Antibodies that coat the gut slow the cell growth that can lead to colon cancer, a mouse study finds; mice without them grew twice as many tumors

Antibodies that coat the inside of the gut help keep its lining cells from dividing too fast, which may help prevent colon cancer, according to a mouse study published Nov. 11 in the journal Nature by researchers at Rockefeller University in New York.  Mice that lacked the antibodies grew more than twice as many colon tumors, the university said.

The antibody is immunoglobulin A, or IgA, the body’s most common type of antibody.  The gut makes large amounts of it.  About 1 in 500 people in the U.S. have IgA deficiency, meaning they make little or none, and they are known to face a higher risk of colorectal cancer, said Gregory Donaldson, the study’s first author, now an assistant professor at UCLA.  The study offers an explanation for that link.

What it found

• When IgA-deficient mice were given IgA by mouth, their extra tumor risk went away.
• IgA works by sticking to DMBT1, a protein on the surface of gut-lining cells.  When gut bacteria are present, DMBT1 acts like a gas pedal for cell division, and IgA acts as the brake.
• The protection came from the antibody’s basic shape, not from it grabbing any particular germ, the paper says.
• Removing the signaling part of DMBT1 in IgA-deficient mice reversed both the faster cell division and the higher tumor risk.

Can IgA deficiency be treated?

Not directly, for now.  The ideal treatment would be to replace the missing IgA, but no IgA-enriched antibody product is available in the U.S., according to the Immune Deficiency Foundation, a patient group.  Doctors instead treat the problems the condition causes, such as antibiotics for repeated ear, sinus and lung infections.  Many people with IgA deficiency have no symptoms and don’t know they have it until a blood test finds it, the foundation says.  Some people who also lack a type of IgG antibody and have serious repeated infections may get standard antibody replacement, which contains only traces of IgA.

What it could mean for future treatment and prevention

In the mice, IgA given by mouth was enough to erase the extra tumor risk, which hints that an oral IgA treatment could one day stand in for the missing antibody.  The paper found that the protection came from the antibody’s basic shape, not from it targeting any particular germ.  The study also names DMBT1 as a possible target.  “Perhaps we could influence epithelial cells to be less likely to develop into a tumor,” Mucida said, referring to the cells lining the gut, and the university said the findings could matter even for otherwise healthy people.

The researchers see the most promise in prevention after polyps are removed, since “right now, there are no interventions available at that point,” Mucida said.  Donaldson said his team has some evidence that certain gut bacteria act like IgA, which could lead to a probiotic that boosts protective IgA, an idea he called “very speculative.”

Limits

The work was done in mice and in lab-grown cells, not people.  No treatment based on it has been tested in humans.  For now, standard colon cancer screening, such as colonoscopy or stool tests, remains the proven way to find and remove polyps early.

Source:  Donaldson et al., “Suppression of epithelial proliferation and tumorigenesis by IgA,” Nature, Nov. 11, 2026; Rockefeller University news release, Nov. 11, 2026; Immune Deficiency Foundation, “Selective IgA deficiency”.