Reprogramming the gastrointestinal microenvironment with intelligent biomaterials and digital medicine: a perspective...

Digestive diseases, including inflammatory bowel disease (IBD), gastrointestinal mucosal injury, colorectal cancer-associated inflammation, peptic ulcer disease, and postoperative gastrointestinal complications, are increasingly understood as disorders of a dynamic and spatially heterogeneous microenvironment rather than isolated abnormalities of a single tissue, cell type, or molecular pathway. The gastrointestinal microenvironment integrates epithelial barrier integrity, immune activation, microbiota composition, metabolic gradients, vascular remodeling, neural regulation, luminal pH, enzymatic activity, and mechanical stress. However, current clinical management remains largely organized around episodic diagnosis, systemic pharmacotherapy, endoscopic assessment, and reactive treatment escalation. This paradigm is insufficient for diseases characterized by relapsing inflammation, barrier disruption, microbiome instability, and patient-specific trajectories. Recent advances in intelligent biomaterials, artificial intelligence, digital health, and digital twin modeling create an opportunity to rethink gastrointestinal disease intervention as a process of microenvironmental reprogramming. In this Perspective, we propose that the next-generation of digestive disease care should move from disease suppression toward programmable regulation of the gastrointestinal microenvironment. Intelligent biomaterials are being investigated as locally acting therapeutic interfaces capable of responding to pH, enzymes, reactive oxygen species (ROS), inflammatory mediators, microbiota-derived metabolites, or tissue injury signals. Meanwhile, artificial intelligence (AI) and digital medicine are being developed to integrate endoscopic imaging, histology, multi-omics, symptoms, wearable data, microbiome profiles, and treatment history to support patient-specific decision-making. We argue that the key translational challenge is not simply to develop more advanced materials or more accurate algorithms in isolation, but to integrate digital interpretation with locally acting biomaterial interventions in clinically executable therapeutic systems. Using inflammatory bowel disease and related gastrointestinal disorders as representative contexts, this Perspective outlines current advances, conceptual gaps, and future directions for combining intelligent biomaterials and digital medicine to enable precision intervention in digestive diseases.