Research on the gut microbiome has literally exploded in the last decade. The gastrointestinal tract (GIT) was long considered only a digestive organ, but new technologies have led us to understand the impact the gut microbiome has on our health and disease. We know about its role in metabolism, the immune system, and its influence on behavior.
We also know about the changes after birth, changes that come with age throughout life, changes related to environmental characteristics, stress, health status, and administered medicines. There is a lot that we know, and certainly much more that we still do not know. (1, 2)
Living and working in our abdomen, at roughly one and a half kilograms, are around 10^14 (that is, ten to the fourteenth power) microbes, viruses, yeasts, molds, fungi, and parasites (who probably need to start being addressed more respectfully; by supplying eggs of the pig whipworm, scientists are experimentally trying to treat intestinal inflammation, asthma, and even autism), and many other tiny organisms. Their job is to help us process food and, in the process, produce a large number of enzymes that the body does not have, also to produce roughly 70–90% of various neurotransmitters and other effectors including the revered molecule serotonin, including “endozepines,” and to vigorously strengthen immunity both outwardly and inwardly and among themselves. Half the mass of our daily stool consists of these dead microorganisms, which in recent years we have been able to detect thanks to sequencing advances during studies of the human genome. That genome is already explored, and there is currently research focused on their mapping led by the National Institutes of Health (NIH) in the United States called the Human Microbiome Project.
This whole miniature zoo is called the bacteriome, or it is also known as “bacteriota,” and it has several hundred times more genes than our DNA. The dispute over whether there are ten times more of them than all cells in the body was eventually resolved in favor of our organism (so that, for example, the microbiome would not overwhelm us), because in the initial cell count red blood cells were not included in the total number. When that is corrected, we reach a much more balanced level with the microbiome. But I am not sure how microorganisms from other mucosae and surfaces including the skin will influence this.
Still, the “inner brain” (called the gut brain, or ENS)—with its own reflex activity and therefore independent of the autonomic nervous system (ANS)—has reasonably good performance, because besides what has already been said, we need to add that in the wall of the small intestine there are nerve plexuses containing the same number of neurons as the spinal cord, about one hundred million, and that the most extensive parts of the immune system are there as well. Regarding the performance of the gut brain, it does not focus on philosophy or logic, but contributes strongly to the experiences and cues of our emotional world. Here we feel “gut feelings,” sometimes called intuition.
If we also consider that what is in the gut, the intraluminal content, is actually outside the organism and that what will be absorbed from it, what will not, and what will eventually be expelled from the organism into the intestine is determined by one layer of epithelium, it is clear that its cells need strong helpers. These are components of the microbiome and the immune system. One complication can be hyperpermeability of the intestinal wall, the so-called “leaky gut,” when the spaces between individual cells, which normally are only a few angstroms wide, expand and then unwanted substances can pass into the organism, or conversely, water can leak out of the organism, as happens for example in cholera infection.
Communication with the central nervous system is ensured both through the vagus nerve, of which 90% carries information to the brain from there, and through neurotransmitters traveling in the bloodstream. To avoid there being too few revolutionary discoveries, it should also be mentioned that less than two years ago, the myth of immune isolation of the brain was disproved. Lymphatic vessels were found in the brain meninges, providing connection with the entire bodily system. (3) The whole control system is therefore much more comprehensively interconnected than we have so far imagined and much more complex.
How did we get to the gut microbiome? Long ago, far before, and that is why our tiny helpers are also called “old friends.” Colonization is a matter of evolution, and a characteristic composition of the bacteriome is found in all mammals. Howard Ochman mapped the evolution of the bacteriome of great apes and says you can comfortably follow their evolution just by following their bacteriome. The bacteriomes of two gorilla species are closer to each other than either is to the human bacteriome. Yet they retain their diversity, while this feature becomes increasingly impoverished in humans. (4) What is striking is that the panda, a bear of the bear family, feeds on leaves, consuming around 30 kg per day, and therefore has a digestive system microbiome that allows it to process and utilize this food. One can say that although it is a bear, its microbial colonization of the digestive system is more similar to that of a cow than to other bears. Humans, by contrast, have gone on a path closer to that of carnivores.
Each of us has a specific gut microbiome, relatively stable, and according to the microbiome in the mouth its composition can be estimated. And note, from the oral microbiome it is also possible to infer the risk of ICHS. The main components of the gut microbiome are bacteria of two basic types, Firmicutes (named for their firm surface—firmus + cutis) and Bacteroidetes, which together make up about 90% of the population. Among them are both “good” bacteria and potential pathobionts such as Clostridia, Helicobacer pylori, Mycobacteria, and others. Ten percent consists of a diverse mixture; the more diverse, the greater the biodiversity, the healthier it is. According to current knowledge, there is a kind of armed truce among the residents of the small and large intestine, the result of which is that none can on its own impose dominance and trigger, as a result of the ensuing imbalance, major discomfort up to manifest disease. This can, however, easily happen when dysmicrobiome occurs, i.e., when this balance is significantly disrupted by an excess of some type, more often by a lack of it. The most common cause of such a lack is the enormously used and misused antibiotics over the last fifty years and changed diet.
As it seems, even the fetus in the womb is not completely free of microbes, but there are not many of them there either. Their existence is inferred from differences in the composition of meconium depending on preterm delivery and term delivery. The newborn receives the main constituent forming the basis of the future microbiome while traveling through the birth canal from the mother—these are therefore strains contained in her vaginal microbiome, and it is highly likely that it also picks up some from her stool. This applies when the birth is conducted in the usual (vaginal) way.
In a cesarean section, this mechanism is missing, and it is therefore logical that—if birth does not take place in a strictly aseptic environment—the newborn is “endowed” with a bacterial mixture from the delivery room, which is not very advantageous, because this mixture contains all sorts of things, especially staphylococci, not to mention the more dangerous ones. The result is the establishment of a personal microbiome that is not entirely optimal, which is then linked to significantly higher incidences of allergies, atopy, and other autoimmune problems up to intestinal inflammation, obesity, diabetes, or multiple sclerosis.
Some maternity units already address this issue by placing a swab in the mother’s vagina during a cesarean section and then placing it in the newborn’s mouth and applying it to the baby’s body.
At this point, we arrive quite logically at gnotobiology, which is the field that studies germ-free animals. It is a model that allows observing the function of individual elements of the bacteriome by disabling them, or alternatively, by the partial additional introduction of some of its elements. For example, it turns out that germ-free (germ-free) mice are much more motorically active and show less anxiety than their standard-microbiome-equipped peers. Here the research on the influence of the microbiome on human behavior begins, which in animals already gives some answers, though those cannot yet be mechanically applied to humans.
Certain analogies do exist, though. When we introduce the microbiome from obese animals into the gut of germ-free mice, they begin to gain weight on the same diet composition. In humans, it is also now demonstrated that one cannot simply count calories/joules mechanically; one also needs to account for how food will be processed and used, and that depends on the microbiome. In other words: you are not what you eat, you are what your bacteria eat.
Author: MUDr. Radkin Honzák, CSc. References
(1) Collen A: 10 % člověka. Dobrovský (knihy Omega), Prague, 2015 (2) Perlmutter D: Brain maker. Yellow Kite, London, 2015 (3) Louveau A, Smirnov I, Keyes TJ, et al.: Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337-341 (4) Moeller AH, et al.: Rapid changes in the gut microbiome during human evolution. Proc Natl Acad Sci U S A. 2014;111(46):16431-5 (5) Lyte M: Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes, 2014;(5):381-389,2014