"People thought that the esophagus wasn't hospitable to bacteria," says Martin J. Blaser, M.D., Frederick King Professor and Chairman of the Department of Medicine, and Professor of Microbiology, an author of the study. Bacteria were believed to move through the esophagus, the tube connecting the mouth to the stomach, as food-borne passengers on route to the stomach.
But the new study in the March 23 print issue of the Proceedings of the National Academy of Sciences demonstrates that bacteria do indeed live in the esophagus, and these microbes are a diverse bunch. "This study provides evidence for the first time that there are indigenous microbes in the human esophagus," says Zhiheng Pei, M.D., Ph.D., Assistant Professor of Pathology and Medicine, the study's lead author.
The findings may have profound implications for treating diseases of the esophagus, including gastroesophageal reflux disease (GERD), which afflicts some 10 million people in the United States. Chronic inflammation associated with GERD can lead to the development of a precancerous condition called Barrett's esophagus. If disease-causing bacteria are ever found in the esophagus, it may one day be possible to treat these diseases with antibiotics.
While bacteria in the esophagus will be news to most people, the NYU researchers had suspected that the food tube harbored microorganisms. After all, bacteria have now been found in deep-sea vents, hot springs, volcanoes, and other extremely harsh environments. "By comparison, the esophagus seemed much more hospitable," says Dr. Blaser.
In human biology, too, there have been surprises concerning bacteria. For many years, doctors didn't believe that bacteria could survive in the acid environment of the stomach. But in the early 1980s, researchers discovered that the bacterium Helicobacter pylori lived in the stomach and is associated with ulcers. Antibiotics are now routinely used to treat ulcers. In subsequent years, Dr. Blaser and other scientists established the bacterium's link to certain kinds of stomach cancers.
The connection between H. pylori and gastric cancer was one of the reasons why the NYU researchers were drawn to the esophagus. Might certain kinds of disease-causing bacteria also reside in the esophagus? While bacteria have long been known to inhabit the mouth, the evidence that bacteria even lived in the esophagus was inconclusive. Previous studies of the esophagus didn't consistently find bacteria in the esophagus that could be cultured. Textbooks have never described microbes in the esophagus.
Rather than relying on the conventional methods of culturing bacteria in petri dishes in the laboratory, the researchers decided to mine DNA libraries that have been compiled of bacterial genes. They used a technique called PCR (polymerase chain reaction) to greatly amplify snippets of DNA extracted from biopsies of tissue from the esophagus, and they compared the sequences of the DNA in the biopsies to known bacterial DNA.
The biopsies were taken from four patients who each had a healthy esophagus. Specifically, the biopsies were taken from the distal esophagus, the part closest to the stomach. This area is especially vulnerable to injury due to the backwash of gastric contents that occurs as a consequence of GERD.
The researchers found 95 species of bacteria, and they estimated that they were able to sample 56 to 79 percent of the species in the biopsies. Therefore, even more species may be present. Many of these bacteria resemble garden-variety microorganisms that aren't known to cause disease.
More than 60 percent of the esophageal bacteria were shared among all four individuals, indicating that populations of certain bacterial species appear to be common to all people, according to the study. Although many of the bacteria in the esophagus were highly related to the bacteria found in the mouth, certain bacteria were not known residents of the mouth, says Dr. Pei. This finding suggests that some, if not all, "esophageal bacteria may be unique," he notes.
Importantly, Dr. Pei also directly viewed bacteria colonizing the surface of the esophagus, proving that the bacteria weren't simply traveling through the tube but had taken up residence in the tissue lining it.
Esophageal adenocarcinoma, a kind of cancer, has been increasing rapidly in white men, according to the National Cancer Institute, which sponsored the NYU study. "Animal studies suggest that inflammation and normal bacteria work in concert to cause colon cancer," says Dr. Pei. "Esophageal cancer arises in an area of the esophagus where chronic inflammation is occurring," notes Dr. Pei.
In the next phase of their work, the researchers plan to identify the bacteria in the esophagus in people who have GERD and other esophageal conditions. They suspect that they may find different bacteria in the samples of unhealthy esophageal tissue, which could suggest that microorganisms are playing a role.
"We are operating in the framework of the 'microbiome', a term coined by Nobel Laureate Joshua Lederberg," says Dr. Blaser. "It means that microbes are part of us, part of our identity. They aren't just passengers," he says, " but are, in essence, metabolic and physiologic compartments of the human body."