SUBSTANTIATION
As recently as 200 years ago, the average human life expectancy was between 31 and 39 years. We now know that most people at that time died of either infections or violence.
But the concept of "infection" did not even exist then. Diseases were named by their outward signs: plague was the black death, cholera the blue death, or by their symptoms: jaundice, consumption, tetanus, whooping cough, poliomyelitis - polio. Rarely the name included a supposed cause, such as venereal disease (from the goddess of love Venus) or malaria - "bad (mala) air (aria)", but even these quasi-pathogenetic explanations, as it turned out later, were taken literally from the air.
From today's point of view, this situation is quite strange, because microorganisms have been known since the time of Galileo. As early as 1676, Antoni van Leeuwenhoek described in detail their microscopic diversity and presence in the human body, but medicine at that time did not associate microorganisms with disease, as they seemed to be everywhere.
The situation changed dramatically when isolated species were successfully cultivated and studied one by one. It was progressively realized that some bacteria can be correlated with specific diseases or conditions. With the establishment of causality, diseases caused and carried by bacteria were called infections. An era of exciting discovery of more and more pathogens and the search for ways to control them began. As a result of targeted infection control, human life expectancy doubled in just 50 years and the incidence of incurable bacterian infectious diseases fell to zero.
Today it is believed that people hardly ever die from infectious diseases in developed countries. But is it true, or is medicine as wrong, as it was 200 years ago? After all, doctors in those days were quite enlightened, and even today we are surrounded by many microbial diseases, that medicine, like two hundred years ago, describes and treats only by symptoms and does not consider as infections. Tonsillitis, appendicitis, colitis, diverticulitis, stomatitis, periodontitis, phlegmon, bacterial vaginosis - what do we know about these diseases? Only that there is no way around bacteria. Treatment is the same as before the XVIII century, purely empirical, "by eye" and even surgical. Surprisingly, even in the XXI century we try to defend ourselves with a knife against invisible enemies - is it not a paradox?

What about such seemingly purely “non-infectious” diseases such as cancer, cardiovascular, autoimmune and metabolic disorders?
In all these diseases, infections play a crucial role those impact we are only beginning to realize. Helicobacter pylori and gastric cancer, HPV and cervical, penile, rectal, vulvar, vaginal and oral cancers, EBV and lymphoma, Schistosoma/E. coli and colon cancer. The number of infectious precursors to cancer is constantly increasing. Are cancerous tumors possible without infections? Let us also mention acute rheumatism and tonsillitis, Leffler's syndrome, Wegener's granulomatosis, reactive arthritis, pancreatitis and diabetes, myocarditis and heart failure, acute coronary syndrome and the unknown “storms” of anti-inflammatory cytokines. All these examples show that poorly characterized infections and are still a major determinant of human longevity.
How is it possible that despite the obvious involvement of microorganisms in the development of these diseases, we very rarely recognize their infectious etiopathogenesis - on the contrary, we believe that "this is something else"?
The reason for this denial is the polymicrobial nature of most of these infections. Methods to confirm the presence of microorganisms, whether by culture, PCR or sequencing, are of little help in understanding the disease when multiple pathogens are involved. Listing the participants alone does not clarify their roles and the nature of their interactions with each other or with the host. Let us open a contemporary textbook of medicine: all the infections mentioned there are mono-infections. But is this not strange? In the natural environment, bacterial species rarely exist separately, and when they do occur in mixtures, they never behave as a disorderly pile of individuals. Sometimes they compete, more often they cooperate with each other, but in any case they form complementary communities that solve their tasks together. The behavior of the communities differs from the sum of the characteristics of their individual participants – as much as the capabilities of a multicellular organism differ from the qualities of its constituent cells. Even the most thorough study of individual brain cells cannot cover the workings of this organism. Similarly, the study of polymicrobial consortia based solely on the characteristics of their individual members does not promise success.
What do we know about the pathogenic role of polymicrobial communities? Not very much.
Infections caused by pathogenic duos, triplets, quartets or more complex communities are virtually unknown to modern medicine and were not even considered a real possibility until recently.
There is no doubt that modern molecular genetic diagnostic methods have greatly enhanced our understanding of the human microbiome. Sequencing-based assays are revealing an increasing diversity of microorganisms in the body and on its mucosal surfaces. All of these data are presented as lists of unrelated contributors.
The listing of microorganisms in the examined material, carried out with the help of modern microbiological methods, gives the impression of a more or less random mixture. This judgment is far from reality. No combination of bacteria is random. Their entry, location, survival and pathogenic potential depend on specific group settings.
Even the most complete enumeration of celestial bodies cannot answer the question of whether the Sun revolves around the Moon, nor where - in the Solar System or in the Andromeda Galaxy? To understand the role of celestial bodies, it is necessary to trace their exact location in relation to each other in space and time.
The same problems arise when analyzing lists of identified microorganisms. Bacteria are tiny compared to the material in which they are analyzed. For microorganisms, a smear, a punctate, or a surgically removed tissue represent entire "universes”. Detecting bacteria here does not tell us where exactly they are located nor how they are grouped in relation to each other and to the organism. Whole cell ribosomal in situ hybridization or Cell FISH fills this knowledge gap.
