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 language | English |
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Article number | eaax6328 |
Number of pages | 11 |
Journal | Science Advances |
Volume | 6 |
Issue number | 11 |
DOIs | |
Publication status | Published - 11 Mar 2020 |
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).
Keywords
- gut microbiome
- carnitine
- microbial metabolites
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Ruangelie Edrada-Ebel
- Strathclyde Institute Of Pharmacy And Biomedical Sciences - Senior Lecturer
Person: Academic