Breastmilk-promoted bifidobacteria produce aromatic lactic acids in the infant gut

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development. However, few breastmilk-dependent microbial metabolites mediating host-microbiota interactions are currently known. We here demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactate, phenyllactate and 4-hydroxyphenyllactate) via a previously unrecognised aromatic lactate dehydrogenase. By longitudinal profiling of the gut microbiota composition and metabolome of stool samples of infants obtained from birth until 6 months of age, we show that stool concentrations of aromatic lactic acids is determined by the abundance of human milk oligosaccharide degrading Bifidobacterium species containing the aromatic lactate dehydrogenase. Finally, we demonstrate that stool concentrations of Bifidobacterium-derived indolelactate are associated with the capacity of infant stool samples to activate the aryl hydrocarbon receptor, a receptor important for maintenance of intestinal homeostasis and immune system development. These findings open up new directions towards understanding the role of breastmilk-promoted Bifidobacterium in mediating host-microbiota interactions in early life.