FOR IMMEDIATE RELEASE
January 29, 1998
CONTACT: Christine Shtogren
(804) 828-6604
E-mail: shtogren@HSC.vcu.edu
http://www.vcu.edu/exrel/news/

VCU RESEARCHERS LINK GALLSTONES TO INTESTINAL BACTERIA

RICHMOND, Va. — For some people, it is a freight train of pain, blasting from the abdomen through the upper half of the body, stopping them in their tracks. For others, it is a gnawing ache, migrating upward through the torso.

Any of the one million people diagnosed with gallstones annually knows the pain can last for hours. Half of them opt for surgery, ringing up a $5-billion tab each year.

Gallstones typically are associated with high-fat diets, rapid weight loss and women’s hormones, but researchers at Virginia Commonwealth University are homing in on another possible culprit — two rod-shaped bacteria in the gut.

Leading one of the few research efforts of its kind worldwide, VCU scientists are collaborating with colleagues at Guy’s and St. Thomas’s Medical School in London and the University of Munich to study the bacteria-gallstone connection. At the same time they are working to develop a drug that eliminates these bacteria and prevents the formation of gallstones.

The scientists believe the tiny bacteria called clostridium and eubacterium set off a biochemical chain reaction, ultimately leading to an increased risk for gallstones — the pea-sized lumps of hardened cholesterol that can cause so much pain.

The on-going gallstone study is funded by a $5.15 million National Institutes of Health grant, which supports VCU’s broad-scale research on bile acids and cholesterol metabolism. "These bacteria convert cholic acid, a ‘good’ bile acid made by the liver into harmful deoxycholic acid," said Phillip Hylemon, Ph.D., principal investigator of the study and a microbiologist at VCU’s Medical College of Virginia Campus. "Deoxycholic acid causes the liver to secrete cholesterol-supersaturated bile — a key risk factor for developing gallstones."

The data that Hylemon and colleagues are collecting suggest a bacteria-gallstone link. "From both London and Munich, our study findings are consistent -- gallstone patients had high levels of the intestinal bacteria that generates deoxycholic acid, whereas non-gallstone patients had low levels," explained Hylemon.

In fact, when the two groups were compared, gallstone patients had 100 to 1,000-fold higher levels of bacteria than the control group.

Hylemon and his colleagues found that after gallstone patients were treated with antibiotics, their deoxycholic acid levels and cholesterol-supersaturated bile dropped below the threshold required to develop gallstones. But broad-scale antibiotics tend to wipe out both bad and good bacteria in the colon.

So Hylemon is working with the German pharmaceutical firm Hoechst Marion Roussel to develop a drug that specifically targets and eliminates the destructive bile acid and blocks the pathway leading to the production of the cholesterol-supersaturated bile.

Beyond gallstones, scientific evidence is mounting that deoxycholic acid may play a role in colon cancer as well. While Hylemon admits further research is necessary, his research findings, published in the December 1997 issue of the Journal of Lipid Research, show how deoxycholic acid activates cancer-promoting activity in cells. "The bottom line is people with colon cancer also seem to make more potentially damaging deoxycholic acid."

Decreasing chances for colon cancer and preventing gallstones may be as simple as eating a low fat diet. "It appears that a high fat diet causes these bacteria to proliferate in the first place," explained Hylemon. "People who eat high fat diets have about 1000-fold higher levels of these bacteria than those who consume low fat diets."

"Deoxycholic acid is implicated in cholesterol gallstone disease and colon cancer," concluded Hylemon. "A more detailed understanding of how deoxycholic acid is formed may lead to improved approaches in preventing and treating these major diseases."

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