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

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

April 12, 2018 0 By Santiago
Reading Time: 5 minutes

Yet another Q&A, because it’s fun. In our last post you saw that microorganisms in your digestive tracts 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 can have a look at it here. This time, we want to know, what controls the microbiome?

Seems like the gut bacteria are responsible for everything nowadays. Your exercise results, mental health, illnesses and hunger, all can apparently 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 realise 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 a correlational effect. To make it even more confusing, it sometimes is hard to pinpoint whether the gut bacteria alters your physiology and overall health or whether it’s the other way around.

This is not me trying to bash on 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 realise that everything has limitations. Just like CRISPR-Cas9 biotechnology appeared as a Messiah to finally exposed 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 emphasised 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 from, we also want to know what regulates our microbiome compositions. We want to know if it is due to our genetic background or our 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 contribution by the environment.

So then, if your microbiome is mostly dependent on environmental factors rather than genetics, then it should also be in your control. There must be things you can do about it. How about transferring stool (you know: poop) from healthy to sick or fit to unfit? A so-called stool or faecal 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 one 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 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 had a reduced response to inflammation-inducing agents, such as viruses and mutagens, compared to 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 condition of the latter 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 against different types of diseases. Notice how I said “mice”. It’s a mouse study, and as we know, 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 can 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 actually misrepresented due to an atypical lab-mouse microbiome?

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

Obviously, 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 actually 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 performed, especially in immunotherapeutic research. Transferring patient poop to a mouse ‘avatar’ could better reflect therapeutic responses in real life. Not bad at all.

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

To be honest, the question is a teaser. A cliff-hanger if you prefer. As you’re slowly starting to understand by now, this is something that will be covered on our next post (Part 3). This way, I can make a trilogy out of this theme. Like the Matrix, you know.

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 and 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 the 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 the new knowledge, while feeding your bacterial friend with the good foods.

Did you miss a part of the microbiome series?

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

Share the love!