An engineered probiotic secreting Sj16 ameliorates colitis via Ruminococcaceae/butyrate/retinoic acid axis
| Autor: | Lichao Zhang, Ruibing Yang, Xi Sun, Yao Liao, Zifeng Zhu, Lifu Wang, Zhongdao Wu |
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| Rok vydání: | 2021 |
| Předmět: |
colitis
Biomedical Engineering Retinoic acid Pharmaceutical Science RM1-950 Butyrate medicine.disease_cause Inflammatory bowel disease Ruminococcaceae/butyrate/retinoic acid axis law.invention chemistry.chemical_compound Probiotic Chemical engineering law engineered probiotic medicine Colitis Sj16 Escherichia coli Research Articles Gastrointestinal tract Treg/Th17 balance business.industry medicine.disease chemistry Cancer research TP155-156 Therapeutics. Pharmacology business TP248.13-248.65 Research Article Biotechnology Ruminococcaceae |
| Zdroj: | Bioengineering & Translational Medicine, Vol 6, Iss 3, Pp n/a-n/a (2021) Bioengineering & Translational Medicine |
| ISSN: | 2380-6761 |
| DOI: | 10.1002/btm2.10219 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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