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The Microbiome and Its Myth-Making Machine

If you have heard something very specific about the microbiome, odds are it’s wrong

As promising new discoveries are made in the health sciences, the telephone game begins. Scientists put their best foot forward when presenting their results. The public relations department at their institute further digests their findings and adds a dash of hype. Journalists amplify and simplify, social media influencers garble the message, and start-ups capitalize on the hype to sell unproven health solutions. Before you know it, you’re grabbing a cup of coffee while your colleague tells you that they heard cancer was caused by bad bacteria in your gut. Better buy more yogurt, you think to yourself.

We have become obsessed with the microbiome and for good reasons. Its research field, which is dedicated to studying the vast community of microorganisms (including bacteria) that grow on and inside our body, is expanding rapidly as new tools allow researchers to identify these little bugs so much faster than before. There was a time, though, when we did not know that the human body was colonized by these microorganisms. That started to change when Dr. Theodor Escherich observed a particular bacterium in the intestine of children in the 1880s. That bacterium would much later be named Escherichia coli or E. coli in his honour.

Scientists have come a long way since then, especially in the last couple of decades, which means the telephone game has been busy spreading myths and distortions about the microbiome. Antiquated figures still make the round, while fuzzy knowledge is sharpened into an unearned certainty in order to sell an intervention that may or may not work.

It's time to correct the bacterial record.

Wrong number

Perhaps the most common myth about the microbiome is that all of these bacteria actually outnumber our own cells ten to one. We would thus be more bacteria than human.

That figure—ten to one—has been tracked down to a 1972 paper, in which the author did a simplistic, back-of-the-envelope calculation. A much more thorough and recent estimate, published in 2016, puts the ratio at approximately one to one, meaning roughly as many bacteria living in and on our body as the number of human cells we are made of.

The weight of all these microorganisms has also, somehow, ballooned up and become a popular factoid. It is said to be one to two kilograms! The authors of a paper published last July addressing myths and misconceptions surrounding the human microbiome were unable to trace the origin of this impressive figure. Corralling all of our bacteria and putting them on a scale is much more likely to yield a mass of 200 to 500 grams. That’s equivalent two to four peeled bananas, for comparison.

While our best estimates fall short of the legendary numbers you may find in a magazine, the size and diversity of our microbiome are still spectacular. Scientists believe that somewhere between 500 and 1,000 different species of bacteria exist in and on our body at any one time. Each species has its own set of genes, which differs from that of another species. This means there is much more genetic diversity in our microbiome than in our own cells. And the microbiome does not stop at bacteria. It also includes yeast, fungi, archaea and, depending on whether you think of them as being alive or not, viruses.

Millions of these tiny beings live on our skin alone. Bacteria form distinct ecosystems on different parts of our skin depending on whether it is dry, moist, or oily. Microorganisms as a whole have taken up residence on our skin, in our gut, and inside the vagina. What their role is, however, is only beginning to be understood, but that has not stopped many people from taking unjustified leaps.

The one true cause of all diseases

Facts about our microbiome are not just for sharing at dinner parties. They can also make us wonder how actionable they are. If you have to take a course of antibiotics, should you also take probiotics to avoid getting diarrhea? After all, we know that antibiotics can upset the bacterial equilibrium in the gut. Thus, probiotics, which are made up of “good” bacteria, are often sold as a safeguard against this.

The truth is that, while many of us want to turn to microbiome experts for a prescription, all we can get right now is a vague answer. There is strong evidence that taking probiotics will prevent antibiotic-associated diarrhea. The problem is that we do not know much beyond that. Which bacterial strains, which dose and for how long: these are all questions that have yet to be answered, as the clinical trials probing this area of inquiry have used all sorts of probiotic preparations, with many not adequately documented.

These same probiotics are often sold with the suggestion that they can prevent or treat various illnesses, supposedly by boosting the power of your microbiome or bringing it back into equilibrium. But as a medical summary points out, “enthusiasm for [the] use of probiotics has outpaced the scientific evidence.” And since probiotics are not pharmaceuticals but dietary supplements, their regulation is more easygoing. Companies simply do not have to prove that their labels are accurate.

But putting aside the microorganisms we can add to our body, the ones already there are even now being fingered as dastardly culprits. You may have heard that many diseases are caused by disturbances in our microbiome. Break the fragile stability of our microscopic ecosystems and cancer waltzes right in, or so the thinking goes. This is, however, a gross simplification of the state of our research.

