Drug Design & Development Section, Translational Gerontology Branch, Biomedical Research Center, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Drug Design & Development Section, Translational Gerontology Branch, Biomedical Research Center, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
Trends Neurosci. 2019 Mar;42(3):151-163. doi: 10.1016/j.tins.2018.12.005. Epub 2019 Feb 19.
From an evolutionary perspective, the genes of enteric microbes transmitted reliably across generations are nearly as much a part of the human organism as our own genes. Disruption of the microbiome leading to extinction of key 'heirloom' taxa can deprive individuals of metabolic pathways that have been present in their ancestors for millennia. Some of these pathways support essential synthesis and toxin clearance processes, including the generation of blood-brain barrier-crossing metabolic products crucial for normal brain function. Here, we discuss three such pathways: endogenous benzodiazepine synthesis, production of queuine/queuosine, and excretion of dietary mercury. Among them, these pathways have the potential to impact systems relevant to a wide range of neurodevelopmental and psychiatric conditions including autism, depression, anxiety, and schizophrenia.
从进化的角度来看,能够在代际间可靠传递的肠道微生物的基因几乎和我们自己的基因一样,是人体组织的一部分。肠道微生物组的破坏导致关键的“传家宝”分类群灭绝,可能使个体失去数千年来存在于其祖先中的代谢途径。其中一些途径支持必需的合成和毒素清除过程,包括生成对正常大脑功能至关重要的血脑屏障穿透代谢产物。在这里,我们讨论了其中三种途径:内源性苯二氮䓬合成、鸟苷/假尿嘧啶核苷的产生和膳食汞的排泄。其中,这些途径有可能影响与自闭症、抑郁症、焦虑症和精神分裂症等广泛的神经发育和精神疾病相关的系统。