Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Imaging and data Analytics, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, UK.
Sci Adv. 2020 Mar 11;6(11):eaax6328. doi: 10.1126/sciadv.aax6328. eCollection 2020 Mar.
Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen-free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function.
肠道微生物组的改变与各种神经疾病有关，但因果关系的证据和介导肠道-大脑轴相互作用的微生物组衍生化合物的身份仍不清楚。在这里，我们鉴定出两种以前未知的细菌代谢物 3-甲基-4-(三甲氨基)丁酸和 4-(三甲氨基)戊酸，它们是肉碱的结构类似物，存在于无特定病原体小鼠的肠道和大脑中，但不存在于无菌小鼠中。我们证明这些化合物是由厌氧共生菌产生的，来自lachnospiraceae 家族(clostridiales)家族，与肉碱在大脑白质中共定位，并在中枢神经系统白质的小鼠细胞培养模型中抑制肉碱介导的脂肪酸氧化。这是首次描述肠道原核生物和哺乳动物脑细胞之间直接的跨王国分子交换，导致脑细胞功能抑制。
