Microbiome Influences on the neuroendocrine regulation of social behavior

几乎所有的动物，包括人类，都是多种微生物的宿主，如细菌和真菌，它们在细胞、组织和器官中起作用。这些微生物中有许多存在于肠道内。最近的证据表明，这种“肠道微生物群”对成年人和年轻人的正常大脑和行为产生了惊人而强大的影响。然而，肠道微生物群如何影响大脑和行为，基本上是未知的。本研究将通过关注矮个子仓鼠共享的母代-子代微生物组，来测试肠道微生物组可能促进后代社会性发展的新机制。这项拟议研究的目的是测试这样一种观点，即通过抗生素治疗破坏母体微生物群，改变母体肠道微生物群的多样性和组成，从而影响其后代正常社会行为和相关生理参数的发展。这项研究还将测试母体肠道微生物群的恢复是否会使社会行为恢复正常。最后，这些研究将检验双亲（即母亲和父亲）行为在预防母体微生物群破坏对后代社会行为的不利影响方面的作用。总的来说，这些研究将为母体微生物组影响后代社会性发展的基本机制提供基础知识。了解这些机制将提供重要的基础知识，可能最终为以社会功能缺陷为特征的衰弱性疾病的治疗和预防提供信息。除了培训研究生研究人员外，印第安纳大学本科生研究经验项目的本科生以及当地的中学教师和中学班级将参与研究。中学生们将在当地的大理石山农场参加以土壤和肠道微生物为重点的活动。然而，微生物组对大脑和社会行为影响的确切生理机制仍不清楚。本研究采用动物模型来阐明母体微生物组状态对后代社会性发育的影响，以及观察到的微生物组-脑-行为关系的机制。具体来说，实验利用表现出双亲（即母亲和父亲）照顾或单亲（即完全母亲）照顾的动物来梳理它们对后代发育的相对贡献。本研究的目的是验证以下假设：1)通过抗生素给药破坏母体微生物群会改变肠道微生物群的多样性和组成，从而改变后代的社会性、应激反应性和细胞因子谱；2)神经内分泌和/或神经免疫系统的破坏至少部分地介导了对社会行为的影响；3)通过粪便移植来补充肠道微生物群可以恢复正常的社会行为；4)双亲抚育通过提供额外的父亲行为来缓冲后代来调节这些影响。这些研究将为以下方面提供有价值的见解：微生物组影响母代行为相互作用的基本机制，父亲行为在缓冲母亲微生物组破坏对后代行为的影响中的作用，以及更广泛的社会行为的发展。

Virtually all animals, including humans, play host to a wide range of microorganisms such as bacteria and fungi that function within cells, tissues, and organs. Many of these microorganisms reside within the gut. Recent evidence suggests that this 'gut microbiome' exerts a surprising and powerful influence on the normal brain and on behavior in both adults and the young. How the gut microbiome influences the brain and behavior, however, is essentially unknown. This research will test a novel mechanism by which the gut microbiome may contribute to the development of offspring sociality by focusing on the shared mother-offspring microbiome in dwarf hamsters. The goal of the proposed research is to test the idea that disruption of the maternal microbiome, via antibiotic administration, alters the diversity and composition of the mother's gut microbiome and consequently affects the development of normal social behavior and related physiological parameters in her offspring. This research will also test whether the restoration of the maternal gut microbiome returns social behaviors to normal. Lastly, these studies will examine the role of bi-parental (i.e., mother and father) behaviors in preventing the adverse effects of a disrupted maternal microbiome on offspring social behavior. Collectively, these studies will provide fundamental knowledge of the basic mechanisms by which the maternal microbiome influences the development of offspring sociality. An understanding of these mechanisms will provide important basic knowledge that may ultimately inform treatment and prevention of debilitating disorders characterized by deficits of social functioning. In addition to training graduate student researchers, undergraduates in Indiana University's Research Experience for Undergraduates program and a local middle school teacher and middle school class will take part in the research. The middle school students will participate in activities focused on soil and gut microbes at the local Marble Hill Farm. The precise physiological mechanisms underlying microbiome effects on the brain and social behavior, however, remain unknown. This research employs an animal model to elucidate the impact of maternal microbiome status on the development of offspring sociality as well as the mechanisms underlying observed microbiome-brain-behavior relationships. Specifically, the experiments utilize animals that display either bi-parental (i.e., both maternal and paternal) care or uni-parental (i.e., exclusively maternal) care to tease apart their relative contributions to offspring development. The goal of the proposed research is to test the specific hypotheses that: 1) disruption of the maternal microbiome via antibiotic administration alters the diversity and composition of gut microbiota and consequently offspring sociality, stress responsivity, and cytokine profiles; 2) disruption of neuroendocrine and/or neuroimmune systems mediates, at least in part, the effects on social behaviors; 3) repletion of the gut microbiome via fecal transplants restores normal social behaviors; and 4) bi-parental care modulates these effects by providing additional contributions of paternal behavior to buffer offspring. The proposed studies will provide valuable insight on the basic mechanisms of microbiome influences on maternal-offspring behavioral interactions, the role of paternal behaviors in buffering the influences of maternal microbiome disruption on offspring behavior, as well as the development of social behaviors more broadly.