Department of Biomedical Sciences and Imaging, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, PACT Room 400.7S, 116 N Robertson Blvd, Los Angeles, CA, 90048, USA.
Department of Medicine, University of California, Los Angeles, CA, USA.
Psychopharmacology (Berl). 2019 May;236(5):1641-1651. doi: 10.1007/s00213-018-5161-8. Epub 2019 Jan 2.
Recently, there has been a surge of interest in the possibility that microbial communities inhabiting the human gut could affect cognitive development and increase risk for mental illness via the "microbiome-gut-brain axis." Infancy likely represents a critical period for the establishment of these relationships, as it is the most dynamic stage of postnatal brain development and a key period in the maturation of the microbiome. Indeed, recent reports indicate that characteristics of the infant gut microbiome are associated with both temperament and cognitive performance. The neural circuits underlying these relationships have not yet been delineated. To address this gap, resting-state fMRI scans were acquired from 39 1-year-old human infants who had provided fecal samples for identification and relative quantification of bacterial taxa. Measures of alpha diversity were generated and tested for associations with measures of functional connectivity. Primary analyses focused on the amygdala as manipulation of the gut microbiota in animal models alters the structure and neurochemistry of this brain region. Secondary analyses explored functional connectivity of nine canonical resting-state functional networks. Alpha diversity was significantly associated with functional connectivity between the amygdala and thalamus and between the anterior cingulate cortex and anterior insula. These regions play an important role in processing/responding to threat. Alpha diversity was also associated with functional connectivity between the supplementary motor area (SMA, representing the sensorimotor network) and the inferior parietal lobule (IPL). Importantly, SMA-IPL connectivity also related to cognitive outcomes at 2 years of age, suggesting a potential pathway linking gut microbiome diversity and cognitive outcomes during infancy. These results provide exciting new insights into the gut-brain axis during early human development and should stimulate further studies into whether microbiome-associated changes in brain circuitry influence later risk for psychopathology.
最近，人们对这样一种可能性产生了浓厚的兴趣，即人类肠道中栖息的微生物群落可能通过“微生物群-肠道-大脑轴”影响认知发育并增加精神疾病的风险。婴儿期可能代表了建立这些关系的关键时期，因为它是出生后大脑发育最具活力的阶段，也是微生物组成熟的关键时期。事实上，最近的报告表明，婴儿肠道微生物组的特征与气质和认知表现都有关。这些关系的神经回路尚未被描绘出来。为了解决这一差距，从 39 名 1 岁的人类婴儿那里采集了静息态 fMRI 扫描数据，这些婴儿提供了粪便样本，用于鉴定和相对定量细菌分类群。生成了 alpha 多样性的衡量标准，并对其与功能连接性的衡量标准进行了关联测试。主要分析集中在杏仁核上，因为动物模型中肠道微生物群的操纵会改变这个大脑区域的结构和神经化学。二次分析探索了九个典型静息态功能网络的功能连接。alpha 多样性与杏仁核与丘脑之间以及前扣带皮层与前岛叶之间的功能连接显著相关。这些区域在处理/响应威胁方面起着重要作用。alpha 多样性也与运动前区（SMA，代表感觉运动网络）和下顶叶（IPL）之间的功能连接相关。重要的是，SMA-IPL 连接也与 2 岁时的认知结果相关，这表明在婴儿期，肠道微生物组多样性和认知结果之间存在潜在的联系途径。这些结果为人类早期发育过程中的肠道-大脑轴提供了令人兴奋的新见解，应该会刺激进一步研究微生物组相关的大脑回路变化是否会影响后期精神病理学风险。
