Constraint of Lignin-Carbohydrate Complex Orchestrated on Polyphenol in Oil-Water Interface Targeting Ulcerative...

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 W₁/O/W₂ 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 W₁/O/W₂ 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.