Probiotic “backpacks” for treating inflammatory bowel disease

Like elite firefighters heading into the wild to fight an uncontrolled fire, probiotic bacteria do a better job of suppressing intestinal inflammation when equipped with the best equipment.

A new study by University of Wisconsin-Madison researchers shows the promise of some well-equipped gut-friendly bacteria for improving the treatment of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis.

Led by Quanyin Hu, a biomedical engineer and professor at the UW-Madison School of Pharmacy, the research builds on technology the team previously developed. This earlier technology encloses beneficial bacteria in a very thin protective shell to help them survive attack by stomach acid and competing microbes long enough to establish and multiply in the gut of mice.

While technology is making orally administered probiotics more effective, IBD is a complex disease that usually affects more than just imbalanced microbial communities in the gut.

“IBD is a complicated disease and you have to attack it from different angles,” says Hu.

So Hu and his colleagues designed specialized nanoparticles to neutralize molecules involved in IBD. They also found a way to attach these nanoparticle “backpacks” to beneficial bacteria after they’ve been encased in the protective layer.

Combined with the probiotics themselves, these nanoparticle backpacks could greatly improve — and simplify — IBD treatments.

While the actual causes of IBD are complex and still under investigation, one culprit is the overproduction of molecules known as reactive oxygen species. These molecules are critical to certain human bodily functions, but too many of them in the gut can fuel harmful inflammation along the gut lining.

Enter the nanoparticle backpacks. The tiny particles consist partly of sulfide and partly of hyaluronic acid. The acid is a powerful anti-inflammatory and the sulfide directly targets the reactive oxygen species.

Conducted on mice, Hu’s latest research shows that probiotic bacteria Escherichia coli Nissle 1917s in a protective case and equipped with the nanoparticle backpacks are significantly better at relieving IBD symptoms than their counterparts without the additional equipment. The findings were published Nov. 11 in the journal Science Advances.

The researchers estimated the effects of the treatments in two ways: by measuring changes in weight and changes in colon length in mice with IBD that received and did not receive the treatment.

Like humans, mice with IBD often experience weight loss and colon shortening as the disease progresses. Hu and his colleagues found that mice that received the full treatment had the least weight loss and much less colon shortening than their counterparts that received partial or no treatment.

Current treatment options depend on the stage and severity of the disease, while Hu and his colleagues say they have been looking for a more holistic treatment that could be effective at any stage.

“This is the most exciting part of this research for me,” says Hu. “We didn’t want to target a specific IBD stage. We wanted to select the most important factors that contribute to the cure or treatment of the disease at each stage.”

Additionally, the treatment is administered orally, which could make it a great-tasting alternative to other more invasive forms of IBD treatment, such as B. the partial or complete removal of the colon.

Although the results are promising, it will be some time before the treatments are tested in humans.

Next, Hu plans to test whether the nanoparticle backpacks work well with other types of probiotic bacteria and document whether the treatment has any unwanted side effects. Simplifying the manufacturing and attachment process of the nano-backpacks will also be crucial to making the treatments clinically feasible.

Relation: Liu J, Wang Y, Heelan WJ, Chen Y, Li Z, Hu Q. Mucoadhesive probiotic backpacks containing ROS nanoscavengers improve bacteriotherapy in inflammatory bowel disease. science adv. 2022;8(45):eabp8798. doi: 10.1126/sciadv.abp8798

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