To this end, Prof. MAO Zhengwei at the Zhejiang University Department of Polymer Science and Engineering collaborated with Prof. CHEN Xiaoyuan at the National University of Singapore and Prof. WANG Weilin at the Second Affiliated Hospital of the Zhejiang University School of Medicine in pioneering the development of artificial-enzyme-armed Bifidobacterium longum (BL) probiotics for reshaping a healthy immune system in inflammatory bowel disease. Their findings were published in Nature Nanotechnology. 

Fig. 1: BL@B-SA is composed of artificial enzymes (Fe SA), BL probiotics and linkers (C18–PEG-B) to conjugate them.

Probiotics are oxygen-intolerant. The researchers at Zhejiang University analyzed BL, a common type of probiotics, and found that it couldn’t autonomously scavenge reactive oxygen species (ROS) for lack of a series of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT).
“We took a bold move in combining these antioxidant enzymes with probiotics in an artificial fashion so that probiotics could autonomously metabolize toxic substances into non-toxic products,” MAO Zhengwei introduced. “This strategy can effectively improve the survival of probiotics in the inflamed intestine and fulfill the functions of maintaining the balance of the gut microbiota and repairing the intestinal mucosal tissue”.
To achieve this goal, MAO Zhengwei’s group and CHEN Xiaoyuan’s group employed the Fe/C-based single-atom nanozyme (B-SA) and designed the first probiotics / nanozyme composite. This novel “armor” empowers probiotics to defend better against the “bullets (ROS)” in the immune response.
The researchers modified the phenylboronic acid functional group on B-SA and took advantage of the supramolecular interaction between boronic acid and exopolysaccharides on the surface of bacteria to achieve the combination of B-SA and BL in mild conditions, thereby maximally preserving the activity of probiotics and artificial enzymes.

Structure and function diagram of the probiotics / artificial enzyme composite

In the follow-up study, MAO Zhengwei’s group and WANG Weilin’s group carried out validation experiments on both small-animal and large-animal models. They found that the probiotic / artificial enzyme composite performed better than the mixture of probiotics and artificial enzymes and drug combinations in clinical settings in treating inflammation and promoting the balance of the gut microbiota.
“To cure inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, it is of supreme importance to eliminate inflammation and restore the balance of the gut microbiota,” said WANG Weilin. “Our treatment strategy can serve dual purposes in this regard.”
Probiotic therapy has been adopted in clinical settings in China, the industrialization of probiotics has a solid foundation, and its safety has been verified. Featured by their remarkable safety, catalytic efficiency, stability and cost-effectiveness, nanozymes can also be mass-produced.
MAO Zhengwei is quite confident about the future of this study. “On the strength of the enormous potential of industrialization and the perfect safety of application, our team will strive to push the probiotics / artificial enzyme composite to clinical applications,” he said.