Hulme, H. et al. (2020) Microbiome-derived carnitine mimics as novel mediators of gut-brain axis communication. Science Advances, 6(11), eaax6328. (doi: 10.1126/sciadv.aax6328) (PMID:32195337) (PMCID:PMC7065903)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Additional Information: | Funding: This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC)–CASE studentship part funded by AstraZeneca (to R.B., D.M.W., and R.J.A.G.) and BBSRC grants BB/K008005/1 and BB/P003281/1 (to D.M.W.). E.K.O. was supported by a Wellcome Trust/Royal Society Sir Henry Dale fellowship 104116/Z/14/Z. S.T. was supported by the Cancer Research UK (C596/A17196, award 23982). J.M.E. was funded by the Multiple Sclerosis Society UK (Grant Ref 38). The Manchester Gnotobiotic Facility was established with the support of the Wellcome Trust (097820/Z/11/B). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Walker, Professor Daniel and Burchmore, Dr Richard and Tardito, Dr Saverio and Edgar, Professor Julia and Ormsby, Dr Michael and Wall, Dr Daniel and Milling, Professor Simon and Van Der Hooft, Mr Justin and Meikle, Dr Lynsey and HULME, Heather and Douce, Dr Gillian and Goodwin, Dr Richard and Kamat, Miss Maya |
| Authors: | Hulme, H., Meikle, L. M., Strittmatter, N., van der Hooft, J. J.J., Swales, J., Bragg, R. A., Villar, V. H., Ormsby, M. J., Barnes, S., Brown, S. L., Dexter, A., Kamat, M. T., Komen, J. C., Walker, D., Milling, S., Osterweil, E. K., MacDonald, A. S., Schofield, C. J., Tardito, S., Bunch, J., Douce, G., Edgar, J. M., Edrada-Ebel, R., Goodwin, R. J.A., Burchmore, R., and Wall, D. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Science Advances |
| Publisher: | American Association for the Advancement of Science |
| ISSN: | 2375-2548 |
| ISSN (Online): | 2375-2548 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Science Advances 6(11):eaax6328 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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