The review considers the regulatory capabilities of the human microbiota to preserve human health. The problem is not new, but it has expanded with the inclusion of new “findings” since the time of I.I. Mechnikov, a staunch supporter of the useful (protective) function of the normal flora. The study of the integration of human metabolism and microbes inhabiting human body revealed the participation of microbial metabolites — “signaling molecules” — in providing the homeostasis of the host. Particular attention  is paid to the metabolic products aromatic amino acids as regulators of the physiological functions of humans and microbes. “Signal” molecules regulate the microbial “quorum”, the immune system (its cellular and humoral components). Opiates, hormonal peptides, in particular, natriuretic hormone, hypothalamic nonapeptides (oxytocin and vasopressin), which have both a direct antimicrobial and an indirect effect in the host's body, are not ignored. Researchers are also showing interest in the products of adipose tissue — “adipokines” (in particular, leptin), which turned out to be a multipurpose regulator showing a pro-inflammatory nature. The category of “signaling” molecules also includes cytokines that interact with gram-positive bacteria, which is actively discussed in the literature. In the evaluation of the material presented on various models of infections, a general pattern is observed: under the conditions of symbiosis, a “single regulatory environment” is formed, in which a variety of connections from immediate (direct) interactions are noted, i.e. the destruction of “signaling” molecules, induction of physiological functions due to the presence of similar receptors with ligands and, finally, modification of “signaling” molecules, i.e. expansion of the spectrum of action. The combination of this variety of integration mechanisms in this “single regulatory environment” (microorganism-host) probably leads to the formation of homeostasis, i.e. dynamic balance of the “signaling” systems of the microbiota and humans in the conditions of associative symbiosis, where an infection is its model system. This concept fits well our method of intermicrobial recognition of friend-foe in the dominant-associate pair and the described triangle: microbiota-hypothalamic-pituitary neurosecretion-oxytocin, organically constituting the gut-brain axis.

/pdf/the-role-of-microbiota-in-the-regulation-of-homeostasis-in-3oyi5zjz1u.pdf

The role of microbiota in the regulation of homeostasis in the human body during infection

Research objective consisted in the development of a unified approach to the evaluation of severity of experimental tularemia disease based on the morphometric analysis. Experimental tularemia infection was morbidized in Guinea pigs, both female and male, using subcutaneous inoculation with virulent tularemia microbe cultures. Subsequent to the results of morphometric analysis, selected was a range of indicators characterizing intensiveness of dystrophy, necrobiotic and necrotic processes, infiltrate changes within cells and tissues of the infected animals to fullest extent, and reflecting a life-support system functioning state adequately. Thus, application of quantitative counting to distinguish the changes in experimental animals, while modeling specific infectious process, allowed for standardization and verification of severity evaluation approach and facilitated increase in quality of experimental investigations.

/pdf/estimation-of-the-severity-of-experimental-tularemia-against-jfwznzzvgk.pdf

Estimation of the Severity of Experimental Tularemia against a Number of Morphometric Characteristics

The topic of human–microbe interactions is of unfading relevance. Which interactions take place? Are microbes of any use, or are they essentially harmful? As the years go by, new microbiological techniques emerge, new facts on the coexistence of microbes and humans are revealed, and a new understanding of the coexistence of humans and microbes emerges. Mechanisms that underlie the natural protection of the host organism from infections are addressed in this article. The three interconnected components of the defense system considered here are the hypothalamic-pituitary system, oxytocin, and the microbiota. At first glance, these structures appear independent: the human brain contains the central “control panel” that regulates behavior, decision-making, and health. It regulates the functions of the major vitally important organs through the production of the neurohormone oxytocin, and recent studies revealed the contribution of the gut microflora (microbiota) to this regulation. Thus, the circle is closed. One can then ask whether microbes really control us. Let us address this question.

Natural Mechanisms that Underlie the Defense of Host Organisms against Infections

The growth rate of the vegetative forms and the recultivation rate of the uncultivable forms of Salmonella isogenous strains, one of these strains carrying mutation in gene pqi, were studied. The multiplication rate of the vegetative and uncultivable forms of Salmonella control strain in the spleen of infected animals at the initial stages of the infectious process was shown (in vivo) to be considerably accelerated after the preliminary incubation of the culture with cytokine (tumor necrosis factor). The multiplication rate, in vivo and in vitro, of Salmonella vegetative and uncultivable forms with mutation in gene pqi did not change after the incubation of the cells with cytokine, which is indicative of an important role played by the product of this gene in the process of the interaction of bacteria with cytokines. The full nucleotide sequence Salmonella gene pqi was determined.

Influence of tumor necrosis factor on the growth of vegetative and nonculturable forms of Salmonella

The authors present a review containing their own and literature data on the role of cytokine TNF-alfa in infectious process on the part of the macro- and microorganism, paying special attention to the latter. The paper contains data from literature concerning the mechanism of the interaction between cytokine and eukaryotic cells and experimental data on direct interaction between cytokine and bacterial cells in vitro and in vivo.

[The role of tumor necrosis factor-alfa in the interaction between the macro- and microorganism].

The goal of this work was to elucidate the mechanism of the direct interaction of bacteria cells with tumor necrosis factor (TNF-α, cytokine). It was shown previously that this interaction facilitated the activation of the bacterial growth and recultivation of noncultivated forms in vitro and in vivo. Mice deficient in genes that encode eukaryotic TNF-α receptors were infected with salmonella cells. When exogenous TNF-α was introduced into the suspension of the infected cells, the infection process (seeding of bacteria from spleens) started one day earlier in both the knockout and control mice, in comparison with that in the absence of cytokine. Bacteria are therefore able to interact with cytokine, even in the absence of eukaryotic receptors. The specificity of the bacteria-cytokine interaction was demonstrated and bacterial protein EF-Tu, which mediates the direct interaction of bacteria with cytokine, was identified using the method of immobilization of the recombinant protein TNF-α-spacer-CBD on cellulose.

Mechanism of interaction of tumor necrosis factor (TNF-a) of macroorganism with Salmonella Enterica cells (Ser. Typhimurium)

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Influence of tumor necrosis factor on the growth of vegetative and nonculturable forms of Salmonella

[The role of tumor necrosis factor-alfa in the interaction between the macro- and microorganism].

Mechanism of interaction of tumor necrosis factor (TNF-a) of macroorganism with Salmonella Enterica cells (Ser. Typhimurium)