Refining the gut-microbiome axis: A triad of metabolites, targeted microbial delivery, and AI-assisted profiling for precision medicine-food intervention

The gut microbiota is widely recognized as a central regulator of human health and disease. Medicine-food homologous resources, leveraging their inherent safety and multi-target characteristics, serve as pivotal modulators for intervening in metabolic, inflammatory, and immune-related disorders via microbiota regulation. However, the inherent complexity, substantial interindividual variability, and dynamic nature of the gut microbiome remain major hurdles to achieving precise interventions. This perspective delineates a novel paradigm for precision medicine-food intervention, built upon three interconnected and cutting-edge directions: (1) targeting key microbial metabolites, (2) advancing targeted delivery technologies for beneficial microbes, and (3) implementing artificial intelligence (AI)-assisted personalized microbiome functional profiling. This triad synergistically addresses the challenge of individual variability and paves the way for highly effective and precise interventions.

1. Key Microbial Metabolites: The Core Targets and Effector Hubs of Medicine-Food Intervention

Gut microbial metabolites act as central mediators through which the microbiota influences host physiology, directly targeting critical processes such as intestinal barrier integrity, immune modulation, and metabolic homeostasis. They represent both direct targets and ultimate effector molecules of medicine-food interventions. The network formed by these metabolites serves as the biochemical bridge connecting the “microbiota, host, and medicine-food components.” The paramount value of bioactive compounds from medicine-food homologous resources lies in their ability to selectively shape the structure and function of specific functional microbial communities, thereby modulating the profile and abundance of beneficial metabolite networks and ultimately mediating positive health outcomes. Consequently, an in-depth understanding and precise targeting of key metabolite networks constitute the biochemical foundation for achieving precision in medicine-food interventions. The state and dynamics of this metabolite network also serve as crucial inputs for AI profiling and core metrics for evaluating intervention efficacy.

2. Targeted Delivery of Beneficial Microbes: Overcoming Barriers to Empower Precision Intervention

Conventional medicine-food intervention approaches (e.g., direct supplementation of probiotics or prebiotics) often suffer from challenges like low colonization efficiency, poor survival rates, and high interindividual response heterogeneity, which limit the stability and potency of outcomes. The breakthrough development of targeted delivery technologies for beneficial microbes provides essential tools to overcome these bottlenecks and enhance the precision and efficiency of interventions. Advanced delivery systems (e.g., microencapsulation, nanocarriers, biomaterial encapsulation) aim to protect functional microbial strains from degradation in harsh gastrointestinal environments (e.g., gastric acid, bile), achieve controlled release of active agents, and enable precise delivery to specific target regions of the gut (e.g., colon), thereby significantly improving the survival, colonization, and functional activity of target strains. Crucially, “prebiotic + probiotic” co-delivery strategies, by providing selective growth substrates for specific functional strains, can synergistically enhance the colonization competitiveness and functional expression of the target microbes. The effective implementation of these delivery strategies relies heavily on personalized insights (e.g., target microbes, target delivery site) provided by AI profiling, and their success is directly measured by the effective production and functional manifestation of the target beneficial metabolites.

3. AI-Powered Personalized Microbiome Functional Profiling: The Core Engine for Precision Intervention

The profound interindividual variability in gut microbiome structure and function poses the greatest challenge to achieving “one-size-fits-one” precision medicine-food interventions. Traditional methods struggle to capture this complexity and deliver effective personalized solutions. Artificial intelligence (AI)-assisted personalized microbiome functional profiling emerges as the core engine to overcome this challenge. Here, “profiling” refers to the use of AI and machine learning (ML) technologies to deeply integrate multi-omics data (metagenomics, metabolomics, transcriptomics, etc.) for the comprehensive assessment and prediction of an individual's gut microbiome's functional status, metabolic potential, responsiveness to specific intervention components, and potential for disease improvement, effectively creating a personalized “gut health blueprint.” AI models trained on large-scale datasets can predict an individual's response type to specific medicine-food formulations, simulate microbiome dynamics under intervention, and estimate potential health benefits. Crucially, the core output of AI profiling lies in its ability to directly guide precision intervention practices: designing individualized prebiotic combinations, tailoring targeted probiotic formulations, optimizing delivery system parameters (e.g., release site, release kinetics), and planning personalized intervention schedules (components, dosage, timing), thereby achieving a three-dimensional precision match of “individual-microbiome-medicine-food strategy.” This approach holds immense potential for the personalized management of complex chronic diseases like metabolic disorders and chronic inflammation. AI profiling requires the integration of metabolite data as a critical input, and the personalized plans it generates ultimately serve the purpose of precisely regulating the metabolite network through targeted delivery.

In conclusion，the role of the gut microbiota in medicine-food interventions is undergoing a profound shift, evolving into an actively engineered core target. The novel “Targeted Metabolites - Empowered Delivery - AI Navigation” triad paradigm proposed herein represents the future mainstream direction for precision medicine-food intervention. This paradigm leverages AI-driven personalized profiling to provide a precise navigation map, guiding targeted delivery technologies to efficiently and accurately transport beneficial agents to their intended destinations, ultimately achieving the directional remodeling of key beneficial metabolite networks and forming a dynamically optimized closed loop. This integrated strategy fundamentally addresses the pain points of traditional interventions—high interindividual variability and inconsistent efficacy—propelling medicine-food homology from population-based generality toward genuine individual precision. Looking ahead, key research frontiers include in-depth deciphering of core metabolite networks, developing intelligent responsive delivery systems, constructing high-fidelity dynamic multi-omics integrated AI models, and developing personalized products based on this paradigm. This emerging paradigm will not only significantly enhance the precision prevention and management capabilities for chronic diseases such as metabolic syndrome, obesity, non-alcoholic fatty liver disease, and inflammatory bowel disease but will also profoundly drive innovation in the modernization of traditional medicine, the precision of functional foods, and the precision nutrition industry. It paves a new path for understanding the complex “microbiota-host-diet” interaction network and revolutionizing disease prevention and management models.

About the Author

Zhang Qian is an Associate Researcher and a correspondence review expert for the National Natural Science Foundation of China (NSFC). He serves on the Young Editorial Boards of iMeta, Food & Medicine Homology, Journal of Future Foods, Traditional Medicine Research, Integrative Medicine Discovery, Pharmaceutical Science Advances, Infectious Diseases Research, Biomedical Engineering Communications, Medicine Advances, the Journal of Southern Medical University, and Shandong Science, and is an Executive Director of the Inner Mongolia Pharmacological Society. His research focuses on: (1) the anti-inflammatory and immunopharmacology of traditional Chinese medicine (TCM) and medicine–food homology resources; (2) mechanisms by which probiotics influence human health; and (3) disease modulation by TCM/probiotics via regulation of the gut microbiota, bioactive lipids, and lipid-mediated signaling pathways. He is currently PI on one NSFC project, one Ministry of Education Industry–University–Research Collaborative Education Project, five provincial projects, and five university-level projects, and has participated in five additional NSFC projects. He has published 30+ papers in SCI-indexed and Chinese journals. Honors include the 2024 Outstanding Young Editorial Board Member and Outstanding Reviewer awards from Traditional Medicine Research, the 2025 Q1 Academic Communication Contribution Award from Food & Medicine Homology, and the 2023 Inner Mongolia Medical University Innovation Talent Award.