DNA person surrounded by immune cells and food.

The gut microbiome (Part 2) – what controls the microbiome?

Yet another Q&A because it’s fun. In our last post, you saw that microorganisms in your digestive tract are a big part of your life. Much of the bacteria in your intestines, for example, live in symbiosis with you, which can affect many aspects of your life. If you missed it, you could have a look at it here. This time, we want to know what controls the microbiome

Seems like gut bacteria are responsible for everything nowadays. Your exercise results, mental health, illnesses, and hunger can be traced back to your microbiome. Don’t be surprised if it in the future will serve to explain the financial situation in Greece.

Also, prepare for the sales pitch because apart from stimulating the development of research-based therapies, the microbiome’s sudden fame attracted business-minded people to the table. Because there are a lot of physical and mental conditions related to the microbiome, and they could potentially be treated or prevented. The field is a gold mine.

How important is it to understand the microbiome?

With that in mind, it’s important to realize that the microbiome research field is relatively young. Much of our knowledge is still at a premature stage. For example, although we can associate bacterial composition with health conditions, diseases, or fitness levels, it’s not always clear if it’s a direct or correlational effect. To make it even more confusing, it is sometimes hard to pinpoint whether the gut bacteria alters your physiology and overall health or the other way around.

This is not me trying to bash the microbiome field. I would never do that. I love it, and I love where it’s going! Still, they are important complications to mention, and we also need to realize that everything has limitations. Just like CRISPR-Cas9 biotechnology appeared as a Messiah to finally expose possible weaknesses, the microbiome seems to be wearing a similar piece of cloth. The problem is that it can be tempting to explain everything by saying, “it’s the microbiome, bro”. Other physiological factors didn’t just cease to exist just because we happened to discover and emphasize the importance of the gut microbiome.

Nevertheless, it has a fundamental effect on your body and health. So, it’s important to ultimately understand the true roles of the gut microbiome, how they come to be and how we can use it to our advantage.

Is your microbiome composition dictated by genes or environment?

Aaah… the good ol’ nature vs. nurture conundrum. Just as we want to understand where stupidity originates, we also want to know what regulates our microbiome compositions. We want to know if it is due to our genetic background or environment. Why? Because it either makes us predetermined victims (genes dictate) or masters of our destiny (environment dictates). What’s it gonna be?

While there are conflicting publications about this, an interesting article in the journal Nature aimed to tackle this question. They used large samples of healthy individuals with different ancestral origins. The conclusion was that “the microbiome is not significantly associated with genetic ancestry” or genetic variations between individuals. They did, however, demonstrate a significant environmental contribution.

So then, if your microbiome is mostly dependent on environmental factors rather than genetics, it should also be in your control. There must be things you can do about it. How about transferring stool (poop) from healthy to sick or fit to unfit? A so-called stool or fecal transplant.

Can we transfer poop from healthy to sick?

A publication in Cell last year showed it in mice. The researchers caught wild mice and compared their microbiota to the microbiota of laboratory (lab) mice. They used traps to catch them. But go ahead and imagine lab-coat-wearing researchers in the wild, hunting mice with a lasso, if that’s your thing.

Lab mice live in sterile environments. This is convenient in research because it allows researchers to reproduce and control experiments. But do these conditions represent the ones of patients? Not much, unless you’re a bubble boy. The unnatural environment of lab mice leads to unnatural microbiomes.

As you might have expected, the researchers found that the wild mice had a health advantage over lab mice. Wild mice responded less to inflammation-inducing agents, such as viruses and mutagens than lab mice. Importantly, they found that the disadvantages of the lab mice could be reversed by transplanting stool from wild mice into their systems. In other words, a simple poop upload from a fitter to a weaker mouse could improve the latter’s condition and make it fitter.

If you ask me, this study contains at least two important take-home messages:

  1. The obvious one is that a well-developed microbiome can keep mice healthy and resistant to different types of diseases. Notice how I said “mice”. It’s a mouse study, and we know that conclusions from mouse studies are not necessarily translatable to human conditions. However, it could be time to fix that gut environment of yours still.
  2. Unfortunately, we also learned that the abnormal microbiome developed in lab mice could affect the outcomes from animal experiments, for example, when we study treatment responses. The question is, how much of our knowledge based on mouse studies is misrepresented due to an atypical lab-mouse microbiome?

Although the latter point doesn’t directly translate to your well-being, it can have massive implications for the discovery and development of future therapies.

Of course, we cannot keep laboratory mice in the wild, hoping that they’ll represent our patients better. Yet! However, an approach to overcome this problem is to transfer the intestinal microbiome from patients to laboratory mice. To create an “avatar mouse” and study treatment responses. It may sound like science fiction (maybe not, but for the sake of flow, let’s say it does), but it’s something that’s already been performed, especially in immunotherapeutic research. Transferring patient poop to a mouse ‘avatar’ could better reflect real-life therapeutic responses. Not bad at all.

Can I apply this knowledge now (as a human being)? And if so, how?

To be honest, the question is a teaser. A cliffhanger if you prefer. As you’re slowly starting to understand by now, this will be covered in a future post.

For now, you know that the microbiome plays an important role in your body. It alters your physiology, health, and, to some extent, your habits (think food and eating). You also learned that the environment significantly shapes your microbiome composition, not your genes. Finally, you also learned that the microbiome composition of lab mice is very distinct from their wild relatives, making the lab mice more susceptible to inflammatory agents. Possibly messing up mouse experiments. As an insider, I can tell you: it happens. Although, on a positive note, this seems to be a reversible thing.

I think that’s quite some information already. Use it wisely. There’s a weekend coming up. Impress your human friends with new knowledge while feeding your bacterial friend with good foods.

Did you miss a part of the microbiome series?

The gut microbiome (Part1): The good, the bad and the slacker

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