MICROBIOLOGY - M.H. Serhiichuk - 2008

Chapter 11. ANTIBIOTICS. PROBIOTICS

Probiotics

Human vital activity is impossible without the normal functioning of a unified ecological complex consisting of a macro- and microorganism. Over the past 20–30 years, there has been an increase in the number of various pathological states rooted in the disruption of the normal microbiocenosis of the Human and Animal Organism — dysbiosis.

Dysbiosis, either as an independent disease or when it complicates the course of other pathological processes, requires specific therapeutic agents for Treatment. The action of these agents is based on enhancing the host's resistance, creating favorable conditions for restoring the quantitative and qualitative COMPOSITION OF THE normal microflora, and eliminating or drastically reducing the number of opportunistic microorganisms. Microorganisms representing the obligate or transient microflora of the intestine are used as the main component of such preparations.

One of the Features of the relationship between the normal microflora and the macroorganism is the presence of immunological tolerance to its representatives in The Human Body, which is formed prenatally. Even before birth, pre-T-suppressors with receptors for Representatives of the normal microflora accumulate in the child's body.

Bacteriotherapy, based on THE PRINCIPLE OF using live microorganisms, began to develop intensively from the late 1950s, when Methods and Means for the isolation, identification, and cultivation of anaerobic microorganisms—which constitute approximately 90% of the entire intestinal microflora—were refined. A little more than half a century ago, S. Waksman sadly noted: "Among microbiologists, there are not so many scientists who, taking an interest in what useful microbes do, would control and direct their activity for the benefit of man." In recent years, A large number of commercial preparations for the correction of the gastrointestinal tract microbiocenosis have been produced, such as Acinex, Biosporin, Bifidumbacterin, Colibacterin, Lactobacillin, Liobifidus, Mutaflor, Linex, and many others.

In cases of significant deviations in the composition of the intestinal normoflora, the administration of microbial cultures in specific doses is necessary. Live lyophilized cultures of microorganisms representing the normoflora of the human gastrointestinal tract are called Probiotics or eubiotics.

The compositional makeup of probiotics is quite diverse: these include probiotics based on only a single strain of a microorganism, as well as preparations containing a specific number of Bacteria with mutually complementary Functions.

Microbial cultures used for the formulation of probiotics must meet the following requirements:

- possess a broad spectrum of antagonistic activity against pathogenic microorganisms while not inhibiting The Development of the normal microflora;

- be completely safe for the environment.

In addition, it is advisable to use strains that are resistant to commonly used Antibiotics and enhance the host's defense

reactions (e.g., the phagocytic activity of Blood Leukocytes, the induction of endogenous interferon, etc.).

A prerequisite when creating probiotics is also the ability of the cultures included in their composition to maintain their biological activity for at least 12 months.

The most widespread are probiotics containing bifidobacteria, lactobacilli, and Escherichia coli, or combinations thereof.

Bifidoflora is one of the natural defense factors of the organism. The normal microflora, which consists of 85–98% bifidobacteria, stimulates protective and adaptive mechanisms in newborns and serves as a reliable barrier preventing the development of opportunistic microorganisms. Disruptions in the microflora create a pre-disease state that can develop into an illness under various aggravating circumstances (immunodeficiencies, enzymopathies, hereditary Metabolic Disorders, radiation injuries, stress states, etc.). DISEASES ASSOCIATED WITH intestinal dysbiosis can acquire a chronic, relapsing course. All of this necessitates maintaining an optimal level of bifidobacteria in the intestine both in children from the first day of life and in adults. The industrial production of the domestic preparation based on bifidobacteria (bifidumbacterin) began in 1971. It is used primarily for Disorders of the intestinal anaerobic flora and can be prescribed from the first days of a newborn's life. Thus, The Use of the preparation in infants from the first day of life—especially those on artificial feeding and belonging to the "risk group"—leads to the normalization of bifidoflora formation dynamics, a reduction in diathesis manifestations, and a significant improvement in health status.

The MECHANISM OF ACTION of bifidumbacterin is complex and not yet fully understood. When creating biological preparations from analogs of the obligate microflora of the gastrointestinal tract (bifido- and lactoflora), primary attention is paid to the ability of these bacteria to adhere to The surface of the intestinal epithelium. It is known that one of the consequences of dysbiosis is the denudation of the intestinal epithelium and the potential for enteropathogenic bacteria to penetrate through unprotected areas into the blood and Organs. When administering probiotics based on bacteria with high adhesive activity, competition for attachment sites is artificially created.

Another important link in ensuring the maximum positive effect is antagonistic activity, which in bifidobacteria is driven by strong acid production, the synthesis of Lysozyme, and The production of B-group Vitamins.

Most commonly, bifidoflora-based probiotics include: Bifidobacterium adolescentis, B. animalis, B. bifidum, B. infantis, B. longum, and B. thermophilum.

Another well-known group of microorganisms upon which a large number of probiotics are based is lactobacilli. Probiotics containing lactobacilli include: Lactobacillus plantarum, L. casei, L. amylovorus, L. lactis, L. acidophilus, L. delbrueckii subsp. bulgaricus, L. brevis, and others.

