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You think about yourself as a unique individual, you experience yourself and your body as a whole. You have one name, but you should actually have many names. You are not one, you are an exuberant ever-changing crowd, a planet swarming with life, a symbiotic microbiome full of millions of micro-organisms that perform various, indispensable functions in your body. In fact, you are innumerable, always a ‘we’ and never merely an ‘I’.
Our bodies probably contain more cells of microbial than primate origin. These microbes don’t just live on our bodies, like moss on a tree in a host-symbiont kind of way, but are rather an integral (and hereditary) part of us, without which we wouldn’t be ourselves. Moreover, without them we’d get sick or might even die.
These microbial communities aren’t static over time either, but ever-changing throughout your life from the moment you are born through exchange with the microbiomes of others, with whom you are connected in a so-called pan-microbiom.1As an ecological community of organisms myself I (or should I say ‘we’?) explore the implications for our understanding of ‘self’ and how we relate to the ‘other’ – of similar and of different species and even domains of life – and how this could disrupt our world views, our politics and our health care systems.
i The myth of individuality
Where we discover biological individuality is not a real thing.
The discovery of the microbiome, and the fact that you are basically multiple-organisms-in-one, might have profound implications for our sense of “self”, especially our sense of individuality. Therefore, I will first touch upon how the individuality takes shape in our daily lives, before explaining more about what the microbiome really is and how it operates.
Our individuality is very much a part of how we see ourselves and have shaped our societies. It is a key asset in the Western world: we have the right to self-determination and we also believe that we have the right to fulfill our personal needs and pursue our dreams. Most countries’ legal systems hold people individually responsible for their actions. Conviction as a group is not possible without individual involvement of each person having been proved. Another example to illustrate that individuality is implicitly the norm is our healthcare system. When you are ill, you go to the doctor, who examines your body and prescribes a treatment. Unless you have a holistic doctor, or unless your illness has to do with your intestines, it is unlikely that your microbiome is considered at all. Physicians might consider the body in a holistic and interconnected way, but nonetheless the body is the unit to be treated. At most, the disease record of the immediate family is asked, but the bodies of the people in your life are not considered part of the treatment.
As it turns out, they should be. When we get sick, our bodies are no isolated units that can be treated in isolation. We are continuously in connection with other organisms, within ourselves and from without – of our own and different species. We exchange microbial cells with whomever we meet. This helps spread disease, such as the current COVID-19 pandemic. But can the connections between humans and their microbiomes also provide a clue to stay healthy, cure disease, or even prevent it?
To put the microbiome in perspective, let’s go way, way back to the beginning of life on planet Earth to see how life with its extraordinary richness of species came about and how even as organisms diverge into separate species and sperate domains, somehow they tend to always end up together again.
ii From one to millions in a couple of billion years
Where we learn we have been merged with “the other” twice already.
For most of the existence of planet Earth, only single-celled organisms crawled over its surface. We multicellular organisms are a relatively young development. The very first single-celled lifeforms originated about 3.5 billion years ago and were divided into two life domains: bacteria and archaea.
The third and final domain of eukarya entered the stage in a rather peculiar way. Eukarya are the result of a bacterium that started to colonize archaea, living inside them, and eventually becoming an indispensable, hereditary part of them. Due to the extra energy source of the mitochondrion (a former bacteria), eukaryotes were able to grow beyond the single celled state to ever larger multicellular organisms. They now form a motley variety on earth, from lemur to carnivorous fungus, to redwood trees and flying ants. And humans.
These are the three major domains of life on Earth: Bacteria, Archaea and Eukaryote. Every living organism belongs to one of these three domains. However, the question is whether this separation is genuinely so absolute, when you consider that the majority of “your” cells today are of microbiotic origin. Basically, we have been colonized all over again. You may find that a particularly dirty thought, bacteria crawling all over (and inside) you by the millions, maybe even outnumbering your own cells. 2
Although they exist billions of years longer than we do, we only discovered bacteria in the 19th century, thanks to the chemist Louis Pasteur, who discovered that they cause diseases such as tuberculosis and cholera. We use antibiotics and antibacterial cleaners to keep these tiny pathogens out of our bodies.
