title: Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood.
abstract: BACKGROUND
  Neurodevelopment is strongly influenced by maternal and early-postnatal diet. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are vital structural and functional components of the developing brain. The gut microbiota is also influenced by n-3 PUFA status, however, little is known about the role of maternal and early-life n-3 PUFA intake on offspring gut microbiota development and subsequent interactions with central nervous system functioning and behavioural outcomes.
  
  
  METHODS
  Pregnant female C57BL/6 mice and their male offspring were fed a control (CON), omega-3 deficient (O3-) or omega-3 supplemented (O3+) diet. Cognitive, depressive and social behaviours were assessed through a battery of behaviour tests in the male offspring at both adolescence (week 4-5) and adulthood (week 11-13). Hypothalamic-pituitary-adrenal axis (HPA) activation was assessed by analysis of stress-induced corticosterone production. Fecal microbiota composition was analysed by 16S sequencing at both adolescent and adulthood. In addition, stimulated spleen cytokine levels were assessed.
  
  
  RESULTS
  n-3 PUFA interventions induced subtle changes in offspring early-life and adolescent behaviours, which were further evident in adulthood, such that O3- animals displayed impaired communication, social and depression-related behaviours and O3+ animals displayed enhanced cognition. O3- mice displayed an elevated Firmicutes:Bacteroidetes ratio and blunted systemic LPS responsiveness. Contrastingly, O3+ mice displayed greater fecal Bifidobacterium and Lactobacillus abundance and dampened HPA-axis activity.
  
  
  CONCLUSIONS
  Neurobehavioural development related to cognitive, anxiety and social behaviours, is highly dependent upon in utero and lifelong n-3 PUFA availability. In addition, neurobehavioural changes induced by altering n-3 PUFA status are closely associated with comprehensive alterations in gut microbiota composition, HPA-axis activity and inflammation.
authors.affiliation: School of Microbiology, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Co. Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: Ruairi C
authors.initials: RC
authors.lastname: Robertson
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Ireland.
authors.forename: Clara
authors.initials: C
authors.lastname: Seira Oriach
authors.affiliation: Teagasc Moorepark Food Research Centre, Fermoy, Co. Cork, Ireland.
authors.forename: Kiera
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Department of Anatomy and Neuroscience, University College Cork, Ireland.
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Moloney
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Ireland.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.affiliation: School of Science Engineering and Food Science, University College Cork, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Paul Ross
authors.affiliation: Teagasc Moorepark Food Research Centre, Fermoy, Co. Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Ireland. Electronic address: Catherine.stanton@teagasc.ie.
authors.forename: Catherine
authors.initials: C
authors.lastname: Stanton
mesh_terms: D000375:Aging / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003071:Cognition; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000523:psychology; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000502:physiology*; D005239:Fear; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010913:Pituitary-Adrenal System / Q000502:physiology; D011247:Pregnancy; D021641:Recognition, Psychology; D012919:Social Behavior; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology; D013550:Swimming / Q000523:psychology; D014828:Vocalization, Animal
chemical_list: D016207:Cytokines; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D003345:Corticosterone
keywords: Adolescence; Behaviour; Cognition; Corticosterone; Depression; Diet; Gut-brain axis; Inflammation; Microbiota; Neurodevelopment; Omega-3 polyunsaturated fatty acids; Psychiatric illnesses; Social behaviour