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November 13, 2000
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Antibiotics, Yogurt Seen As Potential Treatment for Common Liver Disorder

—Hopkins scientists identify bacterial, intestinal links to fatty liver disorder

If mouse studies hold true for humans, a daily cup of yogurt or dose of antibiotics may become the first effective treatments for a common and sometimes fatal obesity-related liver disorder, Hopkins scientists report.

Specifically, the scientists discovered what they believe is the first evidence that fatty liver disease (FLD) may be caused by an overactive inner "distillery" in the obese that produces excessive amounts of alcohol. "Obesity-related FLD is already a serious public health problem in industrialized nations and will most likely become more prevalent as the epidemic of obesity continues," says Anna Mae Diehl, M.D., a professor of medicine at Johns Hopkins and principal investigator of the study.

Reporting in the November issue of Gastroenterology, the scientists describe a study in obese and lean mice in which they found that obesity contributes to digestive system malfunctions that in turn allow normally harmless, but always present, gut bacteria to ferment undigested food, producing alcohol that might ultimately damage the liver.

"Our study suggests that obese mice with fatty liver disease make too much of their own alcohol, mimicking what we see in fatty liver disease produced in humans who drink alcohol to excess," says Diehl.

"Whenever the bowel fails to move normally, the partially digested food material becomes a food source for the intestinal bacteria. These bacteria overgrow, ferment the food and produce alcohol," adds Diehl. "If what we see in mice turns out to be true in people, treatment and prevention of obesity-related FLD could be relatively easy using yogurt or oral antibiotics to constrain intestinal bacterial overgrowth."

Both humans and animals have bacteria in their intestines that can ferment dietary carbohydrates to make alcohol. Thus, in a sense, we have our own little internal stills. In situations in which partially digested food sits in the intestine for long periods of time, bacterial overgrowth occurs, leading to more alcohol production in the intestine.

Food might stay longer in the intestinal tract of obese people, say researchers, because they are known as a group to have higher rates of disordered bowel motility, including irritable bowel syndrome. Obese mice have also been shown to have problems with intestinal motility as they age. "We think that obesity changes the normal functioning of the intestines, including the way in which they propel their contents from one end to the other," says Diehl. "As a result, there are static periods during which ethanol (a form of alcohol) is overproduced."

Almost a fourth of adults in many industrialized countries suffer from excessive fat accumulation in the liver, with obesity being the number one risk factor. Once fatty liver disease develops and becomes chronic, current treatments are limited and about 10 percent of obese patients with cirrhosis due to non-alcoholic FLD die of liver-related causes in every 10 year period.

Because tissue samples from patients with obesity-related FLD and alcohol-related FLD look the same under the microscope, Diehl and her colleagues wondered whether obesity alone might somehow increase exposure of the liver to alcohol.

To investigate the idea, the researchers fed an alcohol-free diet to mice with a genetic form of obesity and also to normal, lean mice for 24 weeks. They then sampled their breath (for the breakdown products of alcohol, much the way a Breathalyzer test for blood alcohol levels works) and examined their livers. In a related experiment, they studied obese and lean mice for age-related differences in alcohol production. The researchers found that all of the obese mice had fatty livers and, when they aged, they produced roughly five times more ethanol than their lean counterparts.

In a third experiment, Diehl and her colleagues significantly reduced the amount of alcohol produced in obese mice by giving them oral antibiotics to kill some of the intestinal bacteria.

"There is a possibility that we may be able to ask obese patients to eat a daily cup of yogurt, which has been shown to have an antibacterial effect, or take an oral antibiotic every day to minimize their chances of getting fatty liver," Diehl said. "Of course, yogurt would be easier and less expensive than antibiotics."

To learn more about gastrointestinal disorders, visit http://www.hopkins-gi.org. Other authors of the study include Keary Cope and Terence Risby from Johns Hopkins. The study was funded by the United States Air Force Office of Scientific Research.


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