Biodistribution and racemization of gut-absorbed L/D-alanine in germ-free mice.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
16 08 2023
Historique:
received: 02 01 2023
accepted: 03 08 2023
medline: 18 8 2023
pubmed: 17 8 2023
entrez: 16 8 2023
Statut: epublish

Résumé

Microbiome-derived metabolites are important for the microbiome-gut-brain axis and the discovery of new disease treatments. D-Alanine (D-Ala) is found in many animals as a potential co-agonist of the N-methyl-D-aspartate receptors (NMDAR), receptors widely used in the nervous and endocrine systems. The gut microbiome, diet and putative endogenous synthesis are the potential sources of D-Ala in animals, although there is no direct evidence to show the distribution and racemization of gut-absorbed L-/D-Ala with regards to host-microbe interactions in mammals. In this work, we utilized germ-free mice to control the interference from microbiota and isotopically labeled L-/D-Ala to track their biodistribution and racemization in vivo. Results showed time-dependent biodistribution of gut-absorbed D-Ala, particularly accumulation of gut-absorbed D-Ala in pancreatic tissues, brain, and pituitary. No endogenous synthesis of D-Ala via racemization was observed in germ-free mice. The sources of D-Ala in mice were revealed as microbiota and diet, but not endogenous racemization. This work indicates the importance of further investigating the in vivo biological functions of gut-microbiome derived D-Ala, particularly on NMDAR-related activities, for D-Ala as a potential signaling molecules in the microbiome-gut-brain axis.

Identifiants

pubmed: 37587187
doi: 10.1038/s42003-023-05209-y
pii: 10.1038/s42003-023-05209-y
pmc: PMC10432453
doi:

Substances chimiques

Alanine OF5P57N2ZX
Receptors, N-Methyl-D-Aspartate 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

851

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Tian Autumn Qiu (TA)

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Department of Chemistry, Michigan State University, East Lansing, MI, USA.

Cindy J Lee (CJ)

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.

Chen Huang (C)

Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.

Dong-Kyu Lee (DK)

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.
College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.

Stanislav S Rubakhin (SS)

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.

Elena V Romanova (EV)

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.

Jonathan V Sweedler (JV)

Department of Chemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA. jsweedle@illinois.edu.
Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, USA. jsweedle@illinois.edu.
Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA. jsweedle@illinois.edu.

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Classifications MeSH