Imperial College London
Portrait Picture

Professor Marc-Emmanuel Dumas

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Systems Medicine
 
 
 
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Contact

 

+44 (0)20 7594 1820m.dumas Website

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E315BBurlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Serger:2022:10.1038/s41586-022-04884-x,
author = {Serger, E and Luengo-Gutierrez, L and Chadwick, JS and Kong, G and Zhou, L and Crawford, G and Danzi, MC and Myridakis, A and Brandis, A and Bello, AT and Muller, F and Sanchez-Vassopoulos, A and De, Virgiliis F and Liddell, P and Dumas, ME and Strid, J and Mani, S and Dodd, D and Di, Giovanni S},
doi = {10.1038/s41586-022-04884-x},
journal = {Nature},
pages = {585--592},
title = {The gut metabolite indole-3 propionate promotes nerve regeneration and repair},
url = {http://dx.doi.org/10.1038/s41586-022-04884-x},
volume = {607},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The regenerative potential of mammalian peripheral nervous system neurons after injury is critically limited by their slow axonal regenerative rate1. Regenerative ability is influenced by both injury-dependent and injury-independent mechanisms2. Among the latter, environmental factors such as exercise and environmental enrichment have been shown to affect signalling pathways that promote axonal regeneration3. Several of these pathways, including modifications in gene transcription and protein synthesis, mitochondrial metabolism and the release of neurotrophins, can be activated by intermittent fasting (IF)4,5. However, whether IF influences the axonal regenerative ability remains to be investigated. Here we show that IF promotes axonal regeneration after sciatic nerve crush in mice through an unexpected mechanism that relies on the gram-positive gut microbiome and an increase in the gut bacteria-derived metabolite indole-3-propionic acid (IPA) in the serum. IPA production by Clostridium sporogenes is required for efficient axonal regeneration, and delivery of IPA after sciatic injury significantly enhances axonal regeneration, accelerating the recovery of sensory function. Mechanistically, RNA sequencing analysis from sciatic dorsal root ganglia suggested a role for neutrophil chemotaxis in the IPA-dependent regenerative phenotype, which was confirmed by inhibition of neutrophil chemotaxis. Our results demonstrate the ability of a microbiome-derived metabolite, such as IPA, to facilitate regeneration and functional recovery of sensory axons through an immune-mediated mechanism.
AU  - Serger,E
AU  - Luengo-Gutierrez,L
AU  - Chadwick,JS
AU  - Kong,G
AU  - Zhou,L
AU  - Crawford,G
AU  - Danzi,MC
AU  - Myridakis,A
AU  - Brandis,A
AU  - Bello,AT
AU  - Muller,F
AU  - Sanchez-Vassopoulos,A
AU  - De,Virgiliis F
AU  - Liddell,P
AU  - Dumas,ME
AU  - Strid,J
AU  - Mani,S
AU  - Dodd,D
AU  - Di,Giovanni S
DO  - 10.1038/s41586-022-04884-x
EP  - 592
PY  - 2022///
SN  - 0028-0836
SP  - 585
TI  - The gut metabolite indole-3 propionate promotes nerve regeneration and repair
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-022-04884-x
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000814485100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://www.nature.com/articles/s41586-022-04884-x
VL  - 607
ER  -
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