Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood
Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood
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DOI：
10.1016/j.bbi.2016.07.145
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发表时间：
2017-01-01
影响因子：
15.1
通讯作者：
Stanton, Catherine
中科院分区：
文献类型：
--
作者：
Robertson, Ruairi C.;Oriach, Clara Seira;Stanton, Catherine
背景：神经发育受母体和产后早期饮食的强烈影响。Omega-3多不饱和脂肪酸（n-3 PUFA）是发育中的大脑的重要结构和功能成分。肠道微生物群也受到n-3 PUFA状态的影响，然而，关于母体和早期n-3 PUFA摄入量对后代肠道微生物群发育的作用以及随后与中枢神经系统功能和行为结果的相互作用，我们知之甚少。方法：采用对照（CON）、omega-3缺乏（O3-）和omega-3补充（O3+）三种饲料喂养妊娠雌性C57BL/6小鼠及其雄性后代。通过对青春期（第4-5周）和成年期（第11-13周）的雄性后代进行一系列行为测试来评估认知、抑郁和社会行为。通过分析应激诱导的皮质酮生成来评估下丘脑-垂体-肾上腺轴（HPA）的激活。通过165测序分析了青少年和成年期的粪便微生物群组成。此外，还评估了受刺激的脾脏细胞因子水平。结果：n-3 PUFA干预引起了子代早期和青春期行为的微妙变化，这种变化在成年期进一步明显，例如O3-动物表现出沟通、社交和抑郁相关行为的障碍，而O3+动物表现出认知能力的增强。O3-小鼠表现出厚壁菌门：拟杆菌门比例升高和全身LPS反应迟钝。相比之下，O3+小鼠的粪便中双歧杆菌和乳酸杆菌的丰度更高，hpa轴活性受到抑制。结论：与认知、焦虑和社会行为相关的神经行为发育高度依赖于子宫内和终身n-3 PUFA的可用性。此外，n-3 PUFA状态改变引起的神经行为改变与肠道微生物群组成、hpa轴活性和炎症的全面改变密切相关。(C) 2016 Elsevier Inc.版权所有。
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 165 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. (C) 2016 Elsevier Inc. All rights reserved.