Scientists Discover Major Cause Of Inflammatory Bowel Disease

By Roni Dengler | September 18, 2018 2:30 pm
IBS stomach pain how it works IBD

Irritable bowel Disease is a painful syndrome that affects the intestines. Scientists say they’ve discovered a major driver of the disease. (Credit: RomarioIen/shutterstock)

Researchers have identified a prime culprit behind inflammatory bowel disease, or IBD, an incurable disorder that causes abdominal pain, diarrhea and weight loss from malnutrition. The discovery also reveals a pathway to treatment, scientists report today in the journal Cell Reports.

“We were able to block the inflammation, basically block IBD,” said Ze’ev Ronai, a biologist at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, who led the new research.

IBD Digestive Discomfort

At least three million people across the U.S. suffer from Crohn’s disease or ulcerative colitis, the two main types of inflammatory bowel disease. The disorders affect the digestive tract and lining of the gut, where inflammation causes cramps, constipation and rectal bleeding. Fever, fatigue and appetite loss often accompany the conditions. Although there is no cure, scientists think genetics, the gut microbiome and the immune system may all play a role. But a clear cause eluded them until Ronai and his team landed on a suspect while examining an unrelated phenomenon.

Ronai’s lab studies the processes cells use to bounce back from stress. Since a gene called RNF5 is a key player in these activities, the scientists suspected that disrupting its function in mice would reveal major new insights. So, a decade ago, the team created mice that lack RNF5.

“To our great surprise, these mice did not appear to have any significant [traits],” said Ronai. “We even called them ‘the boring mice’.”

But the researchers did notice that the intestines of these mice were inflamed — not enough to cause big problems, but enough to keep an eye on. That baseline inflammation led the scientists to ask what would happen if they triggered more inflammation in the animals’ guts, similar to how dairy or fried and spicy foods can elicit inflammatory bouts in people with IBD.

Ze'ev Ronai of Sanford Burnham Prebys Medical Discovery Institute

Ze’ev Ronai led the team behind the IBD breakthrough. (Credit: Sanford Burnham Prebys Medical Discovery Institute)

Inflamed Intestines

So, the researchers added a compound that causes gut inflammation in mice called DSS to the rodents’ drinking water. The drug usually causes mild intestinal inflammation in healthy mice and they recover within a couple of weeks. But the mice without RNF5 responded much more severely. They developed acute colitis with all the symptoms people have. Close to 50 percent of the animals died within a few weeks.

“These animals are super sensitive to inflammation,” Ronai said.

RNF5’s usual job is to flag cellular garbage for disposal. When the researchers went looking for proteins in intestinal cells RNF5 might mark as trash, they found one called S100A8, an FDA-approved marker for measuring severe colitis. The mice without RNF5 not only had high amounts of S100A8 in their intestinal cells, but also in their blood.

And then when Ronai and team gave the mice antibodies that neutralize S100A8, the rodents’ IBD symptoms disappeared.

What’s more is that the ratio of low RNF5 and elevated S100A8 levels in mice matched that in human patients with IBD ,meaning doctors could use the protein levels as a blood test to identify patients for whom the treatment would work best.

The results “provide the justification and rationale to develop drugs against S100A8 that go to the clinic,” Ronai said.

CATEGORIZED UNDER: Health & Medicine
MORE ABOUT: personal health
  • Uncle Al

    Porcine whipworm proximate immunomodulation. Trichuris trichiura, Wikipedia. FDA-condemned for being safe and effective. And cheap.

  • Mavis

    Another Over hyped bit of rodent research. It is pretty clear that inflammation has a big role in IBD. There is also no evidence this will translate into human models. The media will pick up on this unfounded claims, and run with it. In Post fact America, science has been undermined by these clever attention, and funding seeking researchers. We are no closer to finding the underlying cause of this condition, but there is plenty of money in advertorials like this. Not much science here, just content and filler. This is typical of most of the health journalism, in support of varios industries that get what they pay for.

    • Notso Incognito

      Folks want to read about science discoveries before they are common knowledge. Exciting things found using mice are still exciting things.

      While I believe your “click-bait” accusations are fair in regards to media at large I don’t think they apply to science magazines or blogs. Like yourself, the rest of us that come here are savvy enough to know that rodent research is only pointing in a direction for further study; not an answer in itself.

      • Mavis

        Of course, but when the mass media gets hold of these. they take the word. mice out of the story and use the word cure.

    • mike

      This story relates observation that posits a hypothesis that doesn’t suggest broader application than the evidence suggests. Good science and science reporting. The story and subject aknowledge they are at the now-we-test-it-in-humans phase. I’m highly critical of claims and stories that exaggerate what a study or experiment determine, and I sympathize with criticism of the headline as overblown click bait. Still, the story itself is solid as is the science.

      • Mavis

        If we expend the energy to track this back we will find industry funding, and the use of this ‘research’ in a pharma marketing campaign. There is nothing “groundbreaking” here unless you are marketing something.

  • belli

    At least three million people across the U.S. suffer from Crohn’s disease or ulcerative colitis, the two main types of inflammatory bowel disease. So This is an great effort to improve mans health.

  • Mike Johnson

    If anyone cares and has access poor genetic variants can be limited and this will increasingly be the case over time. The best variant of RNF5 may be made available. Remember we look for continuous small improvement across our process and this sort of research may point the way toward better (not perfect) outcomes.


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