More than 60 million Americans suffer from heartburn at least once a month, and another 15 million – every day. If you are among them, you have a big company. Remember the hoarse voice of bill Clinton from the White house? He suffered heartburn. So was George W. Bush if he drank coffee or ate mints. Star quarterbacks Brett Favre and John Elway played with the same problem in American football. Great baseball players Jim Palmer and Nick Markakis came out on the court with her. When singers have problems with their voice, a common cause is discomfort in the esophagus. What is this part of the body that causes suffering to so many people?
The esophagus is a tube about twenty centimeters long, connecting the pharynx with the stomach. As in the stomach, the walls are lined with mucus, which helps the food slip down. Every time you chew another piece, the muscle ligament at the top of the esophagus opens and you swallow the contents. Swallow your saliva and feel how they work.
Another group of muscles is located at the bottom of the esophagus and controls the exit to the stomach. When food accumulates, this sphincter opens and the food falls further. If the esophagus is empty, it closes. Thus, the food enters the stomach in ordered portions, as if on a one-way street. Swallowing movement is controlled by conscious efforts, but the opening and closing – no. When the esophagus works well and you don’t eat, the “passage” remains closed; gastric juice and contents can’t go back. But if it does not close completely, heartburn begins. The acid goes up the tube, causing a burning sensation.
Heartburn comes and goes and by itself is not a particularly serious problem. Just wait it out or take a couple of antacid pills and you’ll be fine. But when the phenomenon becomes chronic, you risk getting GERD, or gastroesophageal reflux disease: it is very unpleasant and can cause heartburn every day. In addition, sometimes nausea, belching, difficulty swallowing and chest pain are manifested. The esophagus is irritated, and eventually, scars may appear on it. Now it is one of the most common diseases in developed countries: it affects 10-20% of American adults.
One of the hints that pylori can play a role in esophageal diseases came from a totally unexpected side. As you remember, in 1987, Guillermo Perez-Perez and I developed a blood test for this bacterium, and I was positive, although there were no symptoms. A few years later, we used blood serum to recognize a protein produced by a particularly virulent group of strains of H. pylori, which are most common in people with peptic ulcer disease. In 1993, it was discovered that this protein, CagA, was also involved in the development of gastric cancer.
My father had an ulcer. My mother is from Eastern Europe, where the incidence of stomach cancer is high. Am I at risk of getting sick myself, given my family history? I feel great, although I had a strain of H. pylori, which is most closely related to gastric ulcer. But obviously, if I believed the results of my own research, I had to take an antibiotic, destroy the bacteria and see what would happen. Why risk a terrible disease if it can be prevented?
It is time for teamwork. I asked a colleague of Richard Pick’s who had just completed his postgraduate gastroenterology course to do an endoscopy for me. He had to insert a tube into my nose that goes through my throat and esophagus into my stomach. Inserting and removing it, he had to follow the process. Through it, the medic was pushing a small, scissors-like device with which he took a biopsy of the stomach.
Another colleague, John Atherton who came to us from England, had to handle the samples and to highlight my strain of H. pylori in the Petri dish. After Guillermo Perez-Perez again had to take a blood test for the level of antibodies. Then I had to drink a course of antibiotics to kill the bacteria and see if the level of antibodies would decrease over time.
I had no idea how uncomfortable the procedure would be. On the day of the biopsy, Rick gave me medicine to relax and remember almost nothing afterwards. It worked, except for one thing: each of seventeen times, when I inserted an endoscope into the stomach, I choked. Why do so many biopsies? We are researchers: if you have already agreed, why not get more material for future research.
After I was told that in a stomach there is no ulcer, nor any other “abnormalities”. I expected it, but it was still good news. John Atherton made seeding three samples of the bacteria in Petri dishes and waited for growth. I took antibiotics for ten days.
To my surprise, nothing grew. In the bacterial samples did not appear any of the colonies of H. pylori. Blood tests showed I was a carrier, but where did they go? We assumed that there were relatively few of them in the body, despite the high levels of antibodies in the blood test. Or maybe a high level of antibodies inhibited the action of the bacterium, but did not destroy it-just like an oyster covers a pearl grain of sand, from which a pearl is obtained. Not being able to get rid of the sand, the body makes it less annoying.
Over the next year, we were constantly doing blood tests and Guillermo discovered that my level of antibodies to H. pylori gradually (and significantly) decreased, as it should have happened after successful antibiotic therapy. I could breathe easy. The risk of stomach cancer has dropped to almost zero.
Then something strange happened. Six months after the destruction of bacteria after eating and in the evenings began heartburn – before it was never. I was wondering if it had anything to do with antibiotics. At medical conferences, I heard the stories of doctors that among the side effects when taking drugs this happens, but seriously this topic has not been studied.
Unfortunately, gastroesophageal reflux disease, if left untreated, causes much more serious problems. It can lead to a tissue injury called Barrett’s esophagus, which in turn can develop into adenocarcinoma, a form of cancer. In the past, almost all esophageal cancers developed from malignant changes in the upper and middle part of the esophagus, closer to the mouth, and it was a different type of cancer. But since its discovery in the 50s, Barrett’s disease has sometimes developed into adenocarcinoma either in the lower esophagus or in the upper stomach. Once it was a rarity, amounting to only 5% of all cases of such diseases in the United States. But now the percentage is growing faster-over the past thirty years has become six times more. Now adenocarcinoma is more than 80 % of all new cases of esophageal cancer in the United States.
