The human body is home to many microorganisms. Only now are we beginning to learn how important they are.
The more scientists investigate the microbes that live in the human body, the more they learn about the powerful influence of these crumbs on our appearance, behavior, even on the way of thinking and feeling. Are our health and wellness really dependent on viruses, bacteria, unicellular fungi and other organisms living in the lungs and intestines, on the skin and eyeballs? Isn't it too strange to believe that the microscopic creatures that we carry in ourselves and on ourselves largely determine our very essence?
The influence of the microbiome - this is the name of this mini-zoo - may be fundamental already in the early stages of development.
One of the studies, the results of which were published last year, shows that even a seemingly innate quality like an infant's temperament can depend on whether the majority of bacteria in its intestines belong to the same genus: the more bifidobacteria, the more cheerful child.
The conclusions drawn by Anna-Katariina Aatsinki and her colleagues at the University of Turku in Finland are based on the analysis of stool samples from 301 babies. Those children who had more bifidobacteria at two months were more likely to show "positive emotions" at six months, as the researchers defined.
The study of the microbiome began relatively recently - in fact, only 15 years ago. This means that most of the studies conducted to date have been preliminary and modest in scope, involving only dozens of mice or humans. Scientists have found a definite relationship between the state of the microbiome and various diseases, but they still cannot identify clear causal relationships between specific inhabitants of a densely populated "inner world" of a person and his health.
The diversity of the gut microbiome is at its best in this specimen. Among other things, we see a huge bacterium here - it is 50 times longer than E. coli. Each person's microbiome is unique. Scientists continue to explore the many ways in which the microorganisms that make up it affect our health, weight, mood and even personality traits.
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Even the number of these inhabitants is amazing: today it is believed that about 38 quintillion (10 to the power of 12) microbes live in the body of an ordinary young man - this is even more than their own human cells. If we learn to understand how to dispose of this - our own - wealth, fascinating prospects will open before us.
According to optimists, in the near future it will become common to inject a person with healthy complexes of microbes in the form of prebiotics (compounds that act as a substrate on which beneficial bacteria can multiply), probiotics (these bacteria themselves) or by fecal transplantation (transplantation of a rich intestinal microbiome from donors) - so that he can feel healthy.
When people talk about the microbiome, they primarily mean the inhabitants of the gastrointestinal tract, which make up 90 percent of our microorganisms. However, other organs are teeming with life: microbes fill any part of the body that comes into contact with the outside world: eyes, ears, nose, mouth, anus, genitourinary system. In addition, germs are present on any piece of skin, especially in the armpits, perineum, between the toes and in the navel.
The bacteria shown here are taken from sweaty feet. It is they who give the secretions of the sweat glands a peculiar smell: as it accumulates, sweat becomes a medium for the reproduction of odorous microbes. And most of the sweat glands are concentrated on our palms and soles.
And here's what's really amazing: each of us has a unique set of microbes that is not found in anyone else. Today, according to Rob Knight of the Center for Microbiome Innovation at the University of California (San Diego), it can already be argued that the probability of two people with the same set of species in microbiomes is approaching zero. The uniqueness of the microbiome could be exploited in forensic science, Knight said. "Whoever touched an object is tracked by the microbiome 'fingerprint' that is left by the human skin," he explains. Well, one day, investigators, looking for evidence, will start collecting samples of microbes living on the skin, much like they are looking for fingerprints today.
In this article, we will share some of the significant discoveries made by scientists studying the microbiome and its impact on us from infancy to old age.
Infancy
The fetus in the womb is practically sterile. Squeezing through the birth canal, he meets a myriad of bacteria. During normal childbirth, the baby is "washed" by the microbes that live in the vagina; in addition, the intestinal bacteria of the mother get on it. These microbes immediately begin to inhabit its own intestines, entering into a kind of communication with the developing immune system. Thus, even in the earliest stages of its existence, the microbiome prepares the immune system to function properly in the future.
If the baby is born through a caesarean section, there is no contact with the mother's bacteria, and other microorganisms colonize his intestines - from the mother's skin and from breast milk, from the nurse's hands, even from hospital linen. Such a foreign microbiome can complicate a person's entire future life.
Streptococcus pneumoniae, shown here at the time of cell division, can cause serious illnesses such as meningitis and pneumonia - however, like strains of E. coli, some streptococci are harmless. These bacteria live on the skin and mouth, in the respiratory tract and in the intestines.
In 2018, Paul Wilms from the Center for Systems Medicine at the University of Luxembourg published the results of a study of 13 naturally born babies and 18 surgically born babies. Wilms and colleagues analyzed the stool of newborns and their mothers, as well as vaginal swabs of women in labor. The "Caesareans" had significantly fewer bacteria that produce lipopolysaccharides and thereby stimulate the development of the immune system. There are few such microbes left for at least five days after birth - this, according to Wilms, is enough to lead to long-term consequences for immunity.
