CHEMICAL SCIENCE

Artificial enzyme armed with Bifidobacterium longum probiotics to relieve intestinal inflammation and dysbacteriosis


On March 27, 2023, Professor Mao Zhengwei of Zhejiang University, Professor Chen Xiaoyuan of the National University of Singapore, and Professor Wang Weilin of the Second Affiliated Hospital of Zhejiang University School of Medicine published a paper entitled “Artificial-enzymes-armed Bifidobacterium longum probiotics for alleviating” in the journal Nature Nanotechnology intestinal inflammation and microbiota dysbiosis”.

The study reported anti-inflammatory artificial enzyme-armed Bifidobacterium longum probiotic (BL@B-SA50) to regulate intestinal inflammation. Among them, artificial enzymes can mimic the natural antioxidant defense system, quickly relieve inflammatory symptoms, not only replace clinically used anti-inflammatory drugs, but also protect probiotics from ROS damage and exert their probiotic functions. In addition, the colonizing properties of Bifidobacterium longum in the intestine ensure continuous antioxidant therapy of artificial enzymes at the site of disease. The engineered probiotics can alleviate intestinal inflammation, restore intestinal barrier function, increase the richness and diversity of intestinal flora, effectively treat UC and CD in mice and UC in dogs, and greatly accelerate its clinical transformation process.

The corresponding authors of the paper are Mao Zhengwei, Chen Xiaoyuan, Wang Weilin; The first author is Cao Fangfang.

Inflammatory bowel disease (IBD) is a class of chronic intestinal inflammation with recurrent characteristics, mainly including UC and CD phenotypes, affecting the health of millions of people every year. At present, the pathogenesis of IBD is not clear, but more and more studies have shown that the pathogenesis of IBD is related to factors such as intestinal dysbacteriosis, immune response disorders, and intestinal barrier damage. Currently, the traditional approach to treating IBD mainly uses drugs such as 5-aminosalicylic acid (5-ASA), corticosteroids, or immunosuppressive drugs to control inflammation, and probiotics as adjunctive therapy. However, on the one hand, anti-inflammatory drugs are metabolically unstable and lack targeting, which can lead to serious adverse drug reactions. On the other hand, anaerobic probiotics lack antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) and are susceptible to attack by reactive oxygen species (ROS) in IBD, resulting in poor therapeutic efficacy (Figure 1). There is a need for a more effective and safer way to treat IBD.

Figure 1: Clinical therapy for IBD versus probiotic therapy armed with artificial enzymes.

In view of this, the team of Professor Mao Zhengwei of Zhejiang University, Professor Chen Xiaoyuan of the National University of Singapore and Professor Wang Weilin of the Second Affiliated Hospital of Zhejiang University School of Medicine modified artificial enzymes with the ability to scavenge reactive oxygen species (ROS) onto Bifidobacterium longum probiotics, and constructed anti-inflammatory engineered probiotics (BL@B-SA50) to regulate intestinal inflammation. Probiotics armed with artificial enzymes consist of three parts, namely artificial enzymes, probiotics and linkers. Among them, the artificial enzyme, the research group selected the iron single atom catalyst Fe SA. Because Fe SA has strong antioxidant capacity compared to traditional nanoenzymes, it can quickly and effectively remove ROS, protect intestinal cells and probiotics. Probiotics, the study group selected Bifidobacterium longum probiotic BL. Because BL not only has a probiotic function conducive to IBD repair, but also is one of the few bacteria in probiotics with intestinal colonization ability, it can prolong the targeting and residence time of artificial enzymes loaded on its surface in the intestine, and continuously remove excessive ROS and inflammatory factors. The linker, the research group selected C18-PEG-B, whose hydrophobic end C18 can be modified on the surface of Fe SA through non-covalent interaction, while the phenylboronic acid end B can undergo a fast and simple boronic acid o-diol reaction with polysaccharides on the surface of the probiotic, modified on the BL surface, without affecting the survival rate of anaerobic BL.

Figure 2: Characterization of artificial enzyme-armed Bifidobacterium longum probiotics.

Figure 3: Antioxidant capacity test of artificial enzyme-armed Bifidobacterium longum probiotics.

Figure 4: Gastrointestinal stability and targeting of probiotics armed with artificial enzymes.

Figure 5: UC of artificial enzyme-armed probiotic-treated mice.

Figure 6: CD of artificial enzyme-armed probiotic-treated mice.

Figure 7: UC of probiotic therapy dogs armed with artificial enzymes.

The results show that the engineered probiotic can relieve intestinal inflammation, restore intestinal barrier function, increase the richness and diversity of intestinal flora, effectively treat UC and CD in mice and UC in dogs, and greatly accelerate its clinical transformation process. (Source: Science Network)

Related paper information:https://doi.org/10.1038/s41565-023-01346-x



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