Constraint of Lignin–Carbohydrate Complex Orchestrated on Polyphenol in Oil–Water Interface Targeting Ulcerative Colitis Therapy

ABSTRACT The therapeutic potential of polyphenols in ulcerative colitis (UC), mediated through immune modulation and gut microbiota homeostasis. To enhance the oral bioavailability of polyphenols, we architected a colon–targeted W ₁ /O/W ₂ emulsion system featuring a rationally designed lignin–carbohydrate complex (LCC) as a dual–functional emulsifier system for the first time. Based on the innate structural duality of LCC, which comprising hydrophobic lignin and hydrophilic carbohydrates, we employed LCC for O/W emulsifier. This inherent amphiphilicity was further engineered via laccase–mediated grafting of isovanillin, yielding a modified LCC with tailored lipophilicity for effective W/O interfacial stabilization. The W ₁ /O/W ₂ emulsion ensured the stability of the encapsulated polyphenols with divergent polarity but also enabled pH–responsive payload release under colonic conditions (pH >7.0). In DSS–induced colitis, the system demonstrated a synergistic effect, the LCC itself acted as a prebiotic to modulate the gut microbiota, specifically enriching short chain fatty acid–producing bacteria, while the released polyphenols reinforced the intestinal barrier, which collectively accelerated mucosal healing. This research proposes a carbon–neutral therapeutic strategy for colitis, not only establishing a proof–of–concept for replacing synthetic emulsifiers with engineered biomass, but also as a multi–functional platform to stabilize colon–targeted co–delivery system and microbiome regulation in colitis.