Recently, the journal Nature published another article that blames a number of human diseases, including mental ones, on microbes - the inhabitants of our intestines. For half a century of studying intestinal bacteria, scientists have not been able to determine what they bring more - benefit or harm. But we managed to make sure that, among other things, microbes can cause changes in human behavior and mental health. We translate their signals from microbial language into human language and invite the reader to decide for himself whether bacteria are friends or enemies (but we do not promise that they will not affect his opinion).
About microbes and people
Remember the Soviet cartoon about an elk, on whose horns forest animals rode and made a house there? Our body is the same elk for trillions of single-celled organisms (most of them bacteria), which are collectively called microbes, microflora or microbiota. You can even say that we and our microbes constitute one meta-organism, which must be considered as a whole, since there are no people without microbes.
Humans and microbes have united in the name of the most valuable thing a living organism needs - food. People know how to get it, and microbes can digest it. However, for peaceful coexistence, they need to fulfill the non-aggression pact. Therefore, by acting on the accumulation of immune cells in the intestinal wall, bacteria mitigate the possible immune response. If this does not happen, for example, due to a lack of bacteria, the person's immunity becomes more aggressive. Probably, it is because of this that children who grow up in conditions of a low bacterial content (clean, out of contact with the mother and her milk) are more likely to develop allergies and autoimmune diseases. For their part, microbes do not destroy the intestinal wall. However, they remain peaceful neighbors only until they penetrate into the human body. There they cause severe inflammation,which are not easy to deal with.
In addition, microbes require protection of their interests. For example, it is important for them that they regularly receive food, and that the intestinal wall does not injure them. To do this, they release signaling molecules that regulate the activity of the surrounding host cells, for example, the absorption or secretion of enzymes, or even the deposition of fat (yes, there is evidence that obesity is associated with an imbalance in the intestinal microbiota). And, finally, such coexistence sometimes leads to strange effects. For example, microbes can ingest or modify drugs taken by the host, which sometimes significantly reduces the effectiveness of treatment. Or they can secrete their DNA (as part of gene exchange with other bacteria), which may be absorbed by the surrounding host tissues. So far, there is no unequivocal evidence that bacterial genes work in the cells of the intestinal wall. However, similar cases are known in insects and worms. And in the human genome, some sequences were found that are suspiciously similar to bacterial ones. Probably, there is a little more in common between us and our micro-inhabitants than it seems at first glance.
What are microbes doing in the human body? Illustration: Mikhail Fomin, Attic.
It turns out, on the one hand, that danger is always near. On the other hand, it is impossible to get rid of it, because the absence of microbes turns into even worse consequences than their presence. So, for example, according to the "hygienic hypothesis", excessive striving for cleanliness and hygiene is harmful to health, and early contact of a child with bacteria and allergens, on the contrary, strengthens the immune system. However, articles are still being published whose authors consider microbes as parasites that use humans for their own needs. And here the influence of microbiota on the human nervous system becomes a strong argument.
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The path to the brain through the stomach
It would seem, where is the brain, and where is the stomach? Nevertheless, the first thing the body needs to survive is food, which means that the brain must clearly understand whether it is there, what is happening to it and whether the digestive system is working well. Especially for this, enterochromaffin cells are located in the intestinal wall - microglands, which secrete many regulatory substances. Some of them act on nearby cells, stimulating or slowing down digestion. Others activate neurons in the intestinal wall, in particular the end of the vagus nerve, which goes directly to the brain. In addition, painful endings are found under the surface of the intestine, which also respond to substances secreted by enterochromaffin cells, and can signal that the body has eaten something wrong. Finally, the intestinal wall is populated with immune cells,sensitive to penetrating substances. When an enemy is detected, these cells trigger inflammation, while substances are released that act on the nerve endings and enter the bloodstream. Thus, stress can go from local to global.
Of course, information about the activity of bacteria also quickly appears in the brain. Firstly, "peaceful" microbes stimulate digestion, and many of the foods they digest or synthesize enter the bloodstream. For example, short-chain fatty acids (by breaking down which, we get 5-10% of our daily energy). The brain cells have receptors that catch them and signal a feeling of satiety. In addition, the brain develops better with energy resources. Schizophrenia and bipolar disorder are more common in children who are undernourished in the womb. An increase in the amount of short-chain fatty acids in the blood, on the contrary, stimulates learning and memory.
Secondly, bacteria actively communicate with the intestinal wall (and through it - with the host's brain), releasing substances that act on enterochromaffin cells. Interestingly, the signaling substances of bacteria are simply direct analogs of our own hormones and neurotransmitters: it turned out that the intestinal microflora can produce norepinephrine, dopamine, serotonin, testosterone, histamine, as well as the neurotransmitter gamma-aminobutyric acid and proteins - appetite regulators (for example, ghrelin and leptin). Moreover, some bacteria can secrete benzodiazepines - substances that have a calming effect (among their relatives, for example, the famous tranquilizer phenazepam). Scientists believe that all of these signaling molecules are very ancient and were used by bacteria to communicate with each other back in those days.when multicellular organisms were just evolving. That is, the intestinal microflora acts as an additional iron in the human body.
