Surface Assembling of Individual Probiotics with pH-Responsive Epigallocatechin Gallate Nanoparticles against DSS-induced colitis

Probiotics are potential treatments for inflammatory bowel diseases, but their efficacy is primarily restricted by the adverse gastrointestinal conditions that limit activity and adhesion. In light of the high bioactivity and the strong absorption onto mucus layer and bacterial surface of polyphenols, it’s of considerable interest in developing a polyphenol-based collaborative platform to coat probiotics for improved efficacy. Here, we developed a single-cell coating strategy with polyphenol nanoparticles self-assembling on cellular surface through Mannich reaction-induced self-assembly of polyphenols. Polyphenols adhering on bacterial cells underwent a Mannich condensation reaction to produce oligomeric derivatives, which assembled to generate nanoparticles through intermolecular entanglement and interaction via primarily hydrophobic π − π stacking and intermolecular hydrogen bonds. Probiotics were coated individually with the self-assembled nanoparticles in 30 min. The pH-responsive nanoparticles kept stable at low pH (2–6) and disassembled at high pH (7–9), resulting in improved probiotic viability against acidic gastric fluid and bile salts, and enhanced colonization in the intestinal tract without loss of proliferation capabilities. Furthermore, the polyphenols can also trigger significant antioxidant, anti-inflammatory, and barrier-protective effects, thereby synergizing with probiotics to alleviate colitis in mice. This surface self-assembling strategy represents a robust platform to enhance the potency of probiotics for the treatment of ulcerative colitis.