Probiotics, a kind of beneficial microorganism in the intestinal tract, have been widely used for the treatment of various diseases, including rheumatism, aging, inflammation, cancer, obesity, hypertension, diabetes and so on. In particular, several naturally occurring commensal probiotics have been explored as therapeutics for inflammatory bowel disease (IBD) treatment. Moreover, genetically engineered probiotics that sustainably secrete biologic drugs such as cytokines and therapeutic enzymes locally in the colon have also been reported. Although high efficacy has been achieved in animal models, there are still many concerns, such as limited concentrations of therapeutics at the site of disease, low potency, and inability of probiotics in the gastrointestinal tract due to the existence of gastric acid and bile salts. Therefore, genetically engineered probiotics that could be delivered effectively and continuously produce therapeutics have continued to fuel interest in microbes for the treatment of IBD.
Recently, Prof. Zhuang Liu and Prof. Qian Chen of our Institute developed an orally programmable probiotic for enhanced IBD treatment following scavenging of reactive oxygen species at the site of intestinal inflammation. Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) to scavenge reactive oxygen species, therefore improving the treatment of intestinal inflammation. To improve the bioavailability of ECN-pE in the gastrointestinal tract, chitosan and sodium alginate, effective biofilms, were used to coat ECN-pE via a layer-by-layer electrostatic self-assembly strategy. In a mouse IBD model induced by different chemical drugs, chitosan/sodium alginate coating ECN-pE (ECN-pE(C/A)2) effectively relieved inflammation and repaired epithelial barriers in the colon. Such engineered EcN-pE(C/A)2 could also regulate the intestinal microbial communities and improve the abundance of Lachnospiraceae_NK4A136 and Odoribacter in the intestinal flora, which are important microbes to maintain intestinal homeostasis. Thus, this study lays a foundation for the development of living therapeutic proteins using probiotics to treat intestinal-related diseases. The relevant results were published online June 14, 2022 in Nature Communications (Nat. Commun. 13, 3432 (2022)). PhD Jun Zhou is the first author of this paper.
Link to paper: https://www.nature.com/articles/s41467-022-31171-0
Title：Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery
Authors：Jun Zhou, Maoyi Li, Qiufang Chen, Xinjie Li, Linfu Chen, Ziliang Dong, Wenjun Zhu, Yang Yang*, Zhuang Liu* & Qian Chen*
Acknowledgement：This work was partially supported by grants from the National Research Programs of China (2020YFA0211100, 2021YFF0701800), the National Natural Science Foundation of China (91959104, 21927803, 51903182, 52032008), the Natural Science Foundation of Jiangsu Province (BK20190826), the China Postdoctoral Science Foundation (2020M671584), the Postdoctoral Science Foundation of Jiangsu Province (2020Z347), Suzhou Key Laboratory of Nanotechnology and Biomedicine, Collaborative Innovation Center of Suzhou Nano Science and Technology, and the 111 Program from the Ministry of Education of China.
Editor: Guo Jia