Bodily Planet

text: Eliška Selinger photo: Institute of Microbiology, Czech Academy of Sciences

ACCORDING TO RECENT STUDIES, HUMAN CELLS ACCOUNT FOR ROUGHLY 47 PER CENT OF THE TOTAL NUMBER OF CELLS IN THE HUMAN BODY. 47%! THE REMAINING 53 PER CENT BELONG TO BACTERIA. THAT’S A BIG NUMBER, BUT MUCH SMALLER THAN EARLIER ESTIMATES, WHICH SUGGESTED THAT BACTERIAL CELLS ACCOUNTED FOR MORE THAN TEN TIMES THE NUMBER OF HUMAN CELLS. EVEN SO, THE LATEST FINDINGS MEAN THAT EACH PERSON HOSTS SEVERAL KILOGRAMS OF BACTERIA, WHICH IN THEMSELVES INTRODUCE BETWEEN 2 TO 20 MILLION GENES INTO THE HUMAN BODY – ABOUT A HUNDREDFOLD MORE THAN HUMAN CELLS. ALTHOUGH DISTRESSING FOR THOSE OF US WHO ARE OBSESSED WITH HYGIENE, THESE FINDINGS BRING NEW HOPE TO MILLIONS OF PEOPLE WITH AS YET INCURABLE CONDITIONS. ARMED WITH THE LATEST TECHNOLOGIES, DIETICIANS AND NEUROSCIENTISTS ARE FOCUSING THE MICROSCOPE ON THE PREVIOUSLY UNIMAGINABLE COMPLEXITY BEHIND THE WORD ‘MICROBIOME’.

Bodily Planet

It is no surprise that our digestive tract is full of bacteria. For many years scientists believed that bacteria had a commensal relationship with humans – that they lived in our gut and quietly feasted on our sustenance, but did no harm to our body nor aid it in any way. When they did let themselves be known, it was usually not much fun, and so whole generations of medical practitioners and microbiologists came to view bacteria and other microorganisms as sources of potential problems. Beginning with the work of Louis Pasteur and Robert Koch, microbes came to be viewed as a source of illness and scientific research focused on spotting potential troublemakers and uncovering how they destroy the inner environment of a host organism.

There was another parallel development in the history of microbiology, one that did not focus on the human body, but on the complex clusters of microorganisms found in our environment, particularly in soil and seawater. Environmental microbiologists quickly learnt that soil microorganisms did not live in isolation but in intricate communities, where they interacted with other microorganisms as well as surrounding inorganic substances.

With further advancements in the field of medicine, coupled with the discovery of complex communities of microorganisms in the human intestine and in other parts of the human body, medical microbiologists have embraced the ideas of their environmentally-oriented colleagues and formulated an entirely new and quite revolutionary view of the ‘planet’ known as the human body. The new perspective sees bacterial cells, as well as viral and fungal particles, as essential partners to human cells in the complex micro-ecosystem of the human body, an ecosystem marked by mutual cooperation, evolution and communication. It is a perspective that may help us to better understand microbes not only in relation to illness, but more importantly, in relation to health. From our original view of microbes as harmless and useless commensals, we have come to understand that without the human microbiome, we would not be the humans we are.

Human Microbiome Projects

The interest the human microbiome has garnered over the past two decades is nothing less than phenomenal. Around the year 2000 the number of scientific journal citations relating to our internal micro-dwellers hovered somewhere around zero; today it is in the thousands. A lot of what we know today comes from the Human Microbiome Project financed by the US National Institutes of Health, which published the results of its first phase of research in 2012. The goal of the project was to describe the microbiomes from 18 different parts of the body in as many as 242 healthy volunteers. The project confirmed the hypothesis that different parts of the body are inhabited by radically different populations, with the greatest variety found in the oral cavity and in intestinal samples. In contrast, the mucous membrane of the vagina was found to be a fairly monocultural environment populated largely by Lactobacteria. The project also

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noted fascinating differences in the microbiomes of different individuals. While all conformed to a specific human model, the individual microbiomes were so different they could easily be used in forensic science for identification purposes, just as DNA. Microbes could also tell more than we had previously thought possible. The project found, for example, that microbial composition could identify members of the same family or even reveal one’s sexual partners.

