Imperial College London
Alternate

ProfessorElaineHolmes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wei:2021:10.1073/pnas.2021091118,
author = {Wei, GZ and Martin, KA and Xing, PY and Agrawal, R and Whiley, L and Wood, TK and Hejndorf, S and Ng, YZ and Low, JZY and Rossant, J and Nechanitzky, R and Holmes, E and Nicholson, JK and Tan, E-K and Matthews, PM and Pettersson, S},
doi = {10.1073/pnas.2021091118},
journal = {Proceedings of the National Academy of Sciences},
pages = {1--10},
title = {Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor},
url = {http://dx.doi.org/10.1073/pnas.2021091118},
volume = {118},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Wei,GZ
AU  - Martin,KA
AU  - Xing,PY
AU  - Agrawal,R
AU  - Whiley,L
AU  - Wood,TK
AU  - Hejndorf,S
AU  - Ng,YZ
AU  - Low,JZY
AU  - Rossant,J
AU  - Nechanitzky,R
AU  - Holmes,E
AU  - Nicholson,JK
AU  - Tan,E-K
AU  - Matthews,PM
AU  - Pettersson,S
DO  - 10.1073/pnas.2021091118
EP  - 10
PY  - 2021///
SN  - 0027-8424
SP  - 1
TI  - Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor
T2  - Proceedings of the National Academy of Sciences
UR  - http://dx.doi.org/10.1073/pnas.2021091118
UR  - https://www.pnas.org/content/118/27/e2021091118
UR  - http://hdl.handle.net/10044/1/90111
VL  - 118
ER  -
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