Engineered Probiotics Target Proinflammatory Molecules and Improve Ulcerative Colitis Symptoms

Stomach acid interferes with the effectiveness of probiotics taken as pills. Researchers are bioengineering probiotics in hopes of getting around that problem.

Ulcerative colitis is a chronic inflammatory disease characterized by defects in the colon epithelial tissue and abnormal response from inflammatory cytokines. The causes of the disease are complex, but one culprit is believed to be an overproduction of reactive oxygen species (ROS). In normal amounts, ROS is necessary for regular physiologic functions. However, an abundance of this molecule promotes damaging inflammation of the colon epithelium.

A recent study published in Science Advances that was led by University of Wisconsin-Madison School of Pharmacy professor Jun Liu demonstrates how a biomedically engineered probiotic might improve treatment for inflammatory bowel diseases, a group of diseases that includes ulcerative colitis. Probiotics pills can help treat ulcerative colitis by helping restore protective gut flora. The problem with oral probiotics is that stomach acids and other harsh factors make it difficult for these probiotics to remain in the gastrointestinal tract long enough to establish in the gut and produce reliable therapeutic effects.

Liu and colleagues engineered an encapsulated oral probiotic that protects it from the harsh GI environment and enhances its adhesion to the colon mucosal membrane. In addition, Liu and the study researchers developed nanoparticles of a conjugate of hyaluronic acid (HA) and poly (propylene sulfide) (PPS), which they piggybacked to the encapsulated probiotic. The hyaluronic acid acts as an anti-inflammatory agent, and the sulfide scavenges and consumes ROS in the inflamed colon.

When tested in an animal model, the researchers found that the engineered HA-PPS conjugate probiotic was more effective at relieving IBD symptoms compared with probiotics without the added conjugate.

Liu and colleagues used the probiotic bacteria ­Escherichia coli Nissle 1917 for this study. Before the engineered probiotic is tested in humans, they recommend evaluating other beneficial bacteria carriers, because some E. coli strains may be associated with colon cancer.