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Citation

Hulme H, Meikle LM, Strittmatter N, van der Hooft JJJ, Swales J, Bragg RA, Villar VH, Ormsby MJ, Barnes S, Brown SL, Dexter A, Kamat MT, Komen JC, Walker D & Milling S (2020) Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication. Science Advances, 6 (11), Art. No.: eaax6328. https://doi.org/10.1126/SCIADV.AAX6328

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.

Notes
Additional co-authors: Emily K. Osterweil, Andrew S. MacDonald, Chris J. Schofield, Saverio Tardito, Josephine Bunch, Gillian Douce, Julia M. Edgar, RuAngelie Edrada-Ebel, Richard J. A. Goodwin, Richard Burchmore, Daniel M. Wall

Journal
Science Advances: Volume 6, Issue 11

• Published version