Thanks to microbes

What is the microbiome, in simple terms? The set of microorganisms that live with us. Each person is an ecosystem in which, approximately, half of the cells are human and the other half are microbes. And we live with them in a situation of mutualism: we provide them with nutrients for their survival and they allow us to be healthier. It is a kind of pact that makes us who we are and live as we live.

Are we really a multitude rather than a single individual? Microbes are throughout our body; but more than 95% are found in the intestine. And, of that 95%, more than 90% are in the colon. The most recent calculations indicate that we have one microorganism for every human cell and that the global weight of the bacteria in our body would be about 800 g. We are truly surrounded by millions of them. There are more bacteria in our body than stars in the Milky Way! And most are beneficial for our body, what's more: they are usually essential for life.

So, do we have microbe genes in our DNA? Exactly. We have the human genome, which is inside eukaryotic cells. And then we have the microbiome. The so-called second genome. Although, in any case, it would be a metagenome: a sum of bacterial genomes that live in our body.

What are the consequences of this encounter between genes and microbes? A lot. One is that bacteria interact with our cells and make their functions sometimes different. The other is that modifying human genetic content is very complicated but, in principle, we can change this metagenome by eliminating, for example, a few bacteria so that, simplifying a lot, we can remove genes that do not interest us. The microbiome not only reveals to us that the nature of the human being is much more complex than we imagined, but also reveals that there is a very significant part of us that we can modify.

Does each person have a unique microbiome? We all have common patterns. The microbiome could be used to recapitulate the evolution of eukaryotic beings by making a phylogenetic tree of chimpanzees, gorillas, humans… You would get the same tree as using genes. But it is also true that in different parts of the world the relative abundance of some bacterial species varies greatly: in Africa and in diets richer in fiber there is a predominance of prevotella, while in areas where more meat or processed foods are eaten there are more bacteroides. And this can be taken down to the individual. There are so many microbial genes that, using a large number of markers, one could even identify a specific person. The microbiome is like a fingerprint.

And how do we acquire these microbes? Most, at birth. Although it is true that there is much debate about whether the placenta also contains microbes, if there are any, there would be very few, so the first major exposure occurs when passing through the mother's canal, which puts us in contact with the microbes of vaginal fluid, blood, feces and, later, also of the skin. A massive colonization of microbes then occurs which, when they reach the intestine, generate a very powerful stimulus that activates the intestinal immune cells. This initial stimulus is fundamental for our immune system to develop and be powerful yet balanced. During the rest of our lives, the bacteria in our intestine constantly train this system, keep it awake and, at the same time, teach it to differentiate which cells are our own and should not be attacked, and which cells are pathogens that must be kept under control.

What discoveries has the study of the microbiome led to? We are still learning how it works and seeing the links between some of its functions and certain diseases. It has only been 10 years since we have really been able to accurately characterize bacteria. Right now, we are trying to simplify everything with two objectives. On the one hand, to develop a tool to distinguish which patients might respond better or worse to specific drugs and which might have more or less risk of developing certain diseases. And, on the other hand, we want to intervene on this microbiome to, as I said before, be able to modulate it: curb the bacteria we don't like as much and boost the ones we like more. It is a complex area of work that could start to yield results in about 15 years.

What concrete effects can this have on cancer treatment? One of the great revolutions of recent years in this field has been treatments capable of modifying the immune system, of stimulating it so that it can detect cancer cells and eliminate them. And what is being seen is that the presence of certain bacteria can make us respond better to these immunotherapies. At the same time, it is being seen that often people who do not respond as well to them have a different or weakened microbiome composition due to taking antibiotics massively during treatment. In studies with mice, it has been found that when we supplement them with the relevant bacteria, the animals begin to respond. So we have very promising signs. Now the challenge is to see how we go from rodent to human, and what we can do specifically to ensure a better response to immunotherapies.

Is it the same with AIDS? At IrsiCaixa, we are interested in the microbiome because, among our HIV patients, those with more alterations in the microbiome are also those with the most deteriorated immune system. What we want is, first, to help them strengthen this system so that they have fewer complications and, second, to improve the response to the vaccines we are developing to, one day, be able to cure AIDS.

We can be grateful to microbes! In fact, it has also been observed that there are changes in the microbiome associated with the development of autoimmune diseases such as multiple sclerosis. It could even be used to reduce allergies. The goal is always to achieve a balanced microbiome. I truly believe that this is a very interesting time for medicine and that, to a certain extent, the study of microorganisms will impact the medicine of the future.

Photography: Clara de Ramon

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