Journal
SCIENCE ADVANCES
Volume 6, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax6328
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Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)-CASE studentship - AstraZeneca
- BBSRC [BB/K008005/1, BB/P003281/1]
- Wellcome Trust/Royal Society Sir Henry Dale fellowship [104116/Z/14/Z]
- Cancer Research UK [C596/A17196, 23982]
- Multiple Sclerosis Society UK [38]
- Wellcome Trust [097820/Z/11/B]
- Wellcome Trust [104116/Z/14/Z] Funding Source: Wellcome Trust
- BBSRC [BB/K008005/1, BB/L000121/1] Funding Source: UKRI
- MRC [MC_PC_12020] Funding Source: UKRI
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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.
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