A new study in mice uses cutting-edge imaging techniques to investigate how H. pylori, which are present in around half of the humans on earth, survive and thrive in the stomach.
Gut bacteria are one of the hottest topics in medical science today.
As scientists add to the surprisingly long list of conditions that may involve bacteria, understanding more about how they outwit both medications and our immune systems has become increasingly important.
One bacterium that has an incredible ability to colonize humans is Helicobacter pylori. In fact, it is estimated to live in the stomachs of around half of all humans.
It tends to first enter humans when we are young and then remains in situ throughout much of an individual's life.
In most people, the bacterium appears to do no harm; however, in some, H. pylori can lead to gastric cancer and peptic ulcers. One author writes:
"Approximately 75% of the global gastric cancer burden and 5.5% of malignancies worldwide are attributable to H. pylori-induced inflammation and injury."
The secrets of H. pylori
Despite the prevalence and ramifications of H. pylori infection, understanding how the bacterium behaves in our stomachs has proved challenging.
Researchers, many from Stanford University School of Medicine, in California, recently carried out a set of studies to understand how H. pylori remain in the stomach so successfully. The scientists also hope to provide clues as to how these bacteria might be displaced.
Using cutting-edge visualization tools, the scientists identified H. pylori's hiding place. They published their findings recently in the journal PLOS Biology.
H. pylori are highly specialized to colonize the stomach, which is a particularly inhospitable place to live — it is essentially a vat of hydrochloric acid. Despite this, the bacteria thrive and can maintain their position for decades.
Aside from the intense chemistry of the stomach, its cells are replaced rapidly, making it even more difficult to keep a foothold in the stomach.
Antibiotics can kill H.pylori but, commonly, they do not eradicate the bacteria entirely, and the population soon regrows. Senior author Dr. Manuel Amieva explains that "The reemerging strain is invariably just the same as the one thought to have been eradicated."
This infers that H. pylori have a hiding place, somewhere, out of harm's way, that the bacteria can regenerate in safety. The authors of the recent paper wanted to uncover this hiding place.
How H. pylori hide
H. pylori have spinning flagella, which are long, whip-like structures that enable the bacteria to move through their environments. Scientists believe that the bacterium uses this miniature onboard motor to tunnel into the stomach's mucus layer.
The mucus layer protects the stomach's lining and, therefore, might offer the bacterium some protection, too.
The scientists found that this tactic certainly plays a part, but they also discovered another way that the bacteria protect themselves.
To investigate, the researchers infected mice with two strains of H. pylori; one was genetically modified to emit fluorescent green light, the other produced fluorescent red light. They also used a technique called CLARITY, which allowed the scientists to "move through" intact tissue and develop a 3D image of where the bacteria had settled in the mice's stomachs.
Earlier research by the same group showed that H. pylori hide in gastric glands, which are tiny pits in the wall of the stomach.
If a particularly hardy bacterium makes it into one of these pits and multiplies, they become incredibly difficult to dislodge. The scientists could not identify exactly why they should become so entrenched, but they believe that it might be because each gland has just one entrance, the diameter of which is only around four times wider than H. pylori.
Mapping the spread
The new research investigated the way that H. pylori spreads out once it has arrived in an animal. The scientists expected the two strains of bacteria (which were identical aside from their coloration) to mix and become a blended population of both colors.
However, they found that once a bacterium — either red or green — had set up shop in a gastric gland, it reduced the ability of other bacteria to enter. So, even though these bacteria were all the same strain of the same species, the researchers determined that they would outcompete their own kind.
Once a red or green bacterium had colonized one gland and replicated, they would take over positions in neighboring glands; this created a patchwork pattern of red and green across the lining of the mouse's stomach.
It is still not clear exactly how each bacterium takes over a pit and claims it as its own. However, in one of their experiments, the scientists used bacteria that had been engineered to lack the chemical sensory machinery that they use to navigate; these bacteria could not set up exclusive red- or green-only colonies.
In the recent past, probiotics have been used to get rid of so-called bad bacteria; but, as Dr. Amieva explains: "It's not enough to find a good probiotic strain that can survive in the organ you want it to live in. You need to create space for it."
For instance, Dr. Amieva suggests one approach: Tempt the bacteria from their hiding places, then replace them with a less virulent bacterium.
This study provides a clearer picture of how H. pylori settle in our stomachs. Hopefully, in the future, this information might help us find a way to remove it.