After some time, usually by the first birthday, the microbiomes of children in both groups acquire similarities. However, according to Wilms, the difference observed in the early days of life means that in the body of babies born by caesarean section, primary immunization may not go through, during which immune cells learn to respond correctly to external influences. This probably explains why these children are more likely to experience a variety of problems associated with the functioning of the immune system, including allergies, inflammation and obesity. According to Wilms, in the future, perhaps, "Caesareans" will be given probiotics created on the basis of strains of the mother's bacteria in order to populate their digestive system with beneficial microbes.
Childhood
Food allergies have become so common that some schools have imposed restrictions on the food that children can take with them from home (for example, they are not allowed to bring peanut bars or jam sandwiches) so that some classmates do not develop allergies. reaction. In the United States, 5.6 million children suffer from food allergies, which means there are at least two to three such children in every class.
A variety of reasons are cited that could lead to the spread of allergies, including an increase in the number of children born by caesarean section, and the overuse of antibiotics that can destroy the bacteria that protect us. Katherine Nagler and her colleagues at the University of Chicago decided to test whether the spread of food allergies among children is related to the composition of their microbiome. Last year, they published the results of a study that involved eight six-month-olds, half of whom were allergic to cow's milk. It turned out that the microbiomes in the two groups were quite different: in the intestines of healthy babies there were bacteria typical for properly developing children of their age, while those suffering from cow's milk allergy showed bacteria more typical of adults.
In children with allergies, Nagler says, the usually slow transition from childhood to adult microbiome "occurred at an abnormal rate."
Nagler and her colleagues transplanted (using fecal transplants) the intestinal bacteria of “their” babies into mice born by Caesarean section and raised under sterile conditions, that is, completely free of microbes. It turned out that only mice transplanted from healthy babies did not show an allergic reaction to cow's milk. Others, like their donors, have become allergic.
Further studies showed that the main role in the protection of the first group of mice, apparently, was played by bacteria of one species, found only in children: Anaerostipes caccae from the group of Clostridia. Clostridia also prevents peanut allergies, Nagler and her colleagues found in one study.
Nagler, president and co-founder of the Chicago-based pharmaceutical startup ClostraBio, expects to test the therapeutic potential of Anaerostipes caccae bacteria in laboratory mice and then in allergic people. The first task was to find a place in the intestines where a troop of beneficial bacteria could be landed. Even in an unhealthy microbiome, Nagler says, all niches are already filled; so that in order for Clostridia to take root in a new place, you need to drive out the previous inhabitants. Therefore, ClostraBio has created a drug that clears a certain niche in the microbiome. Nagler and his colleagues "prescribe" it to mice, and then inject them with several types of Clostridia, as well as dietary fiber that promotes the reproduction of microbes. Nagler hopes to begin human clinical trials of Clostridia within the next two years.and eventually, to create a medicine for children with food allergies.
Gut microbes can be linked to other diseases in children, including type I diabetes. In Australia, scientists analyzed stool samples from 93 children whose relatives suffered from diabetes, and found that those of them who subsequently developed the disease had an increased content of enterovirus A in their feces. However, one of the experimenters, W. Ian Lipkin from Meilmanovskaya School of Public Health at Columbia University, warns colleagues against hasty conclusions that the causes of certain diseases are due solely to differences in the microbiome. “All we know for sure,” he says, “is that certain microbes are somehow linked to certain diseases.”
Still, Lipkin is enthusiastic about the future of microbiome science. According to his forecast, within the next fifty years, scientists will reveal the mechanism of the microbiome's effect on the body and begin clinical trials in humans in order to demonstrate how health can be improved by “editing” the microbiome.
Youth
Many adolescents have a predisposition to acne - and there seems to be a phenomenon called the "sebaceous microbiome." The guys' skin is particularly welcoming to two strains of the Cutibacterium acnes bacteria associated with acne. Most strains of this bacterium are safe or even beneficial because they inhibit the growth of pathogenic microbes; in fact, this bacterium is a major component of the normal face and neck microbiome.
However, a bad strain can do a lot of harm: its presence, according to Amanda Nelson, a dermatologist at the Pennsylvania State University College of Medicine, is one of the prerequisites for the development of inflammation. Among other causes of the disease, scientists cite sebum (produced by the sebaceous glands to moisturize the skin), which serves as a breeding ground for C. acnes, hair follicles and a tendency to inflammation. It all works together, and according to Nelson, we don't yet know which is more important.
The microbiome of the sebaceous glands was studied by scientists at the University of Washington School of Medicine and found that the only anti-acne agent that can lead to long-term weakening of the disease, isotretinoin (known by various trade names), works in part by altering the skin microbiome, increasing the overall diversity of microbes, among which are more difficult for harmful strains to take root.
Now that scientists have learned that isotretinoin works by altering the composition of the microbiome, they may try to create other drugs with the same effect, but they hope are safer - after all, isotretinoin can lead to birth defects in children if mothers took the drug during during pregnancy.
All sorts of germs have taken a liking to wet lips. This is the microbiome of one of the women who literally kissed a petri dish with a nutrient medium. In a few days, the colony was already flourishing. In people who often kiss each other, there are similarities between the mycobiomes of the oral cavity.
