Butyrate may have beneficial effects in reducing polyp initiation in individuals with familial adenomatous polyposis (FAP), according to an Australian study known as AusFAP. Finlay Macrae, MD, head of colorectal medicine and genetics at The Royal Melbourne Hospital is presenting the results of the study during Digestive Disease Week® (DDW) 2024.

“These data reinforce the notion that dietary interventions that increase resistant starch may reduce polyp initiation in FAP,” says Dr. Macrae. “It also supports the broader view that fiber is protective against bowel cancer and polyps.”

Many in vitro and preclinical studies have suggested that butyrate may play a role in colorectal cancer prevention and gut health, but applying these findings clinically has been difficult because it is not easy to deliver high quantities of butyrate to the colon, Dr. Macrae says. Butyrate itself is not very palatable and is readily absorbed in the small bowel.

To address these difficulties, Dr. Macrae’s group used a chemically modified form of resistant starch shown to lead to high levels of fecal butyrate. The starch, dubbed butyrylated high amylose maize starch (HAMSB), contains a halo of butyrate that is released by bacteria in the colon.

AusFAP was a randomized, placebo-controlled study of 72 individuals with FAP — a genetic disorder characterized by multiple benign polyps in the colon and an increased risk of colon cancer. Participants ingested either HAMSB or a low-amylose starch for six months. Participants in the HAMSB group then ingested the low-amylose starch for six months and vice versa. All participants were then followed for an additional six months with no intervention.

The researchers tested the impact of HAMSB on the number and size of existing polyps across the colon as well as the growth of new polyps in an area of the colon that had been cleared of polyps at baseline.

Key results from the per-protocol analysis include:

• HAMSB reduced the number of all polyps across the colon by 13%, especially small polyps (21%).
• In the area cleared of polyps at baseline, HAMSB reduced polyp initiation by 21% , especially small polyps (27%).
• There were too few larger polyps to independently assess the impact of HAMSB on their formation.

Although the results did not reach statistical significance, Dr. Macrae said, all the observations were consistent with a protective effect for HAMSB.

Dr. Macrae notes that while the effect on polyp initiation was modest, he believes it is clinically important. “If you can reduce polyp growth with a dietary intervention that is relatively affordable, that can really mean something to patients.”

Dr. Macrae notes the difficulty in assessing polyp counts as an endpoint. Doing so requires reviewing hundreds of colonoscopy videos, segment by segment. He hopes that new technologies will make it easier to objectively quantify polyp burden.

He also stresses that while the trial has some promising results, clinicians should not change how they approach preventive measures for colon cancer, particularly in those with FAP.

“You still need to manage patients with FAP in the same way,” he says. “Endoscopic interventions and surgery when required are still the standard of care for managing these patients. We should not rely on dietary interventions alone.”

Dr. Macrae hopes that future trials can continue to shed light on HAMSB as a cancer preventive and help to commercialize the product to make it more widely available.

Dr. Macrae’s oral presentation, “Can butyrate prevent colon cancer? The Ausfap study: A randomised, cross-over clinical trial” on Monday, May 20, at 8:15 a.m. EDT is part of the AGA Clinical Science Plenary.