Moorepark, Fermoy, Ireland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Stanton
authors.affiliation: APC Microbiome Institute, University College Cork, Cork.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.affiliation: APC Microbiome Institute, University College Cork, Cork; Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork; Department of Anatomy and Neuroscience, University College Cork, Cork. Electronic address: j.cryan@ucc.ie.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000097:blood / Q000209:etiology / Q000628:therapy*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000097:blood; D059225:Nociception / Q000187:drug effects; D009844:Oligosaccharides / Q000627:therapeutic use*; D056692:Prebiotics; D013315:Stress, Psychological / Q000150:complications; D014364:Tryptophan / Q000097:blood
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D009844:Oligosaccharides; D056692:Prebiotics; D014364:Tryptophan; D003345:Corticosterone
keywords: Animal behavior; Anxiety; Microbiota-gut-brain axis; Prebiotics; SCFAs; Stress