Although you may associate bacteria with “sick” and “bad” – just like viruses, which we will return to later – only a few hundred types of bacteria actually are pathogenic. Thousands of species are harmless, and many are even necessary for survival. In any case, we see micro-organisms as a different species, belonging to a completely different domain than ourselves. Obvious, right?
Not really, it turns out. Soon after Pasteur’s discovery, Australian pediatrician Theodor Escherich observed that the bacterium Escheria coli is a critical part of the gut flora in healthy children. Since then it has come to light that our bodies contain communities of micro-organisms, the microbiome, roaming our bodies as nomad communities exploring our surface and interior cavities. In addition to bacteria, the microbiome also contains viruses, fungi and protozoa and fulfills countless, indispensable functions in brain development, the immune system and even our social life, as I will show later.
The big question is: Are you a human being on which microbes live, or are you a microbiome that contains a human being? Or can it no longer be determined where human ends and microbiome begins?
iii Where does the microbiome end and the ‘you’ in yourself begin?
Where we learn, there is no clear distinction.
From the moment you are born, you cease to be an individual. Babies in the womb are sterile, but when they are born naturally through the vagina, they are swiftly colonized by their mother’s microbiome. You could say that you inherit not only the genetic material from your Homo sapiens parents, but also the genetic material of your mother’s microbiotic ecosystems. Breast milk mostly isn’t even meant for the baby itself but feeds the first microbes of a baby 3. These first microbes build species-rich communities in the intestines, thereby giving the baby the go-ahead for the construction of a unique microbiome of its own, which may eventually exceed the ‘own’ cells in numbers of cells.
Does it still make sense to talk about “our” cells’ and “other” cells? One way to distinguish between human and microbiome is to look at the genes: Which are theirs and which are mine? Amazingly, the genes of some of our microbe inhabitants code for crucial human traits we didn’t have lest we evolved for ourselves, such as the ability to digest food, develop brain, bones, an endocrine system and intestines – to name a few. Actually, microbes contribute more gene functions than our “own” genome4. These microbe genes are inherited as we saw above. Not just vertically, from our birth mothers, but also horizontally, between people you meet on a daily basis 5. – well, before the COVID-19 pandemic anyway.
So, genetically it’s difficult to make a strict division between ourselves and the others. We can also enlist the help of the immune system to make this distinction. After all, the immune system is our signal against external invaders, and is thus designed to recognize “our” cells and “other” cells. But we would over-simplify matters if we consider the immune system a means to distinguish self from non-self, when in fact, it distinguishes bad self (cancer) and bad non-self (pathogens) from good self (healthy cells) and good non-self (microbiome)6. Our immune system doesn’t snuff out microbial cells that are part of the microbiome like it does to pathogen microbes. In fact, we need the microbiome to develop our immune system at all.
You can say we are very intimately intertwined with our microbiome. Some of the things that define our individual selves such as self-awareness, personality traits and emotional state are at least partially controlled by microbes7. Who you like and fall in love with for instance. Pheromones give you your unique scent and determine who you are attracted to. It is bacteria on your skin that secrete these pheromones and influence our choice of partner. Gut bacteria Lactobacillus and Bifidobacterium also manipulate our social behavior and can influence whether we feel anxious or even depressed. Animal studies have linked the gut’s bacterial makeup to risk-taking behavior, anxiety, stress, sexual preferences and bonding8.
Microbes do not operate unilaterally, they are in constant contact with our brain through the vagus nerve (a large nerve that connects the gut to the brain), the immune system, hormones and the production of neuroactive substances by gut microbes. Brain and microbes constantly signal to and influence each other. Stress (both physical and mental) can affect the composition and activity of the gut microbiota, just like changes to the gut microbiome can affect emotional behavior and related brain systems.9. So, there is no clear distinction between human host and microbiome, we can’t really tell where one ends and the other begins. You are like a planet that hosts a wild variety of microbial ecosystems. Try and remove the ecosystems, you take out the life of the planet and end up with a dead, orbiting rock. Although it is not clear we couldn’t survive without our microbes, scientists aren’t sure what kind of life it would be10.
iv You are an abundant planet
Where we learn what it means to be covered by vast ecosystems.