Maturity
What if you can do more with your workouts by simply borrowing an athlete's gut microbes? This question was asked by scientists from Harvard University. For two weeks, they collected daily stool samples from 15 runners who took part in the 2015 Boston Marathon - starting a week before the race and finishing a week later - and compared them to stool samples collected from ten people in the control group also over two weeks. not running. The researchers found that a few days after the marathon, the samples taken from the runners contained significantly more Veillonella atypica bacteria than those from the control group.
“This discovery explains a lot, because Veilonella has a unique metabolism: her favorite energy source is lactate, the salt of lactic acid,” says Aleksandar Kostić of the Joslin Diabetes Research Center and Harvard Medical School. - And we thought: maybe Veilonella decomposes muscle lactate in the athlete's body? And, if this is really so, is it possible, by introducing its strains to people far from professional sports, to increase their endurance?
Then the scientists turned to laboratory mice: Veilonella isolated from the stool of one of the runners was injected into 16 mice with a normal microbiome tested for pathogens. Subjects were then placed on a treadmill and forced to run until exhausted. The same was done with 16 control mice; only they were injected with bacteria that do not consume lactate. As it turned out, the mice "infected" with Veilonella ran much longer than the control animals, which means, the researchers believe, the microbiome can play a critical role in maintaining performance.
According to Kostich, this experiment is "a wonderful example of what symbiosis gives us." Veilonella thrives when a person, its carrier, as a result of physical activity produces lactate, which she feeds on, and, in turn, benefits the person by converting lactate into propionate, which affects the performance of the host, because, among other things, increases the frequency contractions of the heart and improves oxygen metabolism, and also, possibly, prevents the development of inflammation in the muscles.
“This kind of relationship seems to underlie most of the interactions between humans and the microbiome,” explains Kostich. "Ultimately, the relationship between them is so mutually beneficial."
The microbiome may be responsible for the less pleasing features of human nature, including mental conditions such as anxiety and depression. In 2016, scientists from the National University of Ireland in Cork published their findings on the microbiome's impact on depression. The researchers divided 28 laboratory rats into two groups. The experimental group received transplants of intestinal microflora from three men suffering from severe depression, and the control group - from three healthy men.
It turned out that the gut microbiome of depressed people plunged into depression and rats. Compared with control animals, they showed a loss of interest in activities that bring pleasure (in rats this is determined by how often they want to drink sweet water), and increased anxiety, expressed in their desire to avoid open or unfamiliar areas of the laboratory maze.
Given the big difference between rats and humans, the scientists note that their study is new evidence that the gut microbiome may play a role in the development of depression. Sooner or later, they say, the day may come when depression and other similar disorders will be fought, including by targeting certain bacteria in the human body.
Old age
The microbiome is both resilient and fluid at the same time. Its unique structure is largely formed by the age of four, and only very significant factors can really affect it - for example, a change in diet, the intensity of physical activity or time spent in the fresh air, moving to a new place of residence, the use of antibiotics and some other medicines. However, in a sense, the microbiome is in constant flux, changing subtly with each meal. In adults, these changes are so predictable that your age can be roughly determined by just familiarizing yourself with the set of bacteria living in the intestines.
This technique, known as "determining age by the microbiome aging clock," requires the assistance of artificial intelligence, such as in an experiment recently conducted by Hong Kong-based startup Insilico Medicine. Scientists have collected information on the microbiomes of 1165 people from Europe, Asia and North America. One third of them were 20-30 years old, another third - 40-50, and the last - 60-90 years old.
Scientists, by marking the age of their carriers, subjected the data on 90 percent of microbiomes to “computer interpretation”, and then applied the patterns identified by artificial intelligence to the microbiomes of the remaining ten percent of people whose age was not marked. Their age was established with an error of only four years.
What does it mean to “edit” your microbiome and live in peace? Alas, even the biggest microbiome science enthusiasts say that it is difficult to draw accurate conclusions about the relationship between the microbiome and human health so far, and insist that great care must be taken in the transition to treatment with bacterial grafts.
Many are now raving about the potential for microbiota to be used as a medicine, says Paul Wilms of the University of Luxembourg, noting that pharmaceutical companies are developing new probiotics that aim to balance the microbiome.
“Before we can do it really right and intelligently,” says Wilms, “we need to understand in detail what a healthy microbiome is and how it affects the human body. I think we are still very far from that."
Microbes inside us
- colon - 38 quintillion
- plaque - 1 quintillion
- skin - 180 billion
- saliva - 100 billion
- small intestine - 40 billion
- stomach - 9 million
* approximate amount
See the microbiome
All the images in this article were taken by Martin Eggerly using a scanning electron microscope: the samples were dried, gold atoms were sprayed on them and placed in a vacuum chamber. The wavelength of the electron beam of the microscope is shorter than the visible light, so the beam "highlights" the smallest objects, but outside the color spectrum. Eggerly dyed microbes, the color of which is known, in these colors, in other cases he chose a different gamut so that microbes and their characteristic features could be distinguished.
Text: Robin Marantz Hoenig; Photo: Martin Eggerly