Gastric Bypass Surgery Potentially Lowers Intestinal Cancer Risk

A widely recognized form of weight loss surgery may lower the risk of colorectal cancer by changing the levels of bile acids in the bloodstream. These findings could pave the way for new bowel cancer treatments.

During gastric bypass surgery, the stomach is surgically altered to create a small upper pouch and a larger lower pouch. The small intestine is then connected to the upper pouch, allowing food and digestive juices to bypass most of the upper stomach and small intestine. Post-surgery, patients often feel fuller and experience quicker weight loss.

Earlier research indicated that this procedure is associated with a decreased risk of colorectal cancer; however, the underlying reasons remained unclear. To investigate further, Rebecca Kesselling of the University of Freiburg, Germany, and her team fed mice a high-fat diet until they reached approximately 50% of their starting weight. They then performed a partial gastric bypass on some of the mice, while the remaining mice underwent a sham surgery that did not alter their digestive systems.

To isolate the weight-loss effects of gastric bypass surgery, the team grouped the gastric bypass mice alongside half of the sham-operated mice. Over six weeks, the gastric bypass mice lost about 20% of their body weight on average.

Subsequently, the researchers implanted colorectal cancer cells into the colons of the mice. After an additional six weeks, it was observed that colon tumors in the gastric bypass mice were two-thirds smaller than those in the mice that either continued gaining weight or lost weight solely through diet.

Additionally, cancer spread to the liver was seen in only one out of twenty gastric bypass mice, while it occurred in most of the sham-operated mice.

“Both sham groups exhibited similar tumor levels, but weight loss alone could not account for the lower cancer risk, suggesting that gastric bypass involves additional factors,” Kesselling explains.

The researchers speculated that this might be attributed to alterations in bile acids, which are compounds that aid in fat digestion. These molecules are typically produced by the liver, move through the gallbladder, stomach, and small intestine, and then return to the liver via the bloodstream.

“Bile acids are reintroduced into the small intestine during bypass surgery,” Kesselling states, implying that this process may lead to variations in intestinal bacteria that chemically modify these molecules.

The mice that underwent gastric bypass surgery displayed lower levels of specific bile acids, known as primary bile acids, in both their colon and bloodstream compared to the sham group.

To further explore whether changes in bile acids influenced cancer risk, the team conducted a similar experiment with another group of mice. Instead of gastric bypass, these mice had surgery that redirected bile acids to the latter part of the small intestine without altering the stomach.

Significantly, the team noted that this surgery also lowered primary bile acid levels in the bloodstream and decreased the size and spread of colorectal tumors as effectively as gastric bypass surgery. This was supported by an additional experiment, where they identified that primary bile acids promote the growth of colorectal cancer cells in laboratory settings.

The results indicate that focusing on primary bile acids may hold promise for cancer treatment. “We might be able to leverage various oral medications designed to reduce these bile acids to replicate some of the advantageous effects of gastric bypass surgery,” notes Vance Albaf from Louisiana State University.