I quite like the analogy of the life supporting planet. Just like a planet where different ecosystems flourish under different conditions (temperature, climate, longitude) our bodies grow different ecosystems on different locations. The desert of the skin hosts different communities than the oceans in our eyes or the dense and species-rich rainforest of the gut.
The effect of microbes on us depends on the location where they appear and reside, but also whether the communities in that location are in balance. A healthy microbiotic ecosystem can easily deal with harmful invaders. A healthy microbiotic gut community responds to pathogens by producing antimicrobial proteins and is a line of defense. An imbalanced ecosystem on the other hand, like a robbed rainforest, is very susceptible to outside influences. For example, people that had an antibiotic treatment decimate not only the pathogens, but also millions of helpful gut microbes that help digest food and build the immune system. It takes a long time for benevolent bacteria to recolonize the gut. The species diversity after the treatment is much lower than before and often isn’t fully restored11. While the microbial gut ecosystem is still rebuilding, the body has a harder time fighting off pathogens.
Another reason I think the planet metaphor is apt, is the fact that a planet doesn’t exist in isolation. It is part of a larger cosmos. It rotates around a sun in a solar system with other planets, in a galaxy full of stars and planets, many of which are purportedly habitable. And unlike human astronauts who still have to discover their first extraterrestrial life form, the planet “me” is rotating around other planets and sending microbial astronauts and receiving bacterial aliens on a daily basis.
v Implications of the pan-microbiome
Where we learn that taking antibiotics might be a social act.
Our health care is focused on individual health, with little attention to the consequences for public health. This is a missed opportunity given the shared nature of the human microbiome, the pan-microbiome, across communities, and vertical and horizontal mechanisms for the exchange of microbiomes between humans.
Our microbiotic ecosystems are not static but are continuously exchanging information and cells with other systems. The way we move through the world and turn around each other, we exchange entire communities of our unique ecosystems with whoever we meet. We leave our microbes with every handshake, every cough and even without any effort. Our microbiome extends beyond our skin,12 surrounds us like an aura, like orbiting satellites, if you will. Because of this cloud it is not even necessary to touch someone (or something) to exchange microbes. You can walk through a forest and pick up some microorganisms from the entities that inhabit it.
We are not individual, discrete organisms, but crowds, constantly changing composition with every meeting, every forest walk and every train journey.This means that something like taking antibiotics is not merely an individual act, but a social act that influences not just your body and health, but the health of those around you and even the entire pan-microbial community13. If we take antibiotics and impoverish our microbiome, this has an effect on other’s we meet. If our microbial ecosystems are species poor or house pathogens, others can pick up on that too. The opposite is also true: we could culture and transfer protective microbes to promote health and fight disease14. And it’s not unthinkable that our social connections alter our microbiome in ways that heighten immunity15.
Despite the holistic rhetoric surrounding state of the art microbiome research, big metagenome research projects like the Human Microbiome Project (HMP) still focus mostly on gene research and bypasses the complex interactions and everchanging nature of the human microbiome. It still treats the microbiome as a single unit to be studied and dissected, something you can influence and control. Some of the biggest discoveries of the HMP are used to create antibiotics16. What if we think and act bigger, quite literally?
vi Disease and the microbiome
Where we realize we can’t ignore the microbiome when dealing with a pandemic.
As mentioned, an imbalance in the human microbiome makes it easier for pathogens to colonize the body and disease to cause havoc. Dysbiosis, as this is called, in the gut microbiome has been associated with obesity, inflammatory bowel disease, diabetes and metabolic syndrome18. Much less antibiotics are prescribed in Germany and the Netherlands. Is this a clue for handling this and possible future pandemics? Could it be that because of the excessive antibiotics usage, the microbiome of the average person in Italy is more imbalanced? The course of COVID-19 differs from person to person and cannot be fully predicted. Not all people get sick to the same degree. The course of COVID-19 also differs from country to country. Does the (pan-)microbiome have something to do with all this? I think it’s most arrogant to think that it doesn’t. We just don’t know how exactly and to what extent.