Then we did not have this statistics.
Despite many theories, no one knew why the incidence of all these related diseases is increasing at the same time: the GERD, the most mild and common form, was discovered in the 30-ies, Barrett’s esophagus, a more advanced and less common stage in the 50s, and frightening many adenocarcinoma – in the 70s. They are clearly linked.
By that time, we had mostly studied how pylori damages the stomach. Rick Peak, the doctor who did my endoscopy, investigated the differences between the effects on the stomach of CagA-positive (most virulent) and CagA-negative (less virulent) strains. Since the bacterium was then associated with a wide variety of diseases, I asked him to investigate its relationship with GERD. With the help of a blood test, we could determine whether GERD is more common in patients with H. pylori than in others. Working with colleagues from the Cleveland clinic, specialists in reflux disease, he collected a collection of blood serum samples. And Guillermo conducted blind tests: he didn’t know what samples are taken from healthy people, and what – at the sick.
Surprisingly, instead of a direct connection between the presence of H. pylori and heartburn, Rick discovered the inverse proportionality. Without bacteria GERD developed twice as often. And then it turned out that the chances are higher not even two, but eight times. How can this be explained?
I asked Rick about the Association of the disease with the CagA protein, since we knew the strains were more virulent. He said that the relationship is even stronger and also the opposite: the smaller the Cag, the more GERD. The results were the exact opposite of what was expected.
I really knew little about GERD, so I asked Rick whether the rising incidence. After a positive response, our work on pylori went in a new direction.
That first study was the basis for the hypothesis that the bacterium protects against GERD. The inverse proportionality was quite noticeable. But what did it mean? How can a microbe living in the stomach and associated with ulcer and cancer protect the esophagus? Or, perhaps, a disease of the esophagus destroy it?
For many years, a group of German doctors treated patients with duodenal ulcer with antibiotics to remove pylori. Then they began to study the effects of treatment-three years after therapy, examined the stomach and esophagus of each patient. About half of them didn’t have any more pylori. In the first years after the development of antibiotic therapy, such results were not uncommon. Now doctors prescribe other courses that are much more likely to work successfully-in 80 % of cases.
Comparing the two groups after therapy, German scientists found that patients with pylori had heartburn in 12.9 %. And those who were left without it-almost 26 %. The destruction of the bacteria resulted in a more than twofold growth of the oesophagus. The result showed in what direction is the causal relationship: therapy worsened the condition of the esophagus, contributing to the development of heartburn.
Many criticized the article, finding a lot of technical quibbles, and during the year at medical conferences it was very fashionable to condemn it. But my attention was drawn to it. I knew that the head of the group, Joachim Labenz, was a serious, honest scientist.
Over the next few years, my team conducted additional research with colleagues around the world and found exactly the same dynamics: the inverse proportion between the presence of H. pylori and the incidence of GERD, Barrett’s esophagus and adenocarcinoma. People with the most virulent garden-positive strains that are associated with gastric ulcer and cancer, were most protected from diseases of the esophagus.
It looked very mysterious. As a bacterium of the villain can protect the esophagus? And the most virulent strains are also the most effective.
Answers can be found in gastric juice. Acid kills most bacteria. But over the millennia of evolution, pylori has learned to avoid death. In a sense, she even likes a sour environment: there are, of course, certain difficulties associated with life in such a hostile environment, but there are no competitors. As you know, the enemy of my enemy is my friend.
In fact, a considerable number of studies from different laboratories, including my own, have shown that H. pylori helps regulate stomach acidity. They cause inflammation that affects gastric hormones. And those, in turn, turn on or off the production of acid.
In the first decades of life, this balancing system works very well. Under the microscope, the glands that produce gastric juice resemble leaves swaying in the wind. But with age from chronic inflammation, the walls of the stomach wear out, and those who have pylori-faster. Glands are shortened and flattened. When this happens, the so – called atrophic gastritis develops-the stomach produces less acid. As a result, the ulcer passes. Schwartz’s law,” no acid, no ulcer, ” holds.
But the people who have H. pylori either never had, or taken out by antibiotics, a high level of acidity is retained even after forty years. Thus, perhaps for the first time in all historical and prehistoric times, many people live to middle age with intact glands to produce acid. They have stomach contents rising up the esophagus, very acidic, higher levels of digestive enzymes – and it causes more damage. And since H. pylori is now much less common at an early age, most modern children grow up with a different system of acidity regulation than in previous generations – the bacterium is no longer involved in physiological processes. Heartburn in children, once incredibly rare, is now more common, and many are treated with drugs that reduce the acidity of the stomach. Could one be related to another?
We found that, in fact, the double – edged sword of the pathogen, the risk of ulcers increases with age, and then of stomach cancer; it is beneficial to the esophagus. The bacterium protects against GERD and its consequences, including other types of cancer. With the disappearance of pylori, the number of cases of gastric cancer decreases, but the incidence of adenocarcinoma of the esophagus increases. This is a classic case of amphibious. The facts.