An Adaptive In Situ Biointerfacial Armoring Platform for Long-Term Gut Microbiota Modulation

Abstract

Despite the immense potential against diverse chronic inflammatory and metabolic disorders, the clinical translation of microbial therapies is largely thwarted by the delivery challenges of live biotherapeutics. Probiotics often succumb to harsh gastrointestinal conditions and oxidative stress. We report ARMOG, a microenvironment responsive platform achieving in situ biointerfacial transformation. Composed of hyaluronic acid with an increased dopamine grafting ratio cross-linked by arylboronic acid, the matrix undergoes cleavage triggered by the inflammatory microenvironment, leading to localized dopamine polymerization directly onto bacterial surfaces. This “armoring” mechanism creates a resilient interface that enhances survival and mucosal anchoring. This stable scaffold operates without species-specific constraints, optimizing both single-strain delivery and fecal microbiota transplantation (FMT). Demonstrated in representative models of acute/chronic colitis and cancer, ARMOG effectively remodels the gut microbiota and promoting commensals while suppressing pro-inflammatory cell infiltration. By transforming microbial colonization into sustainable ecological restoration using biocompatible materials, ARMOG offers a generalizable strategy for restoring host-microbe homeostasis and intercepting the progression toward severe pathologies.