气候变化领域集成服务门户(CCPortal): Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

CCPortal

DOI	10.1073/pnas.2021091118
	Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor
	Wei G.Z.; Martin K.A.; Xing P.Y.; Agrawal R.; Whiley L.; Wood T.K.; Hejndorf S.; Ng Y.Z.; Low J.Z.Y.; Rossant J.; Nechanitzky R.; Holmes E.; Nicholson J.K.; Tan E.-K.; Matthews P.M.; Pettersson S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:27
英文摘要	While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR−/−) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Aryl hydrocarbon receptor; Indole; Microbiota; Neurogenesis; Tryptophan metabolism
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238874
作者单位	Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore; National Neuroscience Institute, Singapore, 169857, Singapore; The Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore; Interdisciplinary Graduate School, Nanyang Technological University, Singapore, 637335, Singapore; Australian National Phenome Centre, Health Futures Institute, Murdoch University, Perth, WA 6150, Australia; Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia; Department of Chemical Engineering, Pennsylvania State University, University Park, PA 16802, United States; Department of Neurobiology, Care and Society, Karolinska Institutet, Stockholm, 171 77, Sweden; The School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore; Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learni...
推荐引用方式 GB/T 7714	Wei G.Z.,Martin K.A.,Xing P.Y.,et al. Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor[J],2021,118(27).
APA	Wei G.Z..,Martin K.A..,Xing P.Y..,Agrawal R..,Whiley L..,...&Pettersson S..(2021).Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor.Proceedings of the National Academy of Sciences of the United States of America,118(27).
MLA	Wei G.Z.,et al."Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor".Proceedings of the National Academy of Sciences of the United States of America 118.27(2021).