There are 103-105 ribosomes in each bacterium. The structural RNA is invariant and species specific. Typically, ribosomal structural RNA molecules are distinguished by their sedimentation rates (5S, 16S, 23S RNA, etc.). By hybridizing ribosomes with fluorescent dye-labeled oligonucleotides, bacteria can be stained according to their taxonomic affiliation at the species, family, order, or domain level.
As bacteria are literally packed with ribosomes, ribosomal Cell-FISH does not stain individual genes, but rather bacteria as a whole, allowing the identification under the microscope
of where they are, what consortia they form, and what they avoid - are they disperse, cohesive, or adhesively organized? Cell-FISH can also reveal the relationship of bacterial consortia to the host: detached, attached or invasive, and the changes in their structure as they move from one state to another. The diverse world of interspecies relationships, far beyond the simple presence or absence of pathogens, was revealed by using Cell-FISH to study the microbiome of the gut, mouth, and vagina.
The vaginal microbiome and bacterial vaginosis have proven to be prime examples of the importance of interspecies cooperation in the initiation, progression, and spread of polymicrobial infections.
Ribosomal Cell-FISH revealed that in contrast to the vaginal microbiota of healthy women, where bacteria are dispersed, rare, and structurally unrelated, microorganisms in the vagina of affected women form stable polymicrobial consortia organized into cohesive sludge or cohesive-adhesive biofilms. The framework of such consortia is a complex ecosystem in which several bacterial groups are integrated. Like a meadow or a forest (which, in addition to the grasses and trees that make it up, is also home to various insects, birds and animals), a polymicrobial biofilm with a Gardnerella backbone provides a habitat for a large number of microorganisms, leading to an increase in the microbial diversity that is so characteristic of bacterial vaginosis. In this way, the biofilm allows many bacteria to gain direct access to the vaginal epithelium, bypassing its defense mechanisms and explaining epidemiologic data showing a twofold or more increased risk of sexually transmitted infections in patients with bacterial vaginosis.
What does this give bacteria and what does it lead to?
Bacteria are much older than eukaryotes. As early as 4 billion years ago, they formed polymicrobial communities in tromatolites. Deposition of minerals at the base of the biofilm caused it to grow concentrically around the fossilized sediments below, hence the name stromatolite. By working together, a group of microorganisms could not only survive, but thrive in conditions that were impossible at an individual level. Of course, once a group of microorganisms formed and felt the benefits of community, such a group could not break apart. Where habitat conditions were so unfavorable that individual species making up the biofilm could not survive alone and cooperation was essential for survival, separation became impossible.
The same principle applies to the epidemiology of bacterial vaginosis, where pathogenic consortia can only grow and spread if they are transmitted as a whole. It becomes clear why biofilm  vaginosis infection is possible only with vaginal discharge and occurs sexually or by insemination. Under conditions of active immune resistance of a healthy organism and antagonism of its local microbiota to uninvited guests, as observed in the case of Lactobacillus crispatus, new colonizers do not have enough time to wait for the approach of all other participants necessary for the formation of a complex biofilm.
The available data suggest that single pathogens such as Gardnerella spp. or Lactobacillus iners are necessary but not sufficient for the formation of cohesive sludges or biofilms. Successful colonisation of the vagina requires the combined action of various structurally organised and functionally additive accomplices. Who are they, how many are there, how are they organised, what exactly do they contribute to the infectious potential of consortia?
It is still unclear which additional genes and species are absolutely necessary for the structural development and colonization of polymicrobial consortia, or which components increase their virulence and contribute to antibiotic resistance and immunity. It is, however, obvious that polymicrobial consortia in bacterial vaginosis are not a transient phenomenon that quickly emerges and disappears depending on random factors, but a process of long-term co-evolution of cooperating species.
Currently, it is not known how long or how often de novo biofilm formation occurs, or even if it is possible in a single lifetime.
It is likely that successful polymicrobial biofilms take years, if not millennia, to become established. Bacteria are much older than humans. A billion and a half years ago, stromatolite biofilms populated every corner of the planet and reached sizes of up to 10 meters. With the emergence of eukaryotes, these monsters disappeared. Eukaryotes simply ate them. But did the biofilms and other polymicrobial communities that supported them disappear along with the stromatolite skyscrapers? Definitely not. They became invisible to the naked eye, scattered across numerous niches of our planet, growing and evolving, honing their skills in the changing, increasingly unfriendly world around them. Of course, their composition in different niches corresponds to the conditions there.
The group interactions that have evolved and proven themselves over 4 billion years are embedded in their genes and allow polymicrobial consortia to continue to successfully resist much more advanced eukaryotes. The result is impressive. Yet the mass of all animals on Earth is only 35% of the combined mass of bacteria.
Modern clinical microbiology does not see and often does not even consider microbial cooperation as a significant factor in pathogenesis. This situation is unacceptable.
It is time to move away from the isolated view of infection as a result of the action of single insurgents and turn our attention to the identification and clarification of the mechanisms and consequences, prevention and treatment of polymicrobial infections.
The founding of the International Society for Polymicrobial Infections and Novel Diagnostics (In-SPIN) is intended to promote research in this field
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