Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery

作者：

Jun Zhou¹, Maoyi Li¹, Qiufang Chen², Xinjie Li¹, Linfu Chen¹, Ziliang Dong¹, Wenjun Zhu¹, Yang Yang^3,*, Zhuang Liu^1,*, Qian Chen^1,*

单位：

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 215123 Suzhou, China

²Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, 230032 Hefei, Anhui, China.

³Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433 Shanghai, China

摘要：

Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS in the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb inflammatory bowel disease (IBD). Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) for 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. Unexpectedly, 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.

影响因子：

14.919

分区情况：

一区

链接：

https://www.nature.com/articles/s41467-022-31171-0