Can the human microbiota cause cancer? Part 2: Inflammation

As I intimated in last week’s post, bacteria can cause cancer! But how? How does cancer develop in the first place? If you want a seriously in-depth answer to this question, I highly recommend Siddartha Muhkerjee’s “Emperor of All Maladies.” Holy crap, that book was good.

More simply, cancer arises from changes in the normal genetic code that cause cells to maniacally replicate and form tumors. These changes can be inherited (like that devilishly handsome chin dimple), induced from exposure to things in the environment, or you draw the world’s unluckiest lottery ticket when the normal, rare mistakes of the cellular replication machinery occurs in a critical gene.

Bacteria cause cancer through the middle avenue: environmentally-induced changes. Typically environmental mutagens physically interact with the DNA to cause mistakes in its replication. Since bacteria do not crawl inside the cell’s nucleus and sucker-punch your DNA, it suggests the changes occur indirectly. As mentioned in Part 1, Helicobacter pylori is the classic example of a bacterial carcinogen. H. pylori is an opportunistic pathogen, meaning it can live happily inside your body without causing disease, until the conditions are right. The main etiology of H. pylori is not cancer, but gastritis and ulcers. A bold experiment by an Australian doctor in true, Outback Steakhouse-style proved H. pylori causes ulcers by growing up a flask of the bacteria in the lab….and chugging it.

http://www.geekdecor.net/erlenmeyer-flask-spirit-decanter/

He immediately felt terrible, vomited, and developed ulcers. Ta-da! SCIENCE.

So we’re in the 1980s, and we know H. pylori can cause gastritis and ulcers, thanks to Dr. Chugs (I mean…prestigious, Nobel-Prize winning scientist Dr. Barry Marshall). The scientific community has already been postulating that gastritis and ulcers are a risk factor for stomach cancer. It’s white-haired scientist two-piece puzzle time! H. pylori infection could lead to stomach cancer.

To actually get some pesky DATA to back up this hypothesis, an unlikely country steps up to the plate: Japan. In my small, uncultured mind, I would guess the Japanese diet and lifestyle should decrease gastrointestinal issues. However, what I don’t have a stereotype about, is the infection rate and virulence of endogenous Helicobacter strains. The H. pylori strains originating in East Asia are much more virulent than Western strains and infect more than 70% of the population, a rate 20% higher than the rest of the world. A particular study on a cohort of Japanese patients revealed that 3% of those infected with H. pylori developed stomach cancer while a whopping ZERO percent developed cancer in the absence of the bacteria.

Gary Larson’s “Early Microscope”

Alright Amanda JEEZ you still haven’t answered the question you posed two weeks ago. How do bacteria cause cancer? The answer is pathogenesis plus chronic inflammation. The Helicobacter strains from East Asia are more likely to contain virulence factors. These virulence factors are injected directly into the stomach epithelia and wreak havoc on intracellular signaling. Now, inflammation occurs because your body can detect those virulence factors and says, “YIKES, let’s muster some immune cells to this location and get rid whatever’s causing this!” But, the thing about Helicobacter…it has been living in humans for about 50,000 YEARS. We’re talking about a time when the sewing needle was the hot new technological advance and a straight up Neanderthal could be your neighbor. We’re talking too primitive for CAVE PAINTINGS.

Anyway, I digress. The point is Helicobacter, a bacterium with its own incredible ability to mutate and adapt to new environments, has had the chance to adapt to the human body for 50,000 years. So when the body unleashes the immune system on H. pylori, it’s like “oh, this old trick,” and persists. Unable to dislodge H. pylori, the inflammation becomes chronic. Scientists have shown that Helicobacter colonization of mice can lead to progressive inflammation and tumor formation [1].*

And finally, HOW specifically does inflammation lead to cancer?

  1. Collateral tissue damage from deadly molecules usually reserved for the killing of pathogens (see above: H. pylori evades the immune system but never stops activating it…).
  2. When something is inflamed, blood vessels dilate and can even be built from scratch to facilitate the movement of immune cells (which is why inflamed things are red and hot from your red, hot blood). Young cancer cells take advantage of this by gobbling up all the nutrients to sustain their insane replication rate leading to full blown tumors.

There you have it. Chronic inflammation from an evasive, opportunistic pathogen can lead to cancer. But what about the gut microbiota? Scientists have been unable to isolate a single bacterium that leads to colon cancer…what’s going on in there?? Stay tuned.

Happy Thanksgiving!!! A toast to you and yours. -Amanda

1. Fox JG, Li X, Yan L, Cahill RJ, Hurley R, Lewis R, Murphy JC. Chronic proliferative hepatitis in A/ JCr mice associated with persistent Helicobacter hepaticus infection: a model of Helicobacter-induced carcinogenesis. Infect Immun. 1996;64:1548–1558.

*Do you RECOGNIZE a NAME perhaps on this PUBLICATION?! That’s right! I have my very own white-haired scientist! HURLEY R is MY DAD.

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