Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes

IF 8.8 2区 医学 Q1 IMMUNOLOGY Brain, Behavior, and Immunity Pub Date : 2024-10-28 DOI:10.1016/j.bbi.2024.10.030
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Abstract

The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.
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自闭症临床前母体免疫激活模型的肠道微生物群转移足以诱导免疫反应和行为结果的性别特异性改变。
肠道微生物群在健康和疾病(包括自闭症谱系障碍(ASD)等神经发育障碍)中发挥着至关重要的作用。自闭症谱系障碍的男女患病比例为 4:1,自闭症谱系障碍患者的肠道微生物群组成以及该疾病的动物模型(如母体免疫激活(MIA)小鼠模型)中都存在明显的性别差异。然而,在评估肠道微生物群在介导 ASD 症状中的作用时,很少有研究将性别作为一个生物变量。我们利用 MIA ASD 模型评估了肠道微生物群是否会导致 ASD 类行为表现的性别差异。我们将来自 MIA 或载体/对照组的雄性和雌性小鼠的肠道微生物群移植到健康、未受其他操纵的 4 周大 C57Bl/6 小鼠体内,共进行了 6 次处理,历时 12 天。雄性(而非雌性)MIA 微生物群的定植足以降低小鼠的交际能力、减少微生物群的多样性并增加神经炎症,雄性受体的缺陷更为明显。雄性和雌性供体微生物群的定植改变了两性受体的幼年超声波发声和焦虑样行为,所有MIA肠道微生物群受体的肠道微生物群和血清细胞因子IL-4和IL-7水平也随之发生了变化。除了与病理状态相关的肠道微生物增加外,女性供体微生物群谱中具有已知神经保护作用的肠道微生物(如乳酸杆菌和利肯菌)也增加了。这些结果表明,肠道对环境损伤的反应性(如在 MIA 模型中)可能在形成 ASD 发展过程中的性别差异方面起了作用。
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来源期刊
CiteScore
29.60
自引率
2.00%
发文量
290
审稿时长
28 days
期刊介绍: Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.
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