Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice
Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice
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DOI：
10.1016/j.biopsych.2016.12.031
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发表时间：
2017-10-01
影响因子：
10.6
通讯作者：
Cryan, John F.
中科院分区：
文献类型：
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作者：
Burokas, Aurelijus;Arboleya, Silvia;Cryan, John F.
背景技术背景：微生物群-肠-脑轴在健康和疾病（包括神经精神疾病）中起着关键作用，这一认识正在迅速发展。用益生元（如低聚果糖（FOS）和低聚半乳糖（GOS））培育有益的肠道微生物组是一种有吸引力但研究不足的微生物群操纵。在这里，我们测试了是否慢性益生元治疗修改跨域相关的焦虑，抑郁，认知，应激反应，和social behavior.METHODS：C57 BL/6 J雄性小鼠给予FOS，GOS，或组合的FOS 1GOS 3周前测试。测量血浆皮质酮、微生物群组成和盲肠短链脂肪酸。此外，FOS 1GOS或水处理的小鼠也暴露于慢性心理社会应激，行为，免疫和微生物群参数进行了assessed.RESULTS：慢性益生元FOS 1GOS治疗表现出抗抑郁和抗焦虑的作用。此外，GOS和FOS 1GOS组合的施用减少了应激诱导的皮质酮释放。益生元修饰海马和下丘脑中的特定基因表达。关于短链脂肪酸浓度，益生元给药增加了盲肠乙酸和丙酸，降低了异丁酸浓度，这些变化与对行为的积极影响显著相关。此外，FOS 1GOS减少慢性应激诱导的皮质酮和促炎细胞因子水平升高和抑郁样和焦虑样行为，除了正常化的压力对microbiota.CONCLUSIONS的影响：两者合计，这些数据强烈表明益生元治疗的有益作用，压力相关的行为。这些发现加强了支持针对脑-肠轴疾病的肠道微生物群治疗的证据基础，为营养神经精神药理学领域开辟了新的途径。
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 FOS1GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS1GOS-or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed.RESULTS: Chronic prebiotic FOS1GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS1GOS 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, FOS1GOS 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.