In addition to having a clearer picture of the microbiota that inhabit our body, we also now have a rough outline of the changes that happen in our microbiome over the course of our lives. The story begins well before birth, when during various phases of pregnancy the vaginal microbiome transforms under the influence of pregnancy hormones. Lactobacillus bacteria increase in their numbers, ostensibly to protect the growing embryo by occupying all available areas and keeping harmful bacteria at bay. The importance of Lactobacilli in pregnancy is further supported by a confirmed link between disturbances to this natural cycle and higher rates of preterm births. At the end of pregnancy Lactobacilli retreat, to be replaced by Proteobacteria and Actinobacteria, and the late-pregnancy microbiome is passed from the mother to the child during birth. The microbiome of a newborn child is further supported by the mother’s milk, which has evolved to contain oligosaccharides, the optimal food for the dominant microbiota in the intestines of a newborn. These oligosaccharides are not found in the milk of any other mammal. As infants transition to a solid diet, their microbiomes begin to transform into adult versions. And then, as we age, the variety of microbiota found in our internal ecosystems decline. Furthermore, the varieties and activities of the various microbiota are subject to our lifestyle choices – diet, stress, physical activity and sleep habits – and genetic predisposition. Finally, it appears that as much as we regulate our own microbiome, our individual microbiomes regulate us.

Homage to Fallen Mice

Any hypothesis about ways in which the human microbiome could be used to combat disease must first be tested on animals. One of the most popular animals for microbiome research are germ-free mice – mice that have been bred to survive a microbe-free life for as long as possible. Germ-free mice allow scientists to study how a body would evolve if it had no microbiome, and to study the effects of individual bacteria or whole populations, including those removed from human patients and transferred into mice. Studies have shown that mice that have no internal microorganisms suffer from various abnormalities, including disorders in the development of the immune system and disorders of the central nervous system. Research suggests that a significant part of the communication between intestinal microbes and the brain is carried through the vagus nerve, or the tenth cranial nerve, which regulates many functions including the heart rate and the movement of muscle tissue within the digestive tract. Treatment using several types of bacteria has resulted in an increase in the production of GABA, one of the ‘communication’ molecules of nerve cells, in certain parts of the brain. The therapy has been shown to decrease the production of stress hormones and levels of anxiety and depression.

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Yoghurt for Depression?

The compelling results from studies on mice have led to early clinical trials. Although results are still very limited, and a lot of ground remains to be covered before they can be applied in practice, the number of ailments for which microbial therapy may be relevant is growing with each step. Some of the earliest clinical trials were carried out on patients with clinical depression, which according to the World Health Organisation affects about 4.7 per cent of the world’s population. Clinical depression is characterised by changes in neural pathways, which in animal studies have been shown to be influenced by the presence – or absence – of certain microbes. Randomised studies at Tehran University of Medical Sciences in 2017 tested treatment with probiotics [specifically selected bacteria], prebiotics [substances that support the growth of suitable bacteria] and placebo in a group of more than 100 patients with clinical depression. Among the 81 patients who completed the eight-week therapy, the trial noted a significant positive effect in patients who were given the probiotic therapy, but not in patients who were given prebiotic or placebo treatments. Other clinical trials have confirmed the positive influence of probiotics even on healthy individuals – they have observed reduction in anxiety, depressive moods and levels of stress. Positive effect was also noted in people diagnosed with chronic fatigue syndrome. However, the excitement generated by these results has been tempered by findings of a Singapore-UK meta analysis from the same year, which looked at the results of more than ten randomised studies and drew the conclusion that the effects of probiotic therapy are mild and only notable in patients diagnosed with clinical depression. This study concluded that taking probiotic supplements has probably no noticeable effect in healthy individuals.

Alzheimer’s disease, Parkinson’s disease, intestinal inflammation, obesity, underweight, diabetes, autism spectrum disorder… The list of conditions, healthy and pathological, in which changes in our ‘bodily planet’ have been found to be important is long and growing. Related to this is a growing list of unresolved questions, many being the chicken-and-egg kind. Are we observing changes in a microbiome or the beginnings of an illness? What is the role of viruses and fungi, the less well-known inhabitants of our microbiome? Does the human microbiome influence other functions in our bodies? What about its influence on our ability to learn, not only in older age, but also in childhood, as some recent studies indicate? Will modern medicine be able to include targeted change to our microbiome as a method of treatment? Or will we never move beyond talking about the relationship we are unable to influence? One thing is for certain – our understanding of the human microbiome will never be as commensal, or one-sided, as it was before. ■