Oct. 13, 2000 IOWA CITY, Iowa - The lungs contain substances that kill inhaled and aspirated bacteria, thereby preventing lung infections. This system may be disrupted in people with cystic fibrosis (CF). University of Iowa researchers have discovered that a simple sugar may enhance the natural defense system and potentially help delay or prevent the onset of deadly bacterial infections in CF lungs. CF is the most common fatal inherited disease in Caucasians of Northern European descent and has no cure.
The UI team, led by Joseph Zabner, M.D., associate professor of internal medicine, report in the October 10 issue of the journal, Proceedings of the National Academy of Sciences that a sugar, xylitol, lowers the salt concentration of the liquid that covers cells lining the inside of the lungs, thereby enhancing the bacteria-killing activity of the body's natural antibiotics.
Normal lungs have an effective innate defense system to counteract the small numbers of airborne bacteria we constantly inhale. These organisms land in the thin layer of liquid, called airway surface liquid, that overlays the cells lining the inside of the lungs. The airway cells produce a host of natural antibiotic substances and secrete them into the airway surface liquid where they kill the invading bacteria. However, in the lungs of people with CF the system breaks down, allowing the bacteria to get a foothold and eventually develop into the chronic infections that are the leading cause of death in CF patients.
UI scientists have suggested that the natural defense system in CF patients is disrupted because a genetic defect results in an increase in the salt concentration of the airway surface liquid.
"We have previously shown that the natural antibiotics work best in low salt and that the salt concentration in the airway surface liquid in cell models of CF lungs is high," Zabner said. "We thought that if we could lower the salt concentration in the liquid, it might be a way to prevent the onset of infection in the lungs of people with CF."
Zabner and his colleagues knew that they needed a substance called an osmolyte that would not be easily absorbed by the cells and would lower the salt concentration to favor the antimicrobial agents. Simple sugars fit the bill. However, airway bacteria can use many sugars as an energy source to aid their growth.
"As we were testing the sugars I read about some research showing that chewing gum containing a sugar called xylitol seemed to prevent inner ear infections," Zabner said. "This information and the fact that xylitol has been used for years in Europe as a safe sugar substitute, made me think that xylitol might be a good choice for our studies."
The UI team used a series of experiments to prove that xylitol was not used by airway bacteria to grow, and that the sugar did lower the salt concentration of the airway surface liquid, thereby enhancing the bacteria-killing activity of the natural antibiotics.
The UI team then used human volunteers to test the principle that xylitol helps the body to fight against airborne bacteria.
The amount of a particular bacterium, commonly found in nasal passages, was assessed for 21 healthy volunteers. In a blinded, randomized test, the volunteers then sprayed either a xylitol or a salt solution into their nostrils four times a day for four days. After that time, the nose-bacteria level was retested. The volunteers then waited a week to allow their nose bacteria levels to get back to normal and repeated the spraying experiment with the other solution.
Cells lining the nasal passages are almost identical to cells that line passages in the lungs, although the environment is very different. Normal subjects have fairly constant levels of bacteria in their nostrils. These factors, and the ease of testing changes in bacterial levels in nostrils, made the nose a good place to show that the sugar could do something in the body.
The results showed that the sugar spray significantly reduced the number of the nasal bacteria. The saline solution did not significantly alter the amounts of bacteria.
Zabner said the UI researchers plan to test whether the sugar can be effective in preventing bacterial infection in the lungs of people who are prone to infections such as pneumonia.
"The hope is that this could help prevent, or at least delay, the onset of infection in lungs of people with CF and people who don't have CF but are also prone to lung infections," said Michael J. Welsh, M.D., a Howard Hughes Medical Institute (HHMI) investigator and Roy J. Carver Professor of Internal Medicine and Physiology and Biophysics at the UI, who worked with Zabner on this study.
In addition to Zabner and Welsh, the other UI investigators on the study included Michael P. Seiler, research assistant in internal medicine, Janice L. Launspach, R.N., HHMI research associate in internal medicine, Philip H. Karp, HHMI research associate in internal medicine, William R. Kearney, Ph.D., associate research scientist and director of the Nuclear Magnetic Resonance Facility, and Jeffrey J. Smith, M.D., associate professor (clinical) of pediatrics. Dwight C. Look, M.D., assistant professor of medicine at Washington University in St. Louis was also part of the research team.
The research was funded in part by grants from the National Institutes of Health and the Cystic Fibrosis Foundation.
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