H. pylori: old friend, new enemy?


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Up until the 1980s, doctors and scientists believed that gastritis and stomach ulcers were caused by peptic acid eroding the lining of the stomach. Then, two scientists from Australia, Dr. Barry J. Marshall and Dr. J. Robin Warren, made a discovery that changed everything: most people who suffered from ulcers also had a bacterial infection that was causing inflammation of the stomach lining. The newly discovered bacterium was named Helicobacter pylori, and doctors soon found that treatment with antibiotics could effectively cure most ulcers.  Good news for ulcer patients.

In 2005, Marshall and Warren were awarded the Nobel Prize for Physiology or Medicine for discovering H. pylori and its role in gastric disease, which led to wide-spread news and media coverage. People everywhere were hearing about this ‘bad stomach bacteria that you didn’t want to have’, but a few years have passed, and we are beginning to understand that it’s just not that simple.  You might want to have it, or you might not… it depends…

We now know that humans (along with many species of animals and birds) have been colonized by H. pylori for at least 60,000 years, and probably longer. We know this because geneticists can calculate average mutation rates of the bacterium’s DNA as it travelled along in the first Homo sapien exodus from Africa.

We seem to have lived together quite peacefully with H. pylori until very recently in human history. Not long ago, just about every human on the planet was colonized with H. pylori. It was (and still is) part of our normal microbial flora, but today only about half of all people are still carrying it.

Ironically, infection with H. pylori has been linked to gastritis and peptic ulcers, both of which have been on the rise in the last hundred years or so, just when the incidence of H. pylori infection is rapidly declining.  And, peptic ulcers were very uncommon before the 20th century, when just about everyone was infected with H. pylori.

Also practically unheard of before modern times was gastroesophageal reflux disease (GERD), a disease that has been increasing steadily, and is most common in people who aren’t colonized by H. pylori at all. GERD is not common in people who have H. pylori. So, here we have a bacteria that we apparently lived peacefully with for much, if not all, of our time as Homo sapiens, not even knowing it was there, and now suddenly we can’t live with it, can’t live without it…

What went wrong?

As it turns out, being colonized with H. pylori causes your stomach to produce less acid, and since humans have been colonized with the bacterium for so long, the ‘less acid’ state has become normal for us. Now, remove the H. pylori from the equation, and what happens? That’s right, a lot more acid is produced, and the incidence of GERD goes up as well.

But then why the ulcers?

Most people who are colonized with H. Pylori never get ulcers, but those that do have an abnormally low Treg response in their gastric system. ‘Treg’ is short for ‘regulatory T cells’, and their job is to keep the immune system in check, for example turning off the inflammatory response after fighting off a disease, or preventing the immune system from attacking things that aren’t really dangerous to us (and causing allergic reactions).

We have learned that much of our Treg response depends on our immune system learning early on in childhood what is friend and what is foe, and exposure to a large variety of bacteria early in life is important for all that to be sorted out. Yet with the advent of antibiotics, disinfectants, and improved sanitation, we are exposed to far less bacteria, both ‘good’ and ‘bad’, now than ever before in our history. Studies have already shown that children raised on farms where they are exposed to a wide variety of bacteria have far less incidence of asthma and other autoimmune diseases.

When we are not exposed to H. pylori as a child, our immune system does not recognize it as part of our normal gut flora when we acquire the bacteria as an adult. This means the Treg response doesn’t effectively control inflammation in the lining of the stomach, and ulcers can result. The excessive use of antibiotics may also have selected more virulent strains, which outcompete the more harmless ones..

And cancer?

Yes, prolonged infection with H. pylori is linked to stomach cancer, or at least it has been in the recent past, and here’s where things get even more complex. It seems that you need pretty close contact in order to pass H. pylori from person to person, and therefore in the history of our co-evolution, families, tribes, and other close-knit groups tend to share the same strain of the bacteria. Over time, people and their local strain of H. pylori adapt to one another’s small differences.

But now people have started moving around faster and farther than ever before, and are constantly encountering new strains of H. pylori. If you’re already colonized by your own familiar strain, that’s not really a problem. But if you acquire H. pylori for the first time from a ‘stranger’, it’s more likely not to agree with you and cause inflammation and other changes that might eventually lead to cancer.

A fascinating study of two populations in Colombia illustrates how closely H. pylori has evolved with its human hosts. One of these populations lives in the mountains, and is of Amerindian descent. The other population, living near the coast, is of largely African descent. Both populations have the same rate of colonization with H. pylori, yet gastric cancer rates are much higher among the Amerindian population.

Why?

When scientists sequenced the genomes of the H. pylori, they found that the bacterial strains colonizing the coastal population were largely of African descent, as were the people. But the bacteria colonizing the Amerindian population were largely Southern European. This mismatch seems to have led to a greater incidence of cancer.

Unfortunately, the absence of H. pylori also leads to an increase in cancer, because of the association of GERD with esophageal changes that can eventually become malignant.

We still have lots to learn about our physiological relationship with microbes, but now that the microbiome has moved into the spotlight, we are on the verge of a new age of understanding, and perhaps a more targeted and refined approach to medical care.

 

References

Atherton, J.C. and Blaser, M.J. 2009. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest. 119(9): 2475-2487

De Sablet, T. et.al. 2011. Phylogenetic origin of Helicobacter pylori is a determinant of gastric cancer risk. Gut 60(9): 1189-1195

7 thoughts on “H. pylori: old friend, new enemy?

  1. I’m currently waiting for the results of the biopsy taken during an EGD to dilate my esophagus. My doctor said I have gastritis and with my symptoms it could be H Pylori. I’m very worried about this because I don’t know much about it and I already have enough other medical problems to worry about. Thanks for sharing this information.

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