Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication

Heather Hulme, Lynsey M Meikle, Nicole Strittmatter, Justin J J van der Hooft, John Swales, Ryan A Bragg, Victor H Villar, Michael J Ormsby, Stephanie Barnes, Sheila L Brown, Alex Dexter, Maya T Kamat, Jasper C Komen, Daniel Walker, Simon Milling, Emily K. Osterweil, Andrew S MacDonald, Chris J Schofield, Saverio Tardito, Josephine BunchGillian Douce, Julia M Edgar, RuAngelie Edrada-Ebel, Richard J A Goodwin, Richard Burchmore, Daniel M Wall

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article numbereaax6328
Pages (from-to)1-10
Number of pages10
JournalScience Advances
Volume6
Issue number11
DOIs
Publication statusPublished - 11 Mar 2020

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