@article{67b6a159d6b84e5ab9d0ebff3d78f771,
title = "Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication",
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.",
author = "Heather Hulme and Meikle, \{Lynsey M.\} and Nicole Strittmatter and \{van der Hooft\}, \{Justin J.J.\} and John Swales and Bragg, \{Ryan A.\} and Villar, \{Victor H.\} and Ormsby, \{Michael J.\} and Stephanie Barnes and Brown, \{Sheila L.\} and Alex Dexter and Kamat, \{Maya T.\} and Komen, \{Jasper C.\} and Daniel Walker and Simon Milling and Osterweil, \{Emily K.\} and MacDonald, \{Andrew S.\} and Schofield, \{Chris J.\} and Saverio Tardito and Josephine Bunch and Gillian Douce and Edgar, \{Julia M.\} and Edrada-Ebel, \{Ru Angelie\} and Goodwin, \{Richard J.A.\} and Richard Burchmore and Wall, \{Daniel M.\}",
note = "Funding Information: 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). Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2020",
doi = "10.1126/sciadv.aax6328",
language = "English",
volume = "6",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "11",
}