Full-length ArticleOmega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood

- Omega-3 deficiency impairs communicative, social and depressive behaviour.
- Omega-3 supplementation enhances cognition and dampens HPA-axis activation.
- Omega-3 availability adjacently regulates inflammation and gut microbiota composition.
- Behaviours associated with varying omega-3 availability may be mediated by microbiota.

BackgroundNeurodevelopment 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.MethodsPregnant 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.Resultsn-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.ConclusionsNeurobehavioural 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.