Advances in Protein‐Based Delivery Systems: From Structural Design to Smart Responses and Intestinal Microbiome Modulation

While bioactive compounds hold significant potential for health promotion, their application is severely constrained by issues such as poor stability, low oral bioavailability, and susceptibility to degradation in the gastrointestinal environment. Protein-based delivery systems (PBDS), as novel carriers, demonstrate the potential to overcome these challenges through encapsulation and targeted release technologies. This paper provides a systematic review of the latest research advances in various PBDS systems, including Pickering emulsions, protein-small molecule complexes, protein-polysaccharide complexes, nanogels, nanoparticles, core-shell microcapsules, self-assembled nanotubes, and nanofibers, along with their performance and characteristics in encapsulation, protection, and controlled release. PBDS enables smart stimulus-responsive release through pH, temperature, enzymatic reactions, redox reactions, and receptor recognition, thereby enhancing targeted delivery and controlled release efficiency. Furthermore, PBDS interacts with the gut microbiota to modulate microbial composition and strengthen intestinal barrier function, positively impacting systemic metabolic health. In summary, PBDS offers a solution for developing next-generation functional foods with improved nutritional properties, sensory qualities, and storage performance. Future research should focus on novel protein sources, multi-stimulus response design, scalable preparation processes, and in-depth exploration of PBDS-microbiome interaction mechanisms to advance personalized nutrition and smart food applications.