Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication.
Sci Adv
; 6(11): eaax6328, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-32195337
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_zoonosis
Asunto principal:
Carnitina
/
Sustancia Blanca
/
Clostridiales
/
Microbioma Gastrointestinal
/
Mucosa Intestinal
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido