Production of Hydroxycarboxylic Acid Receptor 3 (HCA(3)) Ligands by Bifidobacterium

Hydroxycarboxylic acid receptor 3 (HCA(3)) was recently identified in the genomes of humans and other hominids but not in other mammals. We examined the production of HCA(3) ligands by Bifidobacterium spp. In addition to 4-hydroxyphenyllactic acid, phenyllactic acid (PLA), and indole-3-lactic acid (ILA), we found that LeuA was produced by Bifidobacterium as an HCA(3) ligand. The four ligands produced were the mixtures of enantiomers, and D-ILA, D-PLA, and D-LeuA showed stronger activity of the HCA(3) ligand than their respective L-isomers. However, there was no difference in AhR activity between the two ILA enantiomers. These results provide new insights into the HCA(3) ligands produced by Bifidobacterium and suggest the importance of investigating the absolute stereo structures of these metabolites.