ABSTRACT

Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut–brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut–brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut–brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein.

Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins

摘要

肠道微生物群组成的改变与一系列神经发育、神经退行性和神经精神疾病有关。肠道微生物转化和代谢源自饮食和宿主的分子，产生具有局部和全身作用的多种代谢物。大脑和肠道微生物之间的双向交流，即所谓的肠-脑轴，由免疫、神经元和内分泌信号通路组成的网络。尽管尚未确定肠-脑串扰的各种机制，但现有数据表明，单一代谢物或其衍生物可能是肠-脑轴通讯中的关键诱导物。然而，

缩写： 4-EPS 4-乙基苯基硫酸盐；5-AVA(B) 5-氨基戊酸（甜菜碱）；Aβ淀粉样β蛋白；AhR芳烃受体；ASD自闭症谱系障碍；BBB 血脑屏障；BDNF 脑源性神经营养因子；CNS 中枢神经系统；GABA ɣ-氨基丁酸；GF 无菌；MIA 母体免疫激活；SCFA 短链脂肪酸；3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(三甲基铵)戊酸酯；TMA(O) 三甲胺( -N-氧化物)；TUDCA 牛磺熊去氧胆酸；ZO Zonula occludens 蛋白