Spore germinator-loaded polysaccharide microspheres ameliorate colonic inflammation and tumorigenesis through remodeling gut microenvironment

The abnormal intestinal features like increased epithelial oxygenation, elevated inflammatory cascades and excess nitrate production can exacerbate colitis progression and even trigger colorectal cancer by promoting gut microbiota dysbiosis. Here, probiotic spores decorated with anti-inflammatory curcumin are encapsulated into cysteine-modified konjac glucomannan microspheres, to intervene colitis and colonic cancerization through remodeling gut microenvironment. Benefiting from the prolonged intestinal retention effect of polysaccharide microspheres, epithelial oxygenation is effectively restored into hypoxia in colon location due to spore germination-induced oxygen consumption, which blunts luminal Enterobacteriaceae overgrowth, and facilitates short chain fatty acids (SCFAs)-producing bacteria. By fermenting prebiotics of konjac glucomannan, the produced butyrate by SCFAs-producing bacteria further converts cell energy metabolism from glycolysis to oxygen-consumed β-oxidation by activating epithelial peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling, resulting in thorough oxygen outage, nitrate production-related enzymes downregulation and inflammatory response elimination. In view of directed gut microbiota modulation and colonic epithelial cell functions normalization, the potent intervention effect of spore germinator-loaded polysaccharide microspheres is achieved in multiple colitis models and genotoxic colibactin-producing Enterobacteriaceae - induced colon tumorigenesis.