Department of Neurobiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Nat Cell Biol. 2024 Jan;26(1):72-85. doi: 10.1038/s41556-023-01299-2. Epub 2024 Jan 2.
A growing body of evidence indicates that gut microbiota influence brain function and behaviour. However, the molecular basis of how gut bacteria modulate host nervous system function is largely unknown. Here we show that vitamin B-producing bacteria that colonize the intestine can modulate excitatory cholinergic signalling and behaviour in the host Caenorhabditis elegans. Here we demonstrate that vitamin B reduces cholinergic signalling in the nervous system through rewiring of the methionine (Met)/S-adenosylmethionine cycle in the intestine. We identify a conserved metabolic crosstalk between the methionine/S-adenosylmethionine cycle and the choline-oxidation pathway. In addition, we show that metabolic rewiring of these pathways by vitamin B reduces cholinergic signalling by limiting the availability of free choline required by neurons to synthesize acetylcholine. Our study reveals a gut-brain communication pathway by which enteric bacteria modulate host behaviour and may affect neurological health.
越来越多的证据表明,肠道微生物群会影响大脑功能和行为。然而,肠道细菌调节宿主神经系统功能的分子基础在很大程度上尚不清楚。在这里,我们发现定植于肠道的产维生素 B 细菌可以调节宿主秀丽隐杆线虫的兴奋性胆碱能信号传递和行为。在这里,我们证明维生素 B 通过重新布线肠道中的蛋氨酸(Met)/S-腺苷甲硫氨酸循环来降低神经系统中的胆碱能信号传递。我们确定了蛋氨酸/S-腺苷甲硫氨酸循环和胆碱氧化途径之间保守的代谢串扰。此外,我们还表明,维生素 B 对这些途径的代谢重排通过限制神经元合成乙酰胆碱所需的游离胆碱的可用性来降低胆碱能信号传递。我们的研究揭示了一种肠道-大脑通讯途径,其中肠道细菌可以调节宿主行为,并可能影响神经健康。