Crohn's and probiotics: Scientists find way to kill bad gut bacteria, not the good

• Crohn’s disease and ulcerative colitis—two chronic inflammatory diseases of the gastrointestinal (GI) tract— affect at least 3 million people in the United States.
• Researchers in China have devised a microgel delivery system that can help boost the effect of probiotics in the gut while eliminating bad gut bacteria in people with Crohn’s and colitis.
• Using a mouse model, the scientists found that treated mice did not show damaged intestinal barriers or shortened colons, which are common symptoms of colitis.

Inflammatory bowel disease (IBD) is a chronic condition of the gastrointestinal (GI) tract. IBD includes Crohn’s disease and ulcerative colitis. An estimated 3 million people in the U.S. live with IBD, which has no known cure.

Research indicates a link between IBD and an imbalance of bacteria in the GI tract. This imbalance allows harmful bacteria to overrun the colon, reducing levels of potentially beneficial bacteria, and is thought to affect the intestinal barrier function and immune responses.

Immunosuppressants have long been the first line of defense in treatment. However, these medications are expensive and non-selective and are associated with a number of other undesirable side effects.

Experts have also explored the use of probiotics to improve IBD symptoms. However, it is challenging to deliver these bacteria to the site in the intestine where they are needed when taking them orally, due to the different, potentially bactericidal environments in the stomach and other parts of the digestive system.

Scientists at Zhengzhou University in China recently developed a probiotic-containing gel that can be taken orally, designed to shield the beneficial bacteria and disarm the bad.

Their research article covers these findings in ACS Central Science.

Roadblocks to improving IBD

Immunosuppressants have been the go-to medication for IBD, but they are known to cause severe side effects, including lowering the ability of your immune system to fight infections. Further, high costs keep these drugs out of reach for many people.

Newer therapies such as adalimumab have better outcomes, but cost remains an obstacle for them as well.

Researchers are now looking into oral probiotic therapies to treat and even prevent colitis. Delivering probiotics to the site where they are needed is far from an easy process, though.

Gastric acid and bile salts in the GI tract can kill off the good bacteria in probiotics before it settles in the gut. The nonstop contractions of the intestines can rush the probiotics out of the body as well.

Scientists have studied a variety of materials, including polymer gels, bacterial biofilms, and cell membranes, to overcome these roadblocks.

Recent innovations have focused on protecting probiotics in the GI tract. However, they have failed to address how the damaged tissues make the bad bacteria more welcome than the good.

The study’s authors stated: “The harsh physiological environment of the GI tract and, more importantly, the abnormal proliferation of E. coli during colitis limit probiotic colonization.”

Protecting probiotics in the gut

The researchers found that calcium tungsten microgels (CTM) can deliver probiotics to the sites most affected by problematic bacterial overgrowth in mice models with induced colitis and enable the probiotics to colonize the gut there.

The study’s authors discovered that CTM exerts “a protective effect” on probiotics in the GI environment. The microgels also help the probiotics remain in the intestine longer.

As the probiotics multiply in the gut, they help restore the richness and diversity in the GI tract and prevent the overgrowth of problematic bacteria, which prevent this.

The study’s methods

The Zhengzhou University team first fed mice with water or water containing dextran sulfate sodium (DSS). DSS was used to induce colitis symptoms.

The scientists placed nanoparticles containing sodium alginate, tungsten, and calcium into small microgels. Then, they coated the spheres with probiotic bacteria.

The team treated the mice with the microgels for five days, after which the animals were sacrificed.

Once the microgels arrived in the colon, calprotectin proteins, which are more abundant in people with IBD, bound to the calcium, breaking down the spheres.

The tungsten displaced molybdenum in the Enterobacteriaceae, inhibiting its growth without affecting the probiotics.

“This is because tungsten can replace molybdenum in molybdenum enzymes and inhibit the activity of Enterobacteriaceae-dependent molybdenum enzymes, whereas the growth of probiotics is not dependent on molybdenum enzyme, which means that CTM has a selective inhibitory effect,” the scientists noted.

The study’s results

In experiments with a colitis mouse model, the microgel delivery system allowed probiotics to populate in the GI tract without any adverse effects.

CTM reduced Enterobacteriaceae by 45 times and increased colonization of probiotics by 25 times.

Further, mice treated with the microgel spheres did not show many colitis markers, such as shortened colons or impaired intestinal barriers.

A new way to treat colitis?

The researchers concluded that CTM may be “a remarkable treatment for colitis, including restoration of colonic length, effective downregulation of the inflammatory response, restoration of the damaged mucosal barrier, and restoration of gut microbiome homeostasis.”

The authors believe that the current study offers a new perspective into therapies using colonizing probiotics. They hope to confirm their findings in more advanced preclinical studies.

Medical News Today discussed this research with Dr. Rudolph Bedford, a gastroenterologist at Providence Saint John’s Health Center in Santa Monica, California, who was not involved in the study.

Dr. Bedford felt that the present study is viable when it came to delivering good bacteria to the colon itself: “It looks as though it’s something that might hold some promise.”

However, he predicts that the next step of human trials “will take quite some time,” and likely years to complete.

He agreed that the gut’s bacterial flora is one of many factors that predispose people to developing IBD. He said that changing the microflora might be helpful for treating or preventing the condition in some people.

He also noted that drugs are not the only way to combat GI issues.

When asked about the role of diet in the progression of IBD, the gastroenterologist said: “There have been recent studies looking at the diet, realizing that things that promote healthy bacterial flora may also change the course of the disease […] in terms of treatment and keeping the disease in remission.”

Dr. Bedford acknowledged that commonly prescribed antibiotics change the intestinal flora and make harmful bacteria resistant to the antibiotics themselves.

Maintaining a healthy gut requires not only limiting antibiotics, he said, “But you want to make sure that you have good bacteria within the system in any way possible – either by diet and in some instances, by taking probiotics.”

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