TY - JOUR
T1 - Biodistribution and racemization of gut-absorbed l/d-alanine in germ-free mice
AU - Qiu, Tian (Autumn)
AU - Lee, Cindy J.
AU - Huang, Chen
AU - Lee, Dong Kyu
AU - Rubakhin, Stanislav S.
AU - Romanova, Elena V.
AU - Sweedler, Jonathan V.
N1 - Funding Information:
The authors thank Dr. Fuming Pan and J. Reid McClure at the UIUC Rodent Gnotobiotic Facility for their assistance in germ-free animal experiments. We thank Nissa J. Larson for her help in the BCA experiments and Dr. Peter Chan-Andersen for their help in mass spectrometry experiments on peptide profiling. We thank Theren Williams at the Illinois Statistics Office for his help in statistics. This work was supported by a Beckman Institute Postdoctoral Fellowship at UIUC from the Arnold and Mabel Beckman Foundation and a Mistletoe Research Fellowship from the Momental Foundation (T.A.Q.), by the Pilot Project Grant Program from Office of the Vice Chancellor for Research at University of Illinois, by Award No. R01NS031609 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (J.V.S.), and by support from the American Diabetes Association Pathway to Stop Diabetes Grant No. 1-18-VSN-19 (J.V.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Funding Information:
The authors thank Dr. Fuming Pan and J. Reid McClure at the UIUC Rodent Gnotobiotic Facility for their assistance in germ-free animal experiments. We thank Nissa J. Larson for her help in the BCA experiments and Dr. Peter Chan-Andersen for their help in mass spectrometry experiments on peptide profiling. We thank Theren Williams at the Illinois Statistics Office for his help in statistics. This work was supported by a Beckman Institute Postdoctoral Fellowship at UIUC from the Arnold and Mabel Beckman Foundation and a Mistletoe Research Fellowship from the Momental Foundation (T.A.Q.), by the Pilot Project Grant Program from Office of the Vice Chancellor for Research at University of Illinois, by Award No. R01NS031609 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (J.V.S.), and by support from the American Diabetes Association Pathway to Stop Diabetes Grant No. 1-18-VSN-19 (J.V.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85168240003&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85168240003&partnerID=8YFLogxK
U2 - 10.1038/s42003-023-05209-y
DO - 10.1038/s42003-023-05209-y
M3 - Article
C2 - 37587187
AN - SCOPUS:85168240003
SN - 2399-3642
VL - 6
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 851
ER -