Microbiome Influences on the neuroendocrine regulation of social behavior

微生物组对社会行为神经内分泌调节的影响

• 批准号: 1656414
• 负责人: Gregory Demas
• 金额: $ 60万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656414&HistoricalAwards=false
• 关键词: Microbiome; Influences; neuroendocrine; regulation; social

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.

事实上，包括人类在内的所有动物都是多种微生物的宿主，例如在细胞、组织和器官内发挥作用的细菌和真菌。 许多这些微生物存在于肠道内。最近的证据表明，这种“肠道微生物群”对成人和年轻人的正常大脑以及行为产生令人惊讶和强大的影响。 然而，肠道微生物组如何影响大脑和行为基本上是未知的。这项研究将通过关注侏儒仓鼠中共享的母子微生物组来测试肠道微生物组可能有助于后代社会性发展的新机制。拟议研究的目的是检验这样一种观点：通过抗生素给药破坏母体微生物组，会改变母体肠道微生物组的多样性和组成，从而影响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能让社会行为恢复正常。最后，这些研究将探讨双亲（即母亲和父亲）行为在防止母体微生物组破坏对后代社会行为产生不利影响方面的作用。总的来说，这些研究将提供有关母体微生物组影响后代社会性发展的基本机制的基础知识。 对这些机制的理解将提供重要的基础知识，最终可能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体验项目的本科生以及当地中学教师和中学班级也将参与这项研究。中学生将在当地的大理石山农场参加以土壤和肠道微生物为主题的活动。然而，微生物组对大脑和社会行为影响的确切生理机制仍然未知。 这项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展的影响，以及观察到的微生物组-大脑-行为关系的机制。具体来说，这些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。拟议研究的目的是测试以下具体假设：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，从而改变后代的社交性、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介导对社会行为的影响； 3）通过粪便移植补充肠道微生物组，恢复正常的社会行为； 4）双亲抚育通过提供父亲行为的额外贡献来缓冲后代来调节这些影响。 拟议的研究将为微生物组影响母子行为相互作用的基本机制、父亲行为在缓冲母体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提供有价值的见解。

项目成果

Photoperiod modulates the gut microbiome and aggressive behavior in Siberian hamsters

光周期调节西伯利亚仓鼠的肠道微生物组和攻击行为

• DOI: 10.1242/jeb.212548
• 发表时间: 2020
• 期刊: The Journal of Experimental Biology
• 作者: Ren, Clarissa C.;Sylvia, Kristyn E.;Munley, Kathleen M.;Deyoe, Jessica E.;Henderson, Sarah G.;Vu, Michael P.;Demas, Gregory E.
• 通讯作者: Demas, Gregory E.

Maternal stress and the maternal microbiome have sex-specific effects on offspring development and aggressive behavior in Siberian hamsters (Phodopus sungorus)

• DOI: 10.1016/j.yhbeh.2022.105146
• 发表时间: 2022-03-08
• 期刊: HORMONES AND BEHAVIOR
• 影响因子: 3.5
• 作者: Cusick, Jessica A.;Wellman, Cara L.;Demas, Gregory E.
• 通讯作者: Demas, Gregory E.