Gut‐Targeted Nutraceutical Delivery: Engineering Microbiome‐Responsive Nutraceutical Interfaces

ABSTRACT The gut microbiome plays a central role in maintaining host health, influencing immunity, metabolism, epithelial integrity, and the gut–brain axis. Dysbiosis of this complex microbial ecosystem is implicated in a variety of chronic diseases, including inflammatory bowel disease, metabolic syndrome, and neurological disorders. Nutraceuticals such as prebiotics, polyphenols, probiotics, postbiotics, bioactive peptides, and micronutrients—hold promise for restoring microbial homeostasis and supporting gut health. However, their clinical utility is limited by poor stability, premature degradation in the upper gastrointestinal tract, and variability in microbiome composition. Recent advances in microbiome‐responsive delivery systems have addressed these challenges by engineering smart platforms that synchronize bioactive release with the unique biochemical signals of the gut, including pH gradients, microbial enzymes, redox cues, and fermentation‐driven changes. These innovative systems, incorporating pH‐sensitive hydrogels, enzyme‐ and redox‐responsive nanogels, hybrid polymer carriers, synbiotic co‐encapsulation, functional food matrices, and edible coatings, enhance nutraceutical stability, bioavailability, and site‐specific action. Preclinical and emerging clinical evidence demonstrates their potential to modulate the microbiome, attenuate inflammation, and promote mucosal healing. Despite encouraging progress, translational hurdles—such as limited human trials, regulatory uncertainties, and interindividual variability—must still be overcome. This review comprehensively explores the design principles, mechanisms, applications, and future perspectives of microbiome‐responsive nutraceutical interfaces, highlighting their transformative potential in advancing personalized gut health interventions.