stomach ulcer H pylori

Several months ago, I received an alarming phone call from my nephew: He had a horrible pain in his abdomen which caused him to double over. His stool was pitch black. It was obvious that he had an acute stomach ulcer, probably bleeding. What could cause this painful disease?

Since the late 19th century, doctors described the existence of bacteria in the stomach, but for a variety of reasons these reports did not gain traction or were simply not believed. The bacterium, later named Helicobacter pylori, was rediscovered in 1979 by Australian pathologist Robin Warren, who did further research on it with Barry Marshall beginning in 1981; they isolated the organisms from mucosal specimens from human stomachs and were the first to successfully culture them. In their original paper, Warren and Marshall contended that most stomach ulcers and gastritis were caused by infection by this bacterium and not by stress or spicy foods as had been assumed before. Their report was met with universal disbelief. I remember my own dismissive reaction when I read the first papers. An organism living in such an acidic environment (pH 2-3)? And not as a transient tenant, but a permanent resident? “Everybody” knew that stomach ulcer is caused by stress…there must be some mistake here.

The experiment that changed everybody’s mind was when Barry Marshall, in a dramatic effort to convince the medical world, swallowed a petri dish of H. pylori, showed with gastric biopsy that the bacteria indeed colonized his stomach, developed gastritis within weeks after swallowing it, eradicated it with a combination of bismuth subsalicylate (Pepto-Bismol) and metronidazole (Flagyl), and a second endoscopy 10 days later confirmed that the gastritis had resolved. It was only then, in 1994, that NIH (the National Institutes of Health) published an opinion stating that most recurrent gastric ulcers were caused by H. pylori, and recommended that antibiotics be included in the treatment regimen. In 2005, Warren and Marshall were awarded the Nobel Prize for their work.


What is H. pylori?

This bacterium is a wonderful example of biological adaptation. It burrows into the mucous layer (a gel-like mucus layer) of the stomach, and that’s where it stays. But to survive in this hostile environment, it had to somehow protect itself from the acid. Urea is normally secreted by the epithelial cells (these are the cells lining the stomach). The bacteria secrete an enzyme, urease, which breaks down urea to ammonia and CO2. Ammonia does a wonderful thing for these bacteria: It neutralizes the acid in the vicinity, thus allowing them to thrive in this forbidding environment. But it also does something else: It kills the epithelial cells that come in contact with it. Thus it, and some other proteins secreted by the bacterium, cause gastritis (inflammation of the stomach lining) and, eventually, an ulcer.


What about the acid?

We are not completely blameless. H. pylori gets some help from us in causing gastritis and ulcers. Once the mucus layer is damaged by bacterial colonization, the epithelial cells lie bare and defenseless against the destructive effects of the acid. This can explain the relationship between emotional upset and ulcer disease: Stress hormones cause an increased secretion of acid. Coffee has also been shown to increase acid secretion.  Unfortunately, decaffeinated coffee is not going to help; chemicals that cause an increase in acid secretion are present also in decaf. The same is true for excessive alcohol consumption; it damages the mucous layer and exposes the cells to acid. Add to that H. pylori, and you are in trouble.


Eradicate! eradicate?

H. pylori is an ancient organism that has lived in human stomachs probably since the beginning of our species, about 4 million years ago. It is disseminated with the drinking water and probably infected 100% of the human population before sanitary conditions became widespread in the 19th and 20th century. As we saw, the ulcer formation is really incidental, collateral damage, to the ingenious secretion of urease and neutralization of stomach acid. Even more alarming, it is now generally accepted that H. pylori is responsible for most cases of stomach cancer. So obviously, if we just treated this pesky bacterium to a dose of antibiotics, we’d solve the problem once and for all. Indeed, while the incidence of H. pylori infection in humans is decreasing in developing countries, presumably because of improving sanitation and increasing use of antibiotics, in the United States, the incidence of gastric cancer has decreased by 80% from 1900 to 2000.

However, there are always consequences; some of them unintended. Parallel to the decrease in H. pylori infection, there is an increase in the incidence of acid reflux from the stomach into the esophagus. And even more alarming, esophageal cancer is now the most rapidly rising cancer in the U.S. and Europe.

Fortunately, in most cases, we can deal with this problem quite easily. We have now powerful drugs that are called proton-pump inhibitors, such as Prilosec, that inhibit acid formation in the stomach and its reflux to the esophagus.

So here is another example of the delicate balance between us and our environment, in this case, our internal environment. Recent studies showed that gut bacteria may contribute to obesity or even to our mood. So before we indiscriminately eradicate the flora that inhabited us for millions of years and upset the delicate biological balance we live in, we should carefully consider the consequences.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.