By: Paula Rausch
Dietary supplementation with a beneficial bacterium that plays a key role in breaking down a substance linked to kidney stone formation could someday prevent stone disease in people, a University of Florida researcher and his colleagues have discovered.
Giving rats high doses of a naturally occurring intestinal bacterium called Oxalobacter formigenes safely lowers chronically high levels of oxalate - a byproduct of digestion that is a major cause of kidney stones - to near normal, the scientists reported in the October issue of The Journal of Urology.
Scientists at UF and other institutions previously linked kidney stone formation to a lack of O. formigenes in the body, but the article provides the first published evidence that supplementation with the bacteria may help prevent stone formation. The research was conducted in collaboration with scientists at Ixion Biotechnology, a UF technology licensee located in Alachua, Fla.
UF and Ixion researchers are now developing the bacterium as a treatment for kidney stone disease in people. They are in the process of seeking approval from the U.S. Food and Drug Administration to begin testing in humans a frozen form of the bacterium that would be mixed with a beverage and consumed. The National Institutes of Health has awarded Ixion a small business grant of $786,000 over the next two years to develop the bacterium into pill form.
"Outside of attempts to change people's dietary habits, which are not very successful on a long-term basis, there has been a lack of successful treatment for lowering oxalate levels," said Dr. Ammon B. Peck, a professor of pathology, immunology and laboratory medicine at UF's College of Medicine.
"This particular treatment is such a simple process, and if its safety and efficacy holds up in humans, it certainly will be a major step forward for individuals suffering from this disease. We're very optimistic that this will be something that we can bring to the public fairly soon," said Peck, who also is the chief scientist at Ixion, where the research was conducted.
Kidney stone disease is a painful and costly disorder that afflicts about 5 percent to 10 percent of people worldwide. More than three-quarters of stones form because of excessive oxalate, which binds with calcium to form crystals that become stones. Oxalate is found in high concentrations in many foods, including asparagus, tea, broccoli, peanut butter, spinach and chocolate. The disease is more common in men and in certain geographic regions. About $2.5 billion is spent annually treating it, including surgically removing stones or repeatedly aiming high-energy sound waves at them until they disintegrate - therapies that can damage the kidneys.
O. formigenes could be the newest member of a class of beneficial bacteria called medical probiotics, used to treat a variety of conditions. Currently, the most common is Lactobacillus, which is found in active-culture yogurt and other supplements and has been shown to prevent or treat diarrhea.
For the current study, supported by a $26,000 grant from the Ross Products Division of Abbott Laboratories, 26 rats received high doses of oxalate, predisposing them to kidney stone formation. Using cultures of O. formigenes grown from a sample originally obtained from a wild rat, researchers gave groups of the study animals four different doses of the bacterium through a feeding tube during a two-week period. A control group was fed a normal diet and did not receive the bacterial supplement.
Within two days of starting the supplementation, urinary levels of oxalate declined in rats fed the high-oxalate diet. The higher the dose of the bacterium the rats received, the less oxalate excreted through the kidneys. In animals receiving the highest doses of O. formigenes, the amount of oxalate present in the urine dropped to the levels found in the control group.
During the treatment period and for four weeks afterward, all the rats remained healthy and showed no adverse effects.
First discovered in sheep in the mid-1980s by co-researcher Milton J. Allison, a University of Iowa microbiologist, O. formigenes is a useful bacterium that people pick up from the environment from about 1 to 3 years of age. It is present in the intestinal tracts of almost every animal species UF researchers have tested, but is susceptible to antibiotics, dietary changes, health conditions and unknown environmental factors.
"People who get stones more than once are more likely to keep getting them, and we have found that people who make a lot of stones lack the O. formigenes bacteria necessary to degrade oxalate from the body in order to prevent kidney stone disease," said Harmeet Sidhu, vice president and director of research for Ixion's oxalate division, and the paper's principal author. Prior to joining Ixion, Sidhu was a visiting scientist at UF.
"Because this bacterium is something that nature has provided, it can be a good way of
preventing absorption of oxalate from the diet. And the most important thing is that this
treatment proved very safe. It did not have any toxic effects, even in laboratory rats that did not
have the bacteria normally and had never been exposed to it before," she said.
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