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Gut reaction to the cholesterol count

A bacterium introduced into the intestine could help to reduce heart disease, says Bernard Dixon

Could a microbe be introduced into the body to lower the amount of cholesterol circulating in the bloodstream, and thus prevent or ameliorate coronary heart disease?The idea is strongly supported by research at Iowa State University in Ames, Iowa, where researchers have used a bacterium to reduce artificially raised cholesterol levels in rabbits. The treatment had no adverse effects on the animals, and the scientists believe that the same strategy could be of value in humans.

Cholesterol-lowering drugs are already available on the market, but, like most drugs, none are totally free of side-effects.A natural and harmless microbe that simply breaks down cholesterol in the body would be preferable to any type of synthetic drug.

The fact that raised cholesterol in the bloodstream promotes the development of atherosclerosis (narrowing of the arteries) is beyond question. Moreover, surveys worldwide have established that lowering the circulating cholesterol level diminishes the risk of a first heart attack and of subsequent attack in a person who has already suffered one. Some of these studies have shown that the danger of death from cardiovascular disease is also reduced.

Researchers atIowa State University aimed to introduce a microbe into the small intestine, to break down the cholesterol found in food and bile. The microbe would colonise the intestine, growing permanently alongside the many others that normally live there. The result would be to lessen the quantity of cholesterol absorbed from the small intestine into the bloodstream.

The researchers based their strategy on the isolation, several years ago, of bacteria capable of converting cholesterol to coprostanol, which is absorbed very poorly from the intestine. Unfortunately, most of these bacteria proved to be exceedingly difficult to culture in any quantity in the laboratory.

Last year, however, Donald Beitz and his colleagues in Ames announced that they had discovered a much more promising bacterium, which they called Eubacterium coprostanoligenes. They found it in pig manure (though it may originally have come from human faeces). The bacterium converted cholesterol into coprostanol and could be cultivated relatively easily at the laboratory bench. The researchers have given the bacterium to rabbits and found that it does indeed markedly reduce the level of circulating cholesterol.

Some microbes taken by mouth would be destroyed, or at least their numbers drastically diminished, by the highly acidic digestive juices in the stomach. The researchers first had to check this possibility. They found that Eu. coprostanoligenes could survive these conditions (simulated in a test-tube) for at least two hours and retain its ability to grow and attack cholesterol. Next they fed a diet rich in cholesterol (the human equivalent might be an excess of eggs or offal) to six New Zealand white rabbits each day for nearly two months. Predictably, this heightened the cholesterol level in their bloodstream. Three of the rabbits then received a culture of Eu. coprostanoligenes each day for 10 days, while the other three were given the same dose of the same bacterium after it had been killed by boiling.

As reported in this month's Letters in Applied Microbiology, administration of Eu. coprostanoligenes lowered considerably the quantity of cholesterol in the animals' bloodstream. From the end of the 10 days until the experiment was terminated over a month later, the rabbits that had received the living bacterium showed a reduction of more than a quarter in the cholesterol level as compared with those given the dead bacterium.

But was the microbe really having this effect by converting cholesterol into coprostanol, as the experimenters had hoped? They were able to confirm this explanation by examining the contents of the rabbits' digestive tracts and analysing them for both substances. As compared with the animals given the dead Eu. coprostanoligenes, those that had received the living bacterium showed much higher ratios of coprostanol to cholesterol. This showed that the bacterium, having colonised the rabbits' intestines, was indeed actively attacking cholesterol and turning it into coprostanol.

For people in many developed countries, coronary heart disease is a major killer, causing more deaths than all forms of cancer combined. Introducing the same bacterium to the human intestine could be particularly beneficial in individuals who have very high cholesterol levels not because of unwise eating habits but because they have the inherited condition called familial hypercholesterolaemia.

Donald Beitz is trying to improve the technique by varying factors such as the dose of Eu. coprostanoligenes and the period over which it is administered. Then, by courtesy of a food company which is trying to incorporate the bacterium into its yoghurt, they will see whether it works in humans. This could be the most health-giving yoghurt of all time.