CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 335-8034
Release: Oct. 10, 2000
UI researchers find that a simple sugar may prevent lung infections in
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, reports 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
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
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
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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