Studies have shown that, compared to healthy individuals, people with certain medical conditions, like inflammatory bowel disease, have changes in their microbiome. More than that, experiments have been done where healthy, germ-free animals receive a transplant of bacteria from a diseased donor, and the disease appears in these healthy recipients. We also know that the presence of the bacterium H. pylori (which causes stomach ulcers) is associated with a higher risk of developing stomach cancer in humans. Adding up all of this data, the presence or absence of certain bacteria clearly has an impact on disease risk. It is thought that factors in our environment combine with genetic predispositions to influence, positively or negatively, our microbiome. This microbiome then interacts with our immune system, and this can pave the way for disease.

That being said, precision still eludes us. For instance, the bacterium P. acnes has been tied to acne, yes, but almost all adults have been colonized by it, yet only a minority have acne. Another bug, P. copri, was found in one study to improve glucose metabolism, but in another study, it made glucose intolerance worse. Rarely is a single bacterial species solely good or bad. It depends on where it finds itself and which other bacteria surround it. Much like how we used to think that all diseases were caused by mutations in a single gene before realizing that common diseases are actually caused by mutations in many genes interacting with the environment, the complexities of the microbiome are slowly being unfurled by scientists.

Because studying the microbiome is a lot more complicated than it looks. Yes, researchers are no longer limited to seeing which species can grow in culture in the laboratory; they can directly sequence the DNA of certain genes in a sample to figure out which species are in there. But figuring out what is really going on is far from simple.

The microbiome of laboratory animals is influenced by how they are bred, as well as the food they are fed, the acidity of the water they drink, and the bedding they use. Animals sharing a cage may begin with different gut microbiomes, but if they start eating each other’s poop (and it happens!), that can change.

In humans, the microbiome can be influenced by more than just the presence or absence of a particular disease, but by a veritable laundry list of factors: diet, age, pregnancy, the use of antibiotics and other drugs, intestinal motility, stool frequency and consistency, genetic make-up, exercise regimen, sleep deprivation, stress, occupation, and cohabitation with pets. Even the site on the body from which the microbiome is sampled for the purpose of research will be important, as the bacteria that grow on the armpit will be different from the ones found in the gut. And the microbiome changes over time, too. Its diversity increases until adulthood, before remaining stable for a while and slowly declining with age, and while it is somewhat resilient to changes, it can vary over time as our diet and other lifestyle factors change.

It is thus much too soon to say that obesity or cancer or ulcerative colitis is caused by a dysfunction of the microbiome and that we know exactly what those changes are and how to fix them. Research into the microbiome is finally moving away from simply describing what is there and into understanding the mechanism of how it all works together, after which clinical interventions will finally be on the horizon. But apart from the use of fecal transplants to treat a bad C. difficile infection, we are not there yet.

The love bug

Factoids about the microbiome can be interesting to share, but accuracy should be top of mind. Repeating that we have ten times as many bacteria as human cells may sound impressive, but it’s simply wrong. If you are looking for better factoids to share around, here is one I stumbled upon in my readings.

So-called identical twins (who are not genetically identical, but highly, highly similar with tiny variations) have fairly distinct microbiomes, barely more similar to one another than the ones found in fraternal twins. This means that our microbiome is heavily influenced by our individual environment.

I was going to end with a saucier factoid, but the microbiome myth-making machine struck again. I wanted to share that, as reported in a review article published in the prestigious Nature Medicine journal, opposite-sex couples engaging in intercourse share bacteria to the point where, over time, the species of bacteria found in the vagina and on the penis of sex partners become more and more similar. It would give “catching the love bug” a whole new meaning.

However, it turns out that the authors of this review article got it wrong. The study they link to only demonstrated this similarity when the woman had bacterial vaginosis, a condition which is thought to be sexually transmissible, although the specific bug that transmits it has not been identified. Without bacterial vaginosis, the penile and vaginal microbiomes were not matched.

Distortions, legends, and falsehoods. The microbiome, as it turns out, is full of them. We should tread carefully.

Take-home message:
- The number of microorganisms making up the human microbiome is not ten times larger than the number of human cells; rather, the best estimate we have is that they are roughly equivalent in numbers
- There is strong evidence that taking probiotics can prevent the diarrhea that is associated with a course of antibiotics, but we do not yet know enough to recommend specific strains, dosages, or duration for these probiotics
- Many diseases have been associated with changes in the microbiome, but at this point, we cannot say that these changes cause the diseases, as there are too many variables at play


@CrackedScience

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