Abstract
AbstractMicrobiome-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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
American Diabetes Association
Arnold and Mabel Beckman Foundation
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)