Department of Pediatrics, School of Medicine, Washington University in St Louis, Saint Louis, MO, USA.
Pediatr Res. 2019 Jan;85(2):216-224. doi: 10.1038/s41390-018-0191-9. Epub 2018 Sep 25.
Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism. Critical developmental windows that influence early behavioral outcomes have been identified that include both the prenatal environment and early postnatal colonization periods. The clearest data regarding the role of the gut microbiota on neurodevelopment and psychiatric disorders is from animal studies; however, human data have begun to emerge, including an association between early colonization patterns and cognition. The importance of understanding the contribution of the gut microbiota to the development and functioning of the nervous system lies in the potential to intervene using novel microbial-based approaches to treating neurologic conditions. While pathways of communication between the gut and brain are well established, the gut microbiome is a new component of this axis. The way in which organisms that live in the gut influence the central nervous system (CNS) and host behavior is likely to be multifactorial in origin. This includes immunologic, endocrine, and metabolic mechanisms, all of which are pathways used for other microbial-host interactions. Germ-free (GF) mice are an important model system for understanding the impact of gut microbes on development and function of the nervous system. Alternative animal model systems have further clarified the role of the gut microbiota, including antibiotic treatment, fecal transplantation, and selective gut colonization with specific microbial organisms. Recently, researchers have started to examine the human host as well. This review will examine the components of the CNS potentially influenced by the gut microbiota, and the mechanisms mediating these effects. Links between gut microbial colonization patterns and host behavior relevant to a pediatric population will be examined, highlighting important developmental windows in utero or early in development.
肠道和大脑之间的双向交流是众所周知的，现在有数据表明，肠道微生物群在这种联系中起着特定的作用，被称为微生物群-肠道-大脑轴。这篇综述将讨论肠道微生物群在大脑发育和行为中的新作用。动物研究清楚地表明，肠道微生物群对影响行为和表现的基因表达和神经化学代谢有影响。基于这些变化，已经证明了肠道微生物群对各种神经精神疾病的调节作用，包括抑郁症、焦虑症和帕金森病等运动障碍，对儿科人群自闭症尤为重要。已经确定了影响早期行为结果的关键发育窗口期，包括产前环境和早期产后定植期。关于肠道微生物群对神经发育和精神障碍的作用的最明确的数据来自动物研究；然而，人类数据已经开始出现，包括早期定植模式与认知之间的关联。了解肠道微生物群对神经系统发育和功能的贡献的重要性在于，有可能通过使用新型微生物为基础的方法来治疗神经疾病。虽然肠道和大脑之间的通讯途径已经确立，但肠道微生物群是这个轴的一个新组成部分。生活在肠道中的生物体影响中枢神经系统（CNS）和宿主行为的方式很可能是多因素的起源。这包括免疫、内分泌和代谢机制，所有这些都是其他微生物-宿主相互作用的途径。无菌（GF）小鼠是理解肠道微生物对神经系统发育和功能影响的重要模型系统。替代的动物模型系统进一步阐明了肠道微生物群的作用，包括抗生素治疗、粪便移植和特定微生物的选择性肠道定植。最近，研究人员也开始研究人类宿主。这篇综述将检查可能受肠道微生物群影响的中枢神经系统成分，以及介导这些影响的机制。将检查与儿科人群相关的肠道微生物定植模式与宿主行为之间的联系，强调子宫内或早期发育的重要发育窗口期。
