Bionic Dormant Body of Timed Wake-Up for Bacteriotherapy <i>in Vivo</i>

Abstract

The microorganism has become a promising therapeutic tool for many diseases because it is a kind of cell factory that can efficiently synthesize a variety of bioactive substances. However, the metabolic destiny of microorganisms is difficult to predict in vivo. Here, a timing bionic dormant body with programmable destiny is reported, which can predict the metabolic time and location of microorganisms in vivo and can prevent it from being damaged by the complex biological environment in vivo. Taking the complex digestive system as an example, the bionic dormant body exists in the upper digestive tract as a nonmetabolic dormant body after oral administration and will be awakened to synthesize bioactive substances about 2 h after reaching the intestine. Compared with oral microorganisms alone, the bioavailability of the biomimetic dormant body in the intestine is almost 3.5 times higher. The utilization rate of the oral bionic dormant body to synthesize drugs is 2.28 times higher than oral drugs. We demonstrated the significant efficacies of treatment using Parkinson’s disease (PD) mice by dormant body capable of timed neurotransmitter production after oral delivery. The timed bionic dormant body with programmable destiny may provide an effective technology to generate advanced microbial therapies for the treatment of various diseases.