The Frenemy Inside You: tales of bacterial cooperation and collusion

You are roughly half bacteria. In terms of cell number, that is. It’s a disorienting reality to swallow, but the body that allows you to dance and digest is utterly dependent on the work of millions of bacterial collaborators. They colonize your gut, pulling off complicated chemical reactions to produce nutrients necessary for your survival (biotin and vitamin K, to name a few). They patrol your skin, forming complex communities that ward off dangerous disease-causing interlopers. And, research published last week shows that they may also affect brain development and the efficacy of cancer drugs.

The bacterial panoply that cooperates so closely with your human cells is as unique to you as a fingerprint – no two people share exactly the same set of bacterial species. Recently, the impact that your “microbiome” has on your health has begun to get the attention it deserves. Study after study has found that sick people tend to have unusual bacterial fingerprints.  

To evolutionary biologists, the interdependence of bacterial and animal cells is not surprising – we’ve been working together for eons. In fact, you carry a historical remnant of bacterial cooperation within every single cell in your body. The mitochondria (powerhouse of the cell!), small membrane-bound compartments inside each of your cells, are responsible for producing all of the energy your body uses to power its functions. Mitochondria are so ubiquitous inside our bodies that you might be surprised to learn that they were once bacteria. Roughly 1.2 billion years ago, a small bacterium — the first mitochondrion — was swallowed up by a much bigger cell. It continued to produce energy within the larger host, and over time the two began a fast friendship that allowed the pair to increase in size and complexity, eventually becoming the animal cells we recognize today. That tiny bacterium was the ancestor of all your mitochondria! Talk about teamwork.

A microscope image of a mitochondrion.

However, like any relationship, our friendship with microbes has its ups and downs. We are undeniably reliant on bacteria, but they occasionally misbehave. We’ve just begun to scratch the surface of understanding how bacterial communities interact within our bodies, and the influence they wield over us. Two studies published last week highlight this complexity by demonstrating what can go awry when the peaceful collaborations are disrupted.  

Scientists at Harvard Medical School (with help from collaborators at MIT and UMass, Worcester) describe a link between a particular type of bacteria (segmented filamentous bacteria, to be precise) in the guts of pregnant mother mice, and developmental defects in their babies. The bacteria are long and snake-like and undeniably scary looking. When researchers fed these snake-like bacteria to pregnant mice, the mothers-to-be produced fewer of a specific type of immune cell, and pumped out more inflammatory chemicals into their bloodstream. But the bacteria didn’t only impact the mothers: it impacted their babies. Their offspring failed to engage with their fellow mouse cagemates, and buried toys over and over again.

How could a mother’s microbiome have a direct effect on the development of her baby’s brain and behavior? It’s long been known that when a pregnant mother’s immune system is stressed by the presence of bad bacteria, it broadcasts chemical signals to the embryo through the blood. With a connection this deep between the immune systems of mother and child, some kind of link between the well-being of the mother’s microbiome and that of her offspring is actually not far-fetched. But before you rush out to buy kimchi in bulk, it’s worth noting that this study is describing the particular behaviors of mice in response to a single type of bacteria. It’s adding to a larger conversation about the microbiome and its relationship to human health, and we still need more information before assuming bacteria are to blame for human developmental disorders.

A mom mouse and her mouse babies.

A second paper implicates another set of bacteria in a nefarious role: contributing to drug resistance in colon cancer. How some tumor cells evade chemotherapy has been a longstanding and frustrating problem in cancer treatment. Biologists at the Weizmann Institute of Science in Rehovot, Israel, have recently discovered that these villainous drug-resistant tumor cells have secret bacterial accomplices. Specific species of bacteria are able to break down a common colon cancer drug into a harmless form, allowing the tumor to continue its growth as if no drug was ever administered!

One of the experiments the researchers did to prove this point is pretty wild. They altered the genes of the “accomplice” bacteria to make them glow green, then injected these “labeled” accomplices into mice with colon cancer — the microbial equivalent of putting a wire on a confidential informant. The bacteria glow so brightly that scientists are able to detect their green light from outside of the mouse! They gave half of the mice an antibiotic that kills the accomplice bacteria, and then treated them with the anti-cancer drug. Mice without bacteria responded to the drug (their tumors shrunk), and mice who had the bacteria did not.

The group then scoured human colon cancer samples for these “accomplice” bacteria. They found the bacteria in three quarters of colon cancers that are often treated with the degradable drug. When they looked at the samples under a microscope, they found the bacteria snuggled up within the tumors – pretty damning evidence that they’re in the right spot to break down the drug and give the tumor an edge.

If odious alliances like this are widespread, we might be able to dramatically improve treatment paying attention not only to the human cancer cells, but to their bacterial companions. That being said, cancer biologists are well-aware that a single “miracle cure” is unlikely: cancer is a multi-faceted disease, with many interlocking molecular parts. Still, any addition to the arsenal of treatments available to oncologists is a valuable contribution to medicine and to science.

It’s becoming clearer and clearer that your body is chock full of alliances, both healthy and harmful, between your human cells and their bacterial counterparts. There’s still a lot to be done to illuminate the seedy underbelly of the microbiome, and investigators are hard at work. Whether friend or foe, it’s time to appreciate the role of our tiny bacterial hitchhikers!

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