Production of Hydroxycarboxylic Acid Receptor 3 (HCA₃) Ligands by Bifidobacterium

Hydroxycarboxylic acid receptor 3 (HCA₃) was recently identified in the genomes of humans and other hominids but not in other mammals. We examined the production of HCA₃ 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 HCA₃ ligand. The four ligands produced were the mixtures of enantiomers, and D-ILA, D-PLA, and D-LeuA showed stronger activity of the HCA₃ 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 HCA₃ ligands produced by Bifidobacterium and suggest the importance of investigating the absolute stereo structures of these metabolites.