ZnO-Cu/Mn nanozyme for rescuing the intestinal homeostasis in Salmonella-induced colitis

Salmonella is one of the most common foodborne pathogens, which can cause severe enteritis and intestinal microbiota imbalance. However, there are limited strategies currently available for preventing or treating Salmonella-induced colitis. Herein, we developed the Cu/Mn-co-doped ZnO tandem nanozyme (ZnO-CM) with pH-responsive multienzyme-mimicking activities via doping engineering for the treatment of Salmonella-induced colitis. Benefiting from the co-doping of Cu and Mn, ZnO-CM nanospheres exhibit remarkable peroxidase-like activity in acidic condition and superoxide dismutase- and catalase-like activities in neutral environment. Animal experiments show that ZnO-CM can efficiently inhibit bacterial growth, alleviate inflammation, and restore the intestinal barrier, resulting in good antibacterial and anti-inflammatory effects on Salmonella-induced colitis. Mechanistically, ZnO-CM functions through inhibiting the continuous accumulation of ROS, increasing the levels of tight junction proteins occludin and claudin-1, and decreasing the expression of pro-inflammatory cytokines IL-1β and IL-6 in intestine. This work not only presents an effective paradigm for Salmonella-induced colitis therapy, but also provides new sights into the prevention and treatment of other bacterial enteritis.