Hydrogels of diet-derived electron donors restore epithelial hypoxia and reduce iNOS synthesis to inhibit inflammation-induced overgrowth of facultatively anaerobic bacteria for gut homeostasis

Food hydrogels targeting respiration of microorganisms via changing the micro-ecological environment in gut were prepared through the self-assembly of polyphenols extracted from tea leaves harvested in summer and autumn and the protein fibrils originating from egg white lysozyme. Oral administration with the hydrogels effectively inhibited the over-expansion of the facultative anaerobic bacterium indicated by E. coli Nissle 1917 (EcN) and alleviated the clinic symptoms of chronic intestinal inflammation in mice. Importantly, the hypoxia of epithelial cells was elevated significantly and the overexpression of the inducible NO synthase (INOs)-related NOS2 gene was inhibited substantially in colons of the colitis mice, which accounted for prevention of the abnormal expansion of E. coli via blocking respiration. The treatment with the hydrogels preserved normal mitochondrial function in colonic epithelial cells under oxidative stress, which could serve as the mechanism to maintain the capability to consume oxygen.