An oral “Super probiotics” with versatile self-assembly adventitia for enhanced intestinal colonization by autonomous regulating the pathological microenvironment

Abstract

Transplanting beneficial bacteria to gut microbiome can positively modulate microbiome composition and is a promising strategy to prevent and treat diseases. However, oral probiotic delivery is challenged not only by the physiological microenvironment, but also by pathological microenvironment. Herein, we designed a Super Gut Microorganism (SGM) encapsulated with versatile self-assembly coating for enhanced intestinal colonization. SGM has a rapidly self-assembling coating of tannic acid and poloxamer 188 that not only resists the attack of the physiological microenvironment but more importantly, autonomously modulates the pathological microenvironment (e.g., scavenging inflammation-mediated ROS and taking iron away from pathogenic bacteria), which improves probiotic survival. In addition, the artificial coat mediates strong intestinal mucosal adhesion, enhancing the intestine colonization of probiotics especially in disease. SGM significantly improved the efficacy in the prevention and treatment of colitis in vivo. In dextran sulfate sodium (DSS) colitis mice, SGM showed an excellent anti-inflammatory effect, capacity to restore intestinal barrier functions, and to prompt the balance of gut flora. In Salmonella enterica serovar Typhimurium (STm) colitis mice, treatment with SGM resulted in 6.8-times less STm compared to uncoated probiotics. The SGM presented here are a new resource to create novel probiotic systems to treat and prevent microbiome related diseases.