Goyal Manu S, Venkatesh Siddarth, Milbrandt Jeffrey, Gordon Jeffrey I, Raichle Marcus E
Neuroimaging Laboratory, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110;
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110; Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110;
Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14105-12. doi: 10.1073/pnas.1511465112.
The human gut contains a microbial community composed of tens of trillions of organisms that normally assemble during the first 2-3 y of postnatal life. We propose that brain development needs to be viewed in the context of the developmental biology of this "microbial organ" and its capacity to metabolize the various diets we consume. We hypothesize that the persistent cognitive abnormalities seen in children with undernutrition are related in part to their persistent gut microbiota immaturity and that specific regions of the brain that normally exhibit persistent juvenile (neotenous) patterns of gene expression, including those critically involved in various higher cognitive functions such as the brain's default mode network, may be particularly vulnerable to the effects of microbiota immaturity in undernourished children. Furthermore, we postulate that understanding the interrelationships between microbiota and brain metabolism in childhood undernutrition could provide insights about responses to injury seen in adults. We discuss approaches that can be used to test these hypotheses, their ramifications for optimizing nutritional recommendations that promote healthy brain development and function, and the potential societal implications of this area of investigation.
人类肠道含有一个由数万亿生物体组成的微生物群落,这些微生物通常在出生后的头2至3年中聚集。我们提出,需要从这个“微生物器官”的发育生物学及其代谢我们所摄入各种饮食的能力的背景下来看待大脑发育。我们假设,营养不良儿童中持续存在的认知异常部分与他们持续的肠道微生物群不成熟有关,并且大脑中通常表现出持续的幼年(幼态持续)基因表达模式的特定区域,包括那些在各种高级认知功能(如大脑默认模式网络)中起关键作用的区域,可能特别容易受到营养不良儿童微生物群不成熟的影响。此外,我们推测,了解儿童期营养不良中微生物群与大脑代谢之间的相互关系,可以为理解成年人对损伤的反应提供见解。我们讨论了可用于检验这些假设的方法、它们对优化促进健康大脑发育和功能的营养建议的影响,以及这一研究领域的潜在社会意义。
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