Inflammatory bowel disease (IBD) is a chronic and non-specific inflammatory disease of the intestine, including Crohn's disease (CD) and ulcerative colitis (UC), and its etiology remains unclear. In recent years, with changes in people's living environment and dietary habits, and the improvement of diagnostic levels, the incidence of IBD worldwide has been increasing rapidly, placing pressure on the medical system, and making the situation more severe. The diversity and stability of intestinal microorganisms are important factors influencing IBD, and the development of IBD therapeutics based on microorganisms has potential. Many researchers are developing engineered strains of bacteria for the treatment of IBD, and most of the research is still in the pre-clinical stage.
Transforming growth factor beta 1 (TGF-β1) is an important growth factor for intestinal epithelial cells, and many studies have confirmed its potential as a target for IBD therapy. Scientists cloned the sequence encoding the TGF-β1 gene into the downstream of the Bacteroides ovatus chitosanase promoter in a chitosan manipulator, constructing an engineered strain named BO-TGF. This engineered strain can synthesize and deliver TGF-β under the inducement of chitosan, accelerating the healing of damaged colon epithelium, reducing infiltration of inflammatory cells and expression of pro-inflammatory cytokines, and promoting the production of goblet cells rich in mucin. This engineered strain significantly improved the clinical symptoms of mouse colitis.
Cystatin in the nematode Acanthocheilonema viteae (AvCys) is an effective candidate for the treatment of IBD. By genetically modifying Escherichia coli ECN, researchers constructed an engineered strain named EcN-AvCys. This engineered strain can improve intestinal epithelial barrier function in pig tissues and human cell cultures, significantly inhibit mouse colitis models and post-weaning piglet intestinal inflammation.
Elafin is a natural protease inhibitor expressed in healthy gut mucosa with multi-effect anti-inflammatory characteristics in vitro and animal models. Studies have shown that Elafin expression in mucosa decreases in IBD patients. Researchers constructed a recombinant Lactococcus lactis (LAB) strain expressing Elafin. Oral ingestion of this engineered LAB in acute and chronic colitis mouse models helps restore intestinal homeostasis, reduce intestinal permeability, and cytokines and chemokines released from inflammatory epithelial cells, thereby preventing the occurrence of inflammatory bowel disease.
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