Open AccessAn engineered probiotic secreting Sj16 ameliorates colitis via Ruminococcaceae/butyrate/retinoic acid axis
Author(s) -
Wang Lifu,
Liao Yao,
Yang Ruibing,
Zhu Zifeng,
Zhang Lichao,
Wu Zhongdao,
Sun Xi
Publication year - 2021
Publication title -
bioengineering and translational medicine
Language(s) - English
Resource type - Journals
ISSN - 2380-6761
DOI - 10.1002/btm2.10219
Subject(s) - colitis , butyrate , probiotic , gastrointestinal tract , inflammatory bowel disease , retinoic acid , microbiology and biotechnology , sodium butyrate , immunology , pharmacology , medicine , chemistry , biology , bacteria , biochemistry , disease , fermentation , gene , genetics
Most inflammatory bowel disease (IBD) patients are unable to maintain a lifelong remission. Developing a novel therapeutic strategy is urgently needed. In this study, we adopt a new strategy to attenuate colitis using the Escherichia coli Nissle 1917 probiotic strain to express a schistosome immunoregulatory protein (Sj16) in the gastrointestinal tract. The genetically engineered Nissle 1917 (EcN‐Sj16) highly expressed Sj16 in the gastrointestinal tracts of dextran sulfate sodium‐induced colitis mice and significantly attenuated the clinical activity of colitis mice. Mechanistically, EcN‐Sj16 increased the intestinal microbiota diversity and selectively promoted the growth of Ruminococcaceae and therefore enhanced the butyrate production. Butyrate induced the expression of retinoic acid, which further attenuated the clinical activity of colitis mice by increasing Treg cells and decreasing Th17. Strikingly, retinoic acid inhibitor inhibited the therapeutic effects of EcN‐Sj16 in colitis mice. These findings suggest that EcN‐Sj16 represents a novel engineered probiotic that may be used to treat IBD.