Oral hydrogel systems in lower gastrointestinal disorders: From disease-based therapy to microbiota-guided design.

The lower gastrointestinal tract is a complex ecological system involved in epithelial barrier maintenance, immune regulation, microbial metabolism, and host homeostasis. Disruption of this environment is closely associated with lower gastrointestinal disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colorectal cancer (CRC). Conventional therapies often face limitations such as poor drug stability, low solubility, insufficient intestinal retention, limited targeting efficiency, and systemic adverse effects. Oral hydrogel systems have emerged as promising platforms for lower gastrointestinal therapy because of their biocompatibility, tunable physicochemical properties, controlled-release behavior, and responsiveness to intestinal microenvironmental cues. However, most existing studies have been developed primarily from a disease-based therapeutic perspective, focusing on inflammation suppression, oxidative stress regulation, epithelial barrier repair, tumor inhibition, or symptom relief, while gut microbiota alterations are often evaluated as accompanying outcomes. In this review, we discuss oral hydrogel systems for lower gastrointestinal disorders from the perspective of the transition from disease-based therapy to microbiota-guided design. We summarize the physiological barriers and design basis of oral hydrogel systems, disease-oriented applications in IBD, CRC, gut-brain axis-related disorders, and microbiota-associated metabolic disorders, and emerging microbiota-oriented hydrogel strategies. We further discuss hydrogel-microbiota-host interactions, microbiota-related design principles, and translational challenges. This review aims to clarify how oral hydrogel systems can evolve from conventional drug delivery platforms toward microbiota-guided therapeutic systems for lower gastrointestinal disorders.