Journal article
Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut
Research Group for Gut, Microbes and Health, National Food Institute, Technical University of Denmark1
Research Group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark2
National Food Institute, Technical University of Denmark3
Mucosal Immunology, Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark4
Department of Health Technology, Technical University of Denmark5
Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark6
Disease Systems Immunology, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark7
Department of Biotechnology and Biomedicine, Technical University of Denmark8
University of Copenhagen9
Kyoto University10
...and 0 moreBreastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known.
Here, we demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH).
The ability of Bifidobacterium species to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degrading Bifidobacterium species containing the ALDH, including Bifidobacterium longum, B. breve and B. bifidum.
We further demonstrate that faecal concentrations of Bifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+ T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3).
Our findings reveal that breastmilk-promoted Bifidobacterium species produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2021 |
Pages: | 1367-1382 |
ISSN: | 20585276 |
Types: | Journal article |
DOI: | 10.1038/s41564-021-00970-4 |
ORCIDs: | 0000-0002-6367-1309 , 0000-0003-0449-0839 , 0000-0002-5311-9457 , 0000-0002-4999-1218 , 0000-0003-0609-6317 , Roager, Henrik M. , Laursen, Martin F. , von Burg, Nicole , Mörbe, Urs , Andersen, Daniel , Moll, Janne Marie , Rivollier, Aymeric , Frandsen, Henrik L. , Vinggaard, Anne Marie , Bahl, Martin I. , Brix, Susanne , Agace, William , Licht, Tine R. and 0000-0003-4009-7874 |