Work

Biodistribution and racemization of gut-absorbed l/d-alanine in germ-free mice

Year: 2023

Type: article

Abstract: 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.

Source: Communications Biology

DOI: 10.1038/s42003-023-05209-y