Gut microbiota-targeted bioactive peptides as emerging axis in nutritional therapeutics: trends, challenges, and prospects.

The gut microbiota is a dynamic, complex microbial ecosystem that is fundamental to human health and influences metabolism, immunity, and susceptibility to disease. There is growing evidence that bioactive peptides (BAPs) are important regulators of gut microbiota composition and function. BAPs are short protein fragments liberated through enzymatic hydrolysis or microbial fermentation in vitro and during the digestion of food proteins in vivo. The biological activities of these BAPs, beyond their antioxidant, antihypertensive, and antimicrobial effects, include maintaining gut balance and supporting overall well-being. The relationship between BAPs and gut microbiota is two-way: peptides selectively promote beneficial microbes, and the microbiota enzymatically convert peptides into bioactive metabolites such as short-chain fatty acids and altered bile acids, or further hydrolyze them into shorter BAPs. This interaction between gut microbiota and BAPs has been shown to confer significant therapeutic benefits from combined nutritional interventions in the management of chronic diseases, including obesity, diabetes, inflammatory bowel diseases, and neurological diseases. This review examines the current state of gut microbiota-targeted BAPs, including their sources, properties, and mechanisms. It underscores their contribution to microbial diversity and metabolic activity, which support immune balance and the functioning of the gut-brain axis. In addition, it addresses novel ways to increase the activity of BAPs with respect to stability and delivery. Challenges such as peptide bioavailability, microbiome diversity, and a lack of clinical evidence are also critically discussed. Future perspectives focus on leveraging omics technologies and personalized nutrition to unlock the potential of BAPs for therapeutic and functional food applications. The review indicates the promising potential of BAPs as microbiota-based, innovative, and useful agents in nutritional therapy.