Saffron Alters Microbial Amino Acid Metabolism and Neurotransmitter Production in a Defined Gut Consortium

The gut microbiota relies on both dietary and host-derived substrates to shape community composition, metabolic activity, and host physiology. While dietary fibers have been extensively studied as microbial substrates, less is known about how bioactive plant compounds influence microbial metabolism. The spice saffron, the stigma from the Crocus sativus flower, is commonly used for its medicinal traits, yet its effects on gut microbial communities remain poorly understood. Here, we used a defined human commensal consortium grown in anaerobic bioreactors to investigate how saffron alters bacterial metabolism. Saffron treatment significantly remodeled amino acid utilization and metabolite output, reducing tryptophan while increasing its downstream products tryptamine and indole acetic acid. In parallel, saffron elevated the levels of neuroactive compounds including GABA, glutamate, glycine, and dopamine, while decreasing L-DOPA, tyrosine, and anthranilic acid. Short-chain fatty acid (SCFA) profiles were also shifted, with increased formic and isobutyric acids, decreased propionic, butyric, and valeric acids, and no change in acetate, 2-methyl-butyric acid, and isovaleric acid. Together, these findings demonstrate that saffron profoundly reprograms microbial amino acid and neurotransmitter metabolism while reshaping SCFA production. This work provides new insight into how dietary bioactive compounds modulate microbial metabolic networks, with potential implications for gut and brain health.