Hydrogel-based Probiotic Delivery Systems for Gut Microbiota and Homeostasis Regulation from Bench to Bedside

Abstract The modulation of gut microbiota is critical for intestinal homeostasis and addressing disorders such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics have gained attention for maintaining gut health, but ensuring their survival until reaching the target intestinal area remains a significant challenge. Hydrogels, owing to their biocompatibility, tunable release profiles, protective capabilities, and ease of modification, serve as promising platforms for delivering probiotics, bioactive compounds, and chemotherapeutics. This review provides an overview of advancements in hydrogel-based probiotic delivery systems as innovative tools for influencing gut microbiota composition and function. We examine the latest hydrogel formulations designed to enhance probiotic viability and ensure localized release, which are essential for restoring microbial balance. Additionally, we explore the mechanisms underlying probiotic loading and release, and their effects on immune responses, microbial diversity, and metabolic homeostasis. This review highlights significant preclinical evidence demonstrating the therapeutic efficacy of these systems in models of IBD and CRC, underscoring their potential to improve clinical outcomes. Ultimately, we aim to guide future research and facilitate the clinical application of hydrogel-based strategies for regulating gut microbiota and promoting intestinal health.