Cancers May Be Prevented Through Reinforcement of the Intestinal Barrier

Having a weak intestinal barrier may be the cause of cancers forming elsewhere in the body. This is according to a new study published in PLoS ONE by Thomas Jefferson University researchers.

It appears that the hormone receptor guanylyl cyclase – a previously identified tumor suppressor that exists in the intestinal tract – has an important role in reinforcing the body’s intestinal barrier, which helps separate the gut from the rest of the body, potentially keeping cancer away. Without this receptor, the barrier can break down.

Led by Scott Waldman, M.D., Ph.D., a team of researchers found in a pre-clinical study that suppressing guanylyl cyclase in mice compromised the strength of the intestinal barrier. The resulting problems included inflammation and cancer causing agents leaking out of the gut, damaging DNA and forming cancer outside the cavity, including in the liver, lung and lymph nodes. However, stimulating this hormone receptor in mice had the opposite effect; it reinforced the intestinal barrier opposing these pathological changes.

A weakened intestinal barrier has been linked to numerous diseases, including inflammatory bowel disease, food allergies, and asthma. However, this study gives new evidence that guanylyl cyclase has a prominent role in maintaining the strength of the intestine wall. The research team believes strengthening this hormone receptor could aid in protecting individuals from inflammation and cancer in the rest of the body.

The role of guanylyl cyclase outside the area of the intestine has been mostly a mystery. Dr. Waldman and his team have previously demonstrated its role as a tumor suppressor and biomarker that can reveal metastases in the lymph nodes. They’ve used it to predict cancer risk, and have even found it to be correlated with obesity.

A new drug that contains guanylyl cyclase is close to landing on the pharmaceutical market, however its main purpose is to treat constipation. This study will help pave the way for future clinical studies to investigate the hormone receptor’s abilities beyond treatments in humans, including prevention and treatment of inflammatory bowel disease and cancer.

Dr. Waldman concludes, "We've shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer. And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier. Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier."


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