Illustration: Mikhail Fomin, Attic.
So what do microbes want?
In a first approximation, the motivation of microbes is not difficult: they want food. If there are not enough nutrients for them, then they can secrete substances that stimulate painful endings in the intestinal wall. There is even a frightening hypothesis that colic in babies is also caused by bacteria: pain causes the body to redirect internal energy resources to the intestinal area, and crying (caused by the action of microbes on the brain) attracts parents who try to feed the baby in order to calm it down.
If the owner is old enough, then it is possible to regulate his food production directly through his nervous system. For example, given enough food, some of our beneficial neighbors synthesize the essential amino acid tryptophan, which is the basis for our body's production of serotonin, the so-called "happiness hormone." Serotonin, in turn, regulates the activity of the nervous system, causing feelings of satiety, calmness and joy. With a lack of food, microbial hormones and a neurotransmitter can shift behavior towards anxiety and exploratory behavior. In a famous experiment, scientists transplanted microflora from a line of mice with increased anxiety to normal mice, and their level of anxiety also increased. Features of the microbiota have also been found in people with behavioral disorders, such as those suffering from depression, schizophrenia and anorexia. Scientists believe that neurotransmitter imbalances caused by gut bacteria may be the cause of these disorders.
Plus, germs crave their favorite food. The microbiota is made up of many types of bacteria that differ in their food preferences. And each type of bacteria seeks to act on the host's body in such a way that it often eats precisely their favorite substances. This is probably why the composition of the intestinal microflora also differs in people who adhere to different dietary regimes: the dominant microbes cause cravings for different types of food. They can achieve this, for example, by redistributing taste buds. It is known that the sense of taste can change during operations on the intestines, during which the microbial composition inevitably changes. But even in those who follow the same diet, bacteria can cause a shift in food preferences. Scientists have compared the content of bacterial substances in the urine of sweets and people who are indifferent to sweets,who nevertheless ate the same. It turned out that these substances in the urine are different! It turns out that the craving for sugar may be a property of the microflora, and not of its owner. So if it seems to you that you are pathologically in love with chocolate, then it is possible that your microbes actually adore it.
Finally, microbes want to travel, enter other organisms, and exchange genes with distant relatives living with other hosts. Therefore, it would be beneficial for them to increase the sociality of a person. Indeed, it has been found that mice raised in a germ-free environment exhibit behaviors similar to those of autistic people, because they do not receive an internal socializing signal. Also, scientists have identified differences in the microbiota of children with autism spectrum disorders from healthy children. However, most autistic children limit their diet to a small set of foods. It is believed that this is due to the imbalance of their microflora: some microbes are many, others are almost none, therefore taste preferences are strongly biased, and there are not enough calls for sociality from bacteria.
Contagious appetite
So, many behavioral traits or disorders can be bacterial in nature. This leads to two conclusions that are likely to influence the medicine of the future.
1) Behavioral traits can be transmitted by microbes.
This is supported by an experiment with mice, in which the transplantation of microflora changed their behavior towards more alarming. In addition, scientists have calculated that people with close acquaintances who are obese are at increased risk of developing the same symptom. It is possible that the propensity to obesity can also be transmitted along with microbes, although this has not yet been directly proven. Finally, there is a hypothesis that taste preferences (which, as we already know, can also change under the influence of bacteria) are closer in members of the same family than in unfamiliar people. This probably makes it possible to reveal the "secret of mother's borscht" - food prepared at home may seem tastier than others, not only because a person gets used to it from childhood, but also because his relatives have the closest composition of bacteria to him,which require the same nutrients.
2) Behavioral features can be treated with microbes.
More and more diseases appear to be associated with differences in the gut microbiota. For example, recently, scientists in 100% of cases were able to distinguish between people suffering from depression and healthy people using only stool analysis. And when the cause becomes known, opportunities for treatment open up. And despite the fact that generally available microbial therapy has not yet been developed, isolated studies show amazing results. For example, the same depression could be cured more successfully when antidepressants were combined with antibiotics (destroying excess intestinal inhabitants). And fecal transplants (complex procedures in which bacteria are removed from the stool of healthy people, packed in capsules and fed to patients with them) have reduced the severity of autism symptoms in humans. Finally, microbial prevention has also borne fruit: among a group of children,who were regularly fed probiotics (that is, a set of microbes from "normal" microflora), no one developed either Asperger's or Attention Deficit Hyperactivity Disorder, while in the control group 17% of children grew up with one of these behavioral abnormalities.
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The latest news from the lives of our intestinal neighbors make us reconsider our outlook on life. Much of what was previously considered an inalienable (and sometimes incurable) property of the human body turns out to be the result of microbial imbalance. You involuntarily wonder: where is the real person, not subject to these microscopic manipulators? In the meantime, scientists are looking for a way to negotiate with them, it is recommended not to panic and drink kefir: studies have shown that lactic acid bacteria not only improve digestion, but also cheer up, and it becomes more fun to wait for the next discoveries.