Microbiota-derived aromatic amino acid decarboxylases: linking microbial fitness and host neurochemical communication

The human microbiota produces a diverse array of bioactive molecules, including classic neurotransmitters (dopamine and serotonin) and trace amines (tryptamine, tyramine, and phenylethylamine). Although long considered products of host metabolism, these aromatic monoamines are now also known to originate in part from the microbiota, where they are synthesized by bacterial aromatic L-amino acid decarboxylases (AADCs). This review explores the distribution, biochemical diversity, and host interactions of microbiota-encoded AADCs, highlighting their roles in gut and skin ecosystems. Bacterial AADCs vary in gene organization, substrate range, and expression patterns across taxa like Ruminococcus gnavus, Clostridium sporogenes, Enterococcus spp., and Staphylococcus spp. These enzymes contribute to microbial fitness through acid stress resistance, energy generation via proton motive force, epithelial adherence and internalization, and niche dominance. Critically, their products modulate host physiology via trace amine-associated receptors (TAARs) and other signaling pathways, influencing neurotransmission, immune response, barrier integrity, and metabolism. Microbiota-derived monoamines can enter systemic circulation and cross the blood-brain barrier, implicating them in disorders ranging from irritable bowel syndrome to neurodegeneration. Emerging data also reveal their impact on wound healing and drug efficacy, notably in Parkinson's disease. By positioning microbial AADCs as key players in host-microbe chemical communication, this review underscores their relevance for health and disease and highlights them as potential therapeutic targets.