Like elite firefighters headed into the
wilderness to combat an uncontrolled blaze, probiotic bacteria do a better job
quelling gut inflammation when they’re equipped with the best gear.
A new study by researchers at the University
of Wisconsin-Madison demonstrates just how much promise some well-equipped
gut-friendly bacteria hold for improving treatments of inflammatory bowel
disease (IBD), including Crohn’s disease and ulcerative colitis.
Led by Quanyin Hu, a biomedical engineer and
professor in the UW-Madison School of Pharmacy, the research builds on
technology the team had previously designed. That prior technology encases
beneficial bacteria within a very thin protective shell to help them survive an
onslaught of stomach acids and competing microbes long enough to establish and
multiply in the guts of mice.
While the technology makes orally administered
probiotics more effective, IBD is a complex disease that usually involves more
than gut microbial communities that are out of whack.
“IBD is a complicated disease, and you
need to attack it at different angles,” says Hu.
So, Hu and his colleagues devised specialized
nanoparticles to neutralize molecules implicated in IBD. They’ve also figured
out a way of attaching these nanoparticle “backpacks” to beneficial
bacteria after encasing them in the protective coating.
Combined with the probiotics themselves, these
nanoparticle backpacks could significantly improve – and simplify – IBD
treatments.
While the root causes of IBD are complex and
still being studied, one culprit involves the overproduction of molecules known
as reactive oxygen species. These molecules are crucial for certain human body
functions, but too many of them in the gut can fuel damaging inflammation along
the lining of intestines.
Enter the nanoparticle backpacks. The tiny
particles are part sulfide and part hyaluronic acid. The acid is powerfully
anti-inflammatory, and the sulfide directly targets the reactive oxygen
species.
Conducted in mice, Hu’s latest research shows
that probiotic bacteria Escherichia coli Nissle 1917 encased in a protective
shell and outfitted with the nanoparticle backpacks are significantly better at
relieving IBD symptoms than their counterparts without the additional gear. The
findings were reported 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 the colon
length of mice with IBD that did and did not receive the treatment.
Like humans, mice with IBD commonly experience
weight loss and colon shortening as the disease progresses. Hu and his
colleagues found that mice that received the full treatment experienced the
least amount of weight loss and much less colon shortening than their
counterparts that received partial or no treatments.
Current treatment options depend on the stage
and severity of disease, whereas Hu and his colleagues say they have sought a
more holistic treatment that could be effective at any stage.
“That’s 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 curing
or treating the disease at whatever stage.”
Additionally, the treatment is administered
orally, which could make it a palatable alternative to other more invasive
forms of IBD treatment such as partial or complete remove of the colon.
While the results are promising, it will be
some time before the treatments are tested in humans.
Next in Hu’s sights is testing whether the
nanoparticle backpacks work well with other probiotic bacteria species and
documenting whether the treatment has any unwelcome side effects. Simplifying
the process of creating and attaching the nano-backpacks will also be crucial
for making the treatments clinically feasible.
Reference:
Quanyin
Hu et al,Mucoadhesive probiotic backpacks with ROS nano-scavengers enhance the
bacteriotherapy for inflammatory bowel diseases, Science Advances, DOI 10.1126/sciadv.abp8798