Genetically engineered Bacillus subtilis-derived extracellular vesicles Alleviates Ulcerative colitis by restoring intestinal barrier and regulating gut microbiota

文献类型： 外文期刊

第一作者： Chen, Jiali

作者： Chen, Jiali;Wei, Chaozhi;Pan, Chunqiang;Wei, You;Li, Baoxian;Liu, Tao;Wang, Xiao;Wen, Zhengshun;Zhao, Yao;Zhang, Mengyu;Cheng, Jintao;Jin, Yuanxiang;Yang, Guiling;Chen, Jiali;Pan, Chunqiang;Wei, You;Li, Baoxian;Jin, Yuanxiang;Yang, Guiling

作者机构：

关键词： Bacterial extracellular vesicles; Surface display; Antimicrobial peptide; Inflammatory bowel disease; Akkermansia

期刊名称：CHEMICAL ENGINEERING JOURNAL （ 影响因子：13.2； 五年影响因子：13.5 ）

ISSN： 1385-8947

年卷期： 2025 年 512 卷

页码：

收录情况： SCI

摘要： Ulcerative colitis (UC) is evolving into a global burden for the increasing incidence recently. However, current therapeutic agents are not applicable due to limited efficacy and side effects. Bacterial extracellular vesicles (bEVs) arise booming interests in recent years for they contain a diverse range of bioactive substances from parental cells, and can facilitate intercellular communications. Herein, we utilized surface display technology to fuse antimicrobial peptide Cathelicidin-BF (Cathe), which had a broad-spectrum antibacterial activity, with Bacillus subtilis 168 spore protein CotC which enabled Cathe to further localize in BS168-derived EVs. Genetically engineered EVs displayed a strong stability against simulated digestive juice in vitro and mainly accumulated in the gastrointestinal tract after oral gavage to mice. Moreover, CotC-Cathe EVs (CEVs) exhibited dramatically enhanced ability compared with BS168 wild type (WT)-derived EVs (WEVs) in a dextran sulfate sodium (DSS)induced mice acute colitis model by inhibiting the inflammatory responses, restoring the impaired intestinal barriers and modulating gut microbiota. Interestingly, CEVs could greatly enrich the abundance of a well-known probiotic Akkermansia, and in our in vitro experiment, we found that Akkermansia can realize selective uptake of CEVs, indicating that CEVs could regulate the gut microbiota by interacting with Akkermansia. Our findings revealed for the first time that, CotC could be used to co-localize multiple functional heterologous proteins in BS168 EVs, given the outstanding therapeutic effects of CEVs, we emphasized the potential of CEVs as a novel, genetically engineered, and targeted agent, offering a promising therapeutic approach for managing various diseases.

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