Oral probiotics have always been one of the best ways to regulate immune system function and intestinal flora balance, but the effect of probiotics is often compromised by the unique pathological microenvironment of the inflamed gut.
On March 27, Nature Nanotechnology reported online on new results for the solution. Professor Mao Zhengwei of the Department of Polymers of Zhejiang University, together with Professor Chen Xiaoyuan of the National University of Singapore and Professor Wang Weilin of the Second Affiliated Hospital of Zhejiang University School of Medicine, represented by bifidobacteria required by the human body, constructed a probiotic/artificial enzyme composite material for the first time, which effectively improved the survival and proliferation of probiotics in the inflammatory microenvironment of oxidative stress, thereby improving its colonization and flora regulation ability in the inflammatory intestine, and providing a new strategy for the treatment of enteritis.
Schematic diagram of structure and function of probiotic/artificial enzyme composites. (Photo courtesy of the research group)
The body’s probiotics are known as the “guards” stationed in the gut, and when the body’s immune system fights harmful bacteria, they do their part.
Oral probiotics must first resist the erosion of stomach acid, bile and other substances before they can safely reach the intestines. Previous scientists have aimed to use “armor” to form a physical barrier on the surface of probiotics.
Whenever encountering menacing aggression, harmful bacteria will secrete a large number of harmful substances to make probiotics lose vitality. Immune cells are sterilized by releasing large amounts of reactive oxygen species, while also causing probiotics that cannot adapt to oxidative stress to wither.
To this end, how to save probiotics from war and better play their effectiveness has become a breakthrough in the research of the Zhejiang University team.
Probiotics are not oxygen tolerant, and researchers at Zhejiang University, represented by bifidobacteria common in probiotics, found that they could not independently remove reactive oxygen radicals due to the lack of a series of metabolic enzymes such as superoxide dismutase and catalase.
“We boldly envision artificially combining these metabolic enzymes with probiotics, so that probiotics can autonomously metabolize toxic substances into non-toxic products.” Mao Zhengwei introduced that this strategy can effectively improve the survival of probiotics in the inflammatory intestine, play a role in maintaining the balance of intestinal flora, repair intestinal mucosa and other functions.
To this end, Mao Zhengwei and Chen Xiaoyuan’s team selected Fe/C-based single-atom nanoenzymes (B-SA) with multi-enzyme catalytic function to construct probiotic/nanozyme active composites for the first time, and the development of new armor allows probiotics to better resist the “fire” of immune response.
How to put this new armor on probiotics?
Mao Zhengwei’s team modified the phenylboronic acid group on B-SA, and used the supramolecular interaction of boric acid and polysaccharide o-diol on the surface of bacteria to realize the recombination of B-SA and bifidobacteria under mild conditions, and preserved the activity of probiotics and artificial enzymes to the greatest extent.
In the follow-up study, Mao Zhengwei and Wang Weilin teamed up to carry out confirmatory experiments in colitis models of a variety of small animals and large animal models of beagles. They found that probiotic/artificial enzyme composites had better inflammatory treatment and intestinal flora balance than probiotic and artificial enzyme mixtures and clinical first-line drug combination therapy.
“To cure intestinal inflammation, including irritable bowel syndrome, ulcerative colitis, Crohn’s disease, etc., the main thing is to eliminate inflammation and restore the balance of the intestinal flora.” Wang Weilin said, “Our treatment strategy can simultaneously eliminate inflammation and restore the balance of intestinal flora. ”
From the domestic situation, probiotic therapy has entered the clinic, the industrialization of probiotics has a solid foundation, and its safety has also been verified. For nanozymes, they have the characteristics of safety, high catalytic efficiency, stability, economy and large-scale preparation, and can also achieve stable mass production.
Therefore, Mao Zhengwei is full of confidence in the future of this research. He said that based on the industrialization potential and application safety, the team will actively promote probiotic/artificial enzyme composites to clinical applications. (Source: Cui Xueqin, China Science News)
Related paper information:https://doi.org/10.1038/s41565-023-01346-x
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