The Mechanism of action of lactobacilli-based probiotics is analogous to that of bifidobacteria-based probiotics. In lactobacilli, the inhibitory effect is also associated with strong acid production. Their antagonistic action is driven by the production of such antibiotic substances as lysozyme, lactic acid, and hydrogen peroxide. The released hydrogen peroxide becomes part of the bactericidal SCH-lactoperoxidase system, which functions on the mucous membranes of Body Cavities connected to the external environment. This system contains lactoperoxidase, SCH ions, and endogenous hydrogen peroxide produced by the indigenous lactic acid flora, which enhances the action of IgA. The efficacy of the lactoperoxidase system is heightened upon the administration of lactobacilli. Indigenous lactobacilli stimulate general Immunity and the nonspecific resistance of the macroorganism. Lactobacilli increase the functional activity of polymorphonuclear leukocytes, stimulate monocyte migration, and enhance peritoneal macrophage activity. Lactobacilli-based probiotics boost cellular and humoral responses, making it possible to use them as oral adjuvants. Probiotics containing L. acidophilus can suppress the action of Enzymes that catalyze The conversion of procarcinogens into carcinogens. A reduction in human blood Cholesterol levels is also associated with the METABOLIC ACTIVITY OF lacto- and bifidobacteria-based probiotics.

In the 1950s, L. Perethetz conducted work on creating colibacterin from a live culture of Escherichia coli possessing antagonistic activity. The mechanism of the protective action of colibacterin is multifaceted: competition for nutrient sources, intensive reproduction, acid production, accumulation and excretion of toxic metabolites, enzymatic activity, The ability to stimulate immunity, and the colonization of the intestinal mucosa.

Escherichia coli has served as the basis for the creation of other preparations: normoflorin, coliflorin, sevacol, mutaflor, normoflora, and others.

Seeking to increase the therapeutic efficacy of probiotics, researchers incorporate substances that activate Cell Division of the core probiotic cultures into their composition. Such preparations are called synbiotics or conbiotics.

Substances that stimulate the growth of normal microflora (prebiotics) include:

- Monosaccharides and sugar alcohols (xylose, xylobiose, raffinose, sorbitol, etc.);

- Oligosaccharides (lactulose, fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, etc.);

- Polysaccharides (Pectins, dextrin, inulin, etc.);

- enzymes (β-galactosidase of microbial origin, saccharomycete proteases, etc.);

- Peptides (soy, milk, etc.);

- antioxidants (vitamins C, E, etc.);

> Unsaturated Fatty acids (eicosapentaenoic acid, etc.);

> organic acids (propionic, acetic, etc.);

> plant extracts (carrot, potato, corn, rice, pumpkin, garlic, etc.).

The primary criterion for the effectiveness of most biological products based on endogenous microflora (lactobacterin, bifidumbacterin, etc.) is a high competitiveness in colonizing the intestinal epithelium. The phenomenon of microbial antagonism has also found widespread application in the development of probiotics. Particularly pronounced antagonistic properties are characteristic of aerobic spore-forming bacteria of the genus Bacillus.

The first reports on the use of live microorganisms of the genus Bacillus in human and veterinary medicine appeared in France in the 1950s, when it was established that during the germination of B. subtilis spores, A number of enzymes are produced that are capable of lysing Cells of staphylococci, proteus, and certain other opportunistic and pathogenic bacteria.

In the 1970s, the Yugoslav association "Galenika" launched the commercial preparation Bactisubtil, which was recommended for individuals suffering from dysbiosis resulting from Antibiotic therapy for INFECTIOUS DISEASES OF various etiologies.

Various biological products derived from bacilli are based on B. subtilis, B. cereus, B. polymyxa, B. coagulans, B. brevis, B. megaterium, B. pumilus, B. laterosporus, and B. licheniformis.

For all probiotics consisting of bacteria of the genus Bacillus, the onset of their action is considered to be the time of their oral administration. Following brief and partial contact with the mucosa of the oropharynx and Esophagus, the probiotics—which are a lyophilized bacterial biomass—begin their active function right in The Stomach. Immediately upon entering the body, regardless of the physicochemical parameters of the gastric contents, spore germination begins, accompanied by the intensive production of certain physiologically active substances.

It is believed that the positive effects of bacillary probiotics are primarily associated with the production of antibiotic substances. About 200 antibiotics produced by various species of bacilli are currently known. B. subtilis is the most productive species among the bacilli. Bacilli are capable of producing antibiotics under both aerobic and anaerobic conditions. Bacillary antibiotics are diverse in their Structure and mechanism of action.

The antimicrobial activity of bacillary metabolic products may also be attributed to the synthesis of lytic enzymes capable of lysing both gram-negative and gram-positive bacteria.

While the aforementioned manifestations of the biological activity of probiotics in the gastrointestinal tract are local in nature, they can simultaneously exert a more systemic effect. For instance, in the blood of animals that received an oral bacillary biological product, an increase in cellular phagocytic activity was observed alongside translocation processes.

Another key mechanism of the positive impact exerted by probiotic microorganisms on the host organism is The stimulation of its Immune Response, which is associated with the phenomenon of organ-tissue translocation of these bacteria.

Given the high therapeutic efficacy of probiotics and the absence of adverse effects during their use, they are increasingly becoming an alternative to chemotherapeutic drugs or a unique Supplement to pharmacotherapy.