Targeted Extraction of Gut-Brain Axis Bioactives: A Review

The gut-brain axis (GBA) represents a bidirectional communication network linking the gastrointestinal tract and central nervous system (CNS), with gut microbiota-derived metabolites playing critical roles in modulating neurotransmission, barrier function, and neuroinflammation. Dietary bioactive compounds such as polyphenols, tryptophan, only 1% of dietary tryptophan is converted to serotonin, with the remaining 95% metabolized via the kynurenine pathway fermentable fibers, and bitter tastants modulate GBA mechanisms through the tryptophan-serotonin-kynurenine pathway, short-chain fatty acid (SCFA)-FFAR signaling, vagal-enteric nervous system activation, microbial metabolite production, and anti-inflammatory barrier function pathways. However, conventional extraction methods employ prolonged times, high temperatures, and toxic solvents that degrade these heat-labile bioactives and prioritize chemical yield over bioactivity preservation, compromising functional efficacy for GBA targets. A critical gap remains because no existing framework integrates targeted extraction strategies with the specific mechanistic requirements of the gut-brain axis. This review provides a rational framework for developing next-generation functional foods targeting the gut-brain axis, emphasizing the need for integrated, mechanism-driven extraction, rigorous validation, and harmonized safety assessment to enable clinical translation.