Additional information for Specialists
PROBIOTICS, PREBIOTICS AND SYNBIOTICS – PREPARATIONS
REGULATING THE NORMAL INTESTINAL MICROFLORA
REGULATING THE NORMAL INTESTINAL MICROFLORA
The problem of intestinal microbiology in recent years is attracting more and more attention not only from gastroenterologists, but also from other specialists (pediatricians, neonatologists, infectious disease specialists, bacteriologists). It is known that the microecological system of the organism, both in the individual and in children is a very complex, from a phylogenetic point of view, dynamic complex, including diverse in quantitative and qualitative composition associations of microorganisms and products of their biochemical activity (metabolites) in certain living conditions and habitat .
The state of dynamic equilibrium between the organism of the “owner”, the microorganisms inhabiting it and the environment is accepted to be called “eubiosis”, in which human health is at an optimal level .
The composition of the intestinal flora in children after 2 years of age is practically indistinguishable from the composition in the adult: more than 400 species of bacteria, most of which are anaerobic, difficult to cultivate. All bacteria enter the gastrointestinal tract (GIT) orally. The density of bacteria in the stomach, jejunum, ileum and colon, respectively, is equal to 1,000, 10,000, 100,000 and 1,000,000 in 1 ml of the contents of the intestine [3-4 ].
The table shows the typical representatives of the normal intestinal microflora in an adult, divided into two main groups according to the nature of metabolism:
(different species) **
(different species) **
There are many reasons why there is a change in the ratio of normal microflora in the digestive tract. These changes can be both short-term – dysbacterial reactions and long-term – dysbacteriosis .
Dysbiosis is a condition of the ecosystem in which the functioning of all its components is disrupted – the human body, its microflora and its environment, as well as the mechanisms of their interaction, which leads to various diseases. Intestinal dysbacteriosis (MS) is understood as qualitative and quantitative changes characteristic of the given biotype of human normoflora, leading to pronounced clinical reactions of the microorganism or appearing as a consequence of any pathological processes in the body . MS should therefore be considered as a complex of symptoms and not as a disease. It is quite obvious that MS is secondary, ie. consequence of an underlying disease.
Drugs that are taken to improve the function of the digestive tract, to regulate the microbiocenosis of the gastrointestinal tract, for the prevention and treatment of certain specific infectious diseases are divided into probiotics, prebiotics, synbiotics, bacteriophages and biotherapeutic agents [2,7]. The first three groups are united in one – probiotics. Taking probiotics and prebiotics leads to the same result – an increase in the amount of lactic acid bacteria, natural inhabitants of the intestine. Table 2 shows some widely used pro- and prebiotics:
Table 2 shows some widely used pro- and prebiotics:
* Indicator of the degree of polymerization
Probiotics are living microorganisms: lactic acid bacteria, most often bifidobacteria or lactobacilli, sometimes the intestinal bacterium E-coli M-17, some types of gram-positive cocci, yeast, which as follows from the term “probiotic” refer to the normal inhabitants of the intestinal tract in a healthy person .
Preparations – probiotics based on these microorganisms are widely used as food additives, as well as in yogurt and other dairy products. The microorganisms that are part of probiotics are non-pathogenic, non-toxic, contained in sufficient quantities, retain their viability during storage and passage through the gastrointestinal tract [8,9]. Probiotics are not considered medicinal products, but are considered as agents that have a beneficial effect on human health and have no toxic or pathogenic effects on the body.
The safety of probiotics is confirmed by the fact that the WHO, FDA and FAO UN (Food and Agriculture Organization of the United Nations) conclude that probiotics are generally safe products and have GRAS (Generally Regarded As Save) status, ie. they can be used without restriction in the pharmaceutical and food industries.
Brief characteristics of the genera of microorganisms  and data on their quantitative status in the microbiocenosis in the lower part of the gastrointestinal tract in a healthy person 
BIFIDOBACTERIA – these are anaerobic bacteria, morphologically represented by extremely variable in shape gram-positive non-spore-forming rods, slightly curved or pin-like and often branched. The ends of the bifidobacterial cell can be bifurcated, thinned or thickened in the form of an inflated balloon. The arrangement of the cells is single, in pairs, V-shaped, and sometimes in a chain or in the form of a rosette.
Most of the bifidobacteria inhabit the large intestine and are its main microflora. In children, bifidobacteria make up the majority of all germs in the gut, depending on age.
Thus, bifidobacteria occupy a dominant position in the microbial landscape in healthy newborns who are breastfeeding, about 5-20 days after birth. The normal amount of bifidobacteria in infants is 1010-1011 CFU / g of feces, and in adolescence and in adults – 109-1010 CFU / g.
LACTOBACYLS – are non-spore-forming gram-positive rod-shaped bacteria, usually of regular shape, long, sometimes coccoid, arranged in short chains or singly.
Lactobacilli inhabit the body of the newborn baby in the early postnatal period. The habitat of the lactobacilli are the various departments of the gastrointestinal tract, starting from the oral cavity and ending with the large intestine, where they maintain a pH of 5.5-5.6.
Constantly present in the body, and in many periods of life of girls and women of reproductive age represent the predominant flora of the fulva and vagina. Lactobacilli are also found in human and animal milk.
In the stomach lactobacilli are contained in an amount of 102-103 CFU / ml gastric juice, in the small intestine – up to 103-104 CFU / ml intestinal juice, in the colon (depending on age) – 106-107 CFU / g feces, in the vagina – 106-109 CFU / ml vaginal contents (depending on age).
In the course of their vital activity, lactobacilli enter into a complex interaction with other microorganisms, as a result of which putrefactive and gonorrheal opportunistic pathogens are suppressed, first of all proteins, as well as the causative agents of acute intestinal infections. In the process of normal metabolism they are able to form lactic acid, hydrogen peroxide, to produce lysozyme and substances with antibiotic activity: reuterin, plantaricin, lactocidin, lactolin.
Lactobacilli are the second major microbiological link in the formation of colonization resistance in the open cavities of the body.
ENTEROCOCCI– occur in the intestine in quantities of 105-107 CFU / g of faeces and normally do not exceed the total amount of intestinal bacteria. Enterococci metabolize the so-called “Wandering” type, ferment a variety of hydrocarbons with the formation of mainly lactic acid, but not gas, lowering the pH to 4.2-4.6.
In some cases, especially lactopositive ones, they restore nitrate. In experiments with gnotobionts, it was found that when sterile animals were removed through the barrier without oral administration of enterococci, a lethal viral infection was observed.
ESCHERIHIA COLI are the first settlers in the intestines of newborns. They prepare the environment for anaerobic microorganisms by absorbing oxygen, which diffuses from the systemic bloodstream through the intestinal wall and enters the intestine.
Experiments on the colonization of microbes in the intestines of gnotobiological animals have shown that anaerobic bacteria settle