Helicobacter pylori: the bacterium you should know more about October 20, 2006Posted by Hegemony in Health, Science.
Helicobacter pylori has been living with humans for a long time. But it was first characterized in 1875 as strange spiral bacteria in the stomach. However, it could not be grown in culture so it was disregarded. In 1982 two Australian doctors Barry J. Marshall and J. Robin Warren isolated the bacteria. It was eventually discovered that H. pylori plays a major role in the development of peptic ulcers and stomach cancer. Not long after research began to work out the role of H. pylori in humans, evidence indicated that the bacterium was disappearing. It seems that in developed nations antibiotics and better sanitation have decreased the incidence of H. pylori colonization. As it turns out, that’s not as good a development as one might think.
H. pylori is made up of 1.7 million base pairs comprising about 1550 genes. Remarkably, 6% of this bacteria’s genome is not shared by other strains of H. pylori. Humans share over 99% of our genome with chimpanzees, which are a completely different species. This tells us that H. pylori has many distinct yet functional forms that have developed over a very long time in humans.
One notable variant of this organism is the presence or lack of a protein called CagA. CagA is protein whose genes reside near those for a type IV secretion system. This seems to indicate that CagA utilizes this system to enter host cells. Once in the cell it causes the cell to signal to the immune system resulting in an inflammatory response. Those carrying strains of H. pylori expressing the CagA are more likely to develop gastric cancer.
Another variant of interest is the production of VacA. This is a toxin secreted by H. pylori that caused the formation of vacuoles in endothelial cells and (more importantly) turns off leukocytes in the area. Several different versions of this gene have been noted. The first were S1, S2 and M1, M2. The S1 variant had been divided into 3 distinct sub classes: s1a, s1b and s1c. It seems that the S1 and M1 forms produce the most potent version of the VacA toxin. Thus organisms with both CagA and VacA are the most likely to cause disease. The subtypes of the S1 gene have been used to track human movement in the past.
Different populations have different proportions of these genes. For example, s1b is prevalent in Spain and Portugal as it is in areas of Latin America settled by Spain and Portugal. The s1c variant was found in high numbers in some Amazonian areas as it is in the far east. This seems to show that H. pylori was with humans when they crossed the Bering Straight over 11,000 years ago. Genetic evidence from H. pylori can place it in the human population as far back as 60,000 years.
In developed nations only about 10% of people are colonized with H. pylori; whereas 70-100% of people are in developing nations. Humans have been carrying this organism for thousands of years and now the microenvironment is changing. The drop in H. pylori has corresponded with a drop in the incidences of certain types of stomach cancer as one would expect. However, we are seeing a massive jump in esophageal adenocarcinoma, rising 7-9% each year. This is a cancer of the esophagus just above the stomach with a 5 year survival rate of 10%. The primary risk factor gastroesophageal reflux disease (GERD) has gone up; it was completely unknown before the 1930’s. The correlation is hard to miss, When H. pylori colonization decreased these diseases increased.
The key is a negative feedback loop with the host. Humans and H. pylori have been coexisting for so long that there are certain adaptations involved on both sides. The bacteria use various signals to protect themselves as well as the host. An example is pH; if the stomach is too acidic the bacteria die, if it’s not acidic enough opportunistic pathogens can invade. When the acidity is high H. pylori will secrete large amounts of CagA. The resulting inflammatory response will lower acidity. The opposite is also true, low acidity slows production of CagA allowing the acidity to rise. Carrying H. pylori without the CagA gene results in weaker pH control and in people without H. pylori this regulation does not happen at all. If there is no control it is more likely that the esophagus will be exposed to highly acidic stomach contents as in GERD.
In the not too distant future could H. pylori be used as a probiotic? It is certainly not outside the realm of possibility. It is certainly more likely than using species of lactobacillus that are not so intertwined with humans. As we learn more about H. pylori it may become possible to give an individual the right bacterial load of Helicobacter to result in the lowest likelihood of stomach and esophageal cancers.