If we do want to learn more about how the microbiome influences the course of diseases and to what extent it influences battling harmful pathogens, it clearly is not enough to look at individual microbiomes, we must also take the pan-microbiome of the whole community into consideration. We already know lots about keeping our individual microbiomes in shape: eating a plant-based diet, foods rich in probiotics such as yoghurt, and limiting antibiotics. But how do we go about keeping the pan-microbiome in shape? Is it possible to create conditions that promote distribution of good microbiota throughout the population? Is there a more social and interconnected approach to healthcare?
Right now, we seem to be doing the opposite of enlisting the pan-microbiomes help. With social distancing, prohibition of social contacts and self-isolation as main strategies to curb COVID-19, our social life is drastically curtailed. This has a profound impact on many humans, who are inherently social organisms. Humans who live together with others are generally healthier and happier. There is an increasing body of research indicating that a diverse microbiome has something to do with frequency and quality of social interaction19. Limited social interaction may contribute to reduced diversity in gut microbial communities among older persons or the socially isolated, who as a result could become more susceptible to stress and disease.20
Babies born in China whose mothers test positive for COVID-19 are separated from their mother and cared for by people in sterile suits. Can their microbiome kick-start properly in these isolated circumstances? It is known that babies born by cesarean section already have vastly different microbiomes than babies born vaginally: communities from their mother’s skin surface, whereas babies born vaginally have communities reflecting their mother’s vaginal microbiome. Cesarean babies are more prone to disease such as respiratory infections and allergies. We don’t even know what the effect of totally isolating babies is on the microbiome and their health.21
You could say we need to act socially in order to stay healthy. Because of social distancing and quarantining, some people no longer interact physically with each other. This seems ironic in light of the aforementioned importance of social behavior for health. Still, it may be the right strategy now, but how long do we keep the social distancing measure in place and for whom? At which point do the negative consequences outweigh the positive?
vii We are indeed many and contain multitudes. Now what?
Where we ask ourselves more questions
What does this bring us? First of all, we need to revise our image of individual and static self. When we realize that we are connected from the inside with all life around us, it makes us mindful of how all life, throughout history, has always been connected. We do not exist in isolation, we are not discrete units. We are ever-changing crowds that need the exchange with other crowds to thrive.
Obviously, we are missing out on that right now. Is social distancing impoverishing our microbiome? Are we going to connect even more (literally!) with our housemates by developing similar microbiomes? Is our community’s or country’s pan-microbiome going to be less diverse after a prolonged period of self-isolation? And how does this affect our health in the future?
Answering these questions would be pure speculation, but I hope that this essay invites you to do just that. If there is one thing we realize as we are isolated in our homes, is just how much we need to be connected to “others” in the broadest sense of the term – from tiny microbe, to human companions – to stay sane and healthy. The microbiome might be the biological basis for that, but it’s a truth we’ve long experienced for ourselves.
We need tools to translate the implications of the microbiome for our human identity, health and disease and find a way to internalize this new framework. We will need scientists from fields as broad as biology, genomics, ecology, social sciences and anthropology, but we also need philosophers and artists to find a language that will go beyond scientific discoveries. The microbiome may forever change how we think about ourselves and our place in the world, very much like Galileo’s discovery that the earth is not the center of the universe, but rather – as it turned out later – just a planet, encircling a medium sized star at the edge of a galaxy.
If all this is a bit much to digest, I hope you at least take this to heart from my essay: that you realize that at this moment, and every other moment of your life, you are never, ever really alone. You are indeed many.
Marjolein Pijnappels used to study Biology but has since forgotten most and designs complex stories at Studio Lakmoes by day and explores the weird connections her brain makes by night.