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New UGA study demonstrates bacterial pathogens use hydrogen as energy source in animals
by Kim Carlyle
of University of Georgia
A new study, just published in the journal Science, shows for the first time that some bacteria that cause diseases in humans use molecular hydrogen as an energy source. The research could point the way toward new treatment regimens for everything from ulcers and chronic gastritis to stomach cancer.
Microbiologists at the University of Georgia worked specifically in mice with the gastric bacterium Helicobacter pylori, a pathogen that colonizes the mucosal surfaces of the human stomach and gives rise to gastritis, peptic ulcers and sometimes certain types of gastric cancer.
"This was completely unexpected, because most scientists have thought that hydrogen was always lost from the body as a waste product," said Rob Maier, Georgia Research Alliance Eminent Scholar and Ramsey Professor of Microbiology at UGA. "This is the first evidence that hydrogen remains in the body at substantial levels and is an energy source for pathogenic bacteria. Our knowledge that human pathogens can grow on hydrogen while residing in an animal may have profound implications for the treatment of some diseases."
Coauthor for the paper is Jonathan Olson, now an assistant professor of microbiology at North Carolina State University, who contributed to the work as a postdoctoral associate in Maier's laboratory at UGA.
Perhaps as important as the discovery that hydrogen can fuel the growth of Helicobacter is Maier's belief that the same process may provide energy for other human pathogens, such as Salmonella, E. coli and Campylobacter jejuni, the leading cause of bacterial human diarrhea illnesses in the world. These bacteria also have the hydrogen-utilizing enzyme, but the role of the enzyme has not yet been addressed, said Maier. Because the hydrogen comes from flora in the colon, something as simple as a diet change could profoundly impact the progress of disease from all of these bacteria.
Bacterial oxidation of molecular hydrogen is common in nature, but the presence and role of hydrogen in animals has been little studied. Tests have shown the presence of hydrogen in the breath of human test subjects, indicating it is somewhere in the body, but science was virtually unanimous in believing that whatever molecular hydrogen was produced in the body was excreted as an unneeded waste product, with no role in metabolism or cell growth. Maier resolved to find out once and for all where such hydrogen might be, so he inserted a tiny probe into the stomachs of living mice and measured the amounts of hydrogen in the area of the animals' mucosal layer.
The result was startling. After more than 30 measurements, Maier and Olson found large amounts of hydrogen present -- the first time that hydrogen has ever been detected in any vertebrate animal tissue. The team repeated the experiment on different stomach regions of more live, anesthetized mice and found hydrogen present in every sample, though in differing concentrations.
"We not only found this hydrogen present in the gastric mucosa of mice but we discovered that its use greatly increased the stomach colonization ability of H. pylori," said Maier.
The implications of the research reach beyond science to medicine for both humans and animals. An estimated 50 percent of humans, for example, are infected with H. pylori -- hundreds of millions of people -- though most show no symptoms from the pathogen. The bacterium is very good at coexisting with its host most of the time, but it causes a range of illnesses for which people spend vast sums each year seeking relief. No one knows how the pathogen is spread, and whether it is through food or water or physical contact remains speculative. Nor do scientists yet know how the hydrogen gets from the producers (the bacterial flora in the colon) to the hydrogen consumers at the walls of the stomach, though it could be through the bloodstream.
What is clear is that molecular hydrogen is apparently a virulence factor for human pathogens -- something entirely unsuspected before this research. (Hydrogen levels have recently been measured in the termite hind-gut and in the cockroach mid-gut, but this is the first evidence of it within vertebrate tissue. Mouse models are frequently used to unravel human health problems, since both share many of the same biological processes.)
"This really represents a new factor in understanding how a human pathogen grows and persists in an animal host," said Maier. "Hydrogen may play an especially important role in setting up the stable infection required for the most serious of the pathologies associated with H. pylori infection, gastric ulceration and cancer. This is because one hallmark of the pathogen is its persistence in the mucosa, and its long-term survival would be affected by the availability of its energy source, namely hydrogen."
The research may well open numerous avenues for new studies. It has been estimated that 14 percent of all the intestinal-produced hydrogen is excreted through the breath of humans, and Maier and Olson speculate that hydrogen may be carried to the lungs via the bloodstream. Though unstudied, it's possible that this hydrogen could serve as an energy source for pathogens in other areas of the body, including the lungs and internal organs.
Since the amount of hydrogen produced in the colon varies based on diet, and since the researchers have shown that H. pylori uses this hydrogen as an energy source, something as simple as a diet change could affect virulence and persistence of this and other pathogens.
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