In mice and humans, the growth and development of the infant brain during the early postnatal period occurs alongside the development of the gut microbiota and it seems there could be an interdependence between these processes. Besides this, omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential structural and functional components of the developing brain. Although the first 3 years of life (of humans) purportedly represent the most critical period for dietary interventions aimed at microbiota modulation to positively affect health later in life, little is known about the relationship between maternal and early-life n-3 PUFA intake and offspring gut microbiota development and subsequent interactions with behavioural outcomes.
A recent study, led by Dr. Catherine Stanton from the Teagasc Moorepark Food Research Centre and APC Microbiome Institute from the University College Cork in Cork (Ireland), has found that neurobehavioural changes induced by altering n-3 PUFA status are closely linked to alterations in gut microbiota composition and inflammation in mice.
The researchers examined the effects of in utero and early life n-3 deficiency or supplementation on depressive, cognitive and social behaviours during adolescence and adulthood in mice, and examined correlations with inflammatory outcomes, HPA-axis activity and alterations to gut microbiota development. Regarding methodology, pregnant female mice and their subsequent male offspring were fed a control standard chow, an omega-3 deficient diet, or an omega-3 supplemented diet (1 g Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) from microalgal oil/100g 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. Faecal microbiota composition was analysed by 16S sequencing in both adolescence and adulthood. In addition, stimulated spleen cytokine levels were assessed.
Although n-3 PUFA interventions induced behavioural changes in both adolescence and adulthood, they were more evident in adulthood. Adult mice that had been fed the omega-3 deficient diet displayed impaired communication and social behaviours, as well as depression-related behaviours, whereas adult mice that were fed the omega-3 supplemented diet displayed enhanced cognition.
Omega-3 dietary intervention had effects on spleen cytokine production after stimulation with Concavalin A (ConA) and lipopolysaccharide (LPS). The omega-3 deficient diet caused significantly decreased spleen levels of tumor necrosis factor (TNFa) and interleukin 10 (IL-10) after stimulation with ConA compared to controls. Moreover, the omega-3 deficient diet significantly decreased spleen levels of TNFa after stimulation with LPS in comparison to the control group.
Neurobehavioural changes induced by the omega-3 supplemented and deficient diets were closely associated with wide ranging compositional changes in the developing gut microbiota. Mice fed with the omega-3 deficient diet displayed an elevated Firmicutes:Bacteroidetes ratio and blunted systemic lipopolysaccharide (LPS) responsiveness. By contrast, mice fed with the omega-3 supplemented diet displayed greater faecal Bifidobacterium and Lactobacillus abundance, which became strengthened in adulthood, and dampened HPA-axis activity under stressful conditions. These results show that dietary intervention, in particular with n-3 PUFA, may have an impact on behavioural outcomes and it could be mediated by the gut-microbiota-brain axis.
To sum up, mouse neurobehavioural changes observed in adolescence and adulthood induced by continued supplementation with, or deficiency of, n-3 fatty acids were closely linked with wide-ranging alterations in gut microbiota composition, HPA-axis activity and inflammation. These data suggest that behavioural outcomes triggered by altered early-life n-3 PUFA status may relate to changes in the gut microbiota.
Robertson RC, Seira Oriach C, Murphy K, et al. Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav Immun. 2016. doi: 10.1016/j.bbi.2016.07.145.