Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut
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Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut. / Laursen, Martin Frederik; Sakanaka, Mikiyasu; von Burg, Nicole; Mörbe, Urs; Andersen, Daniel; Moll, Janne Marie; Pekmez, Ceyda Tugba; Rivollier, Aymeric; Michaelsen, Kim F.; Mølgaard, Christian; Lind, Mads Vendelbo; Dragsted, Lars Ove; Katayama, Takane; Frandsen, Henrik Lauritz; Vinggaard, Anne Marie; Bahl, Martin Iain; Brix, Susanne; Agace, William; Licht, Tine R; Roager, Henrik Munch.
I: Nature Microbiology, Bind 6, Nr. 11, 2021, s. 1367-1382.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut
AU - Laursen, Martin Frederik
AU - Sakanaka, Mikiyasu
AU - von Burg, Nicole
AU - Mörbe, Urs
AU - Andersen, Daniel
AU - Moll, Janne Marie
AU - Pekmez, Ceyda Tugba
AU - Rivollier, Aymeric
AU - Michaelsen, Kim F.
AU - Mølgaard, Christian
AU - Lind, Mads Vendelbo
AU - Dragsted, Lars Ove
AU - Katayama, Takane
AU - Frandsen, Henrik Lauritz
AU - Vinggaard, Anne Marie
AU - Bahl, Martin Iain
AU - Brix, Susanne
AU - Agace, William
AU - Licht, Tine R
AU - Roager, Henrik Munch
N1 - © 2021. The Author(s).
PY - 2021
Y1 - 2021
N2 - Breastfeeding 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.
AB - Breastfeeding 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.
U2 - 10.1038/s41564-021-00970-4
DO - 10.1038/s41564-021-00970-4
M3 - Journal article
C2 - 34675385
VL - 6
SP - 1367
EP - 1382
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
IS - 11
ER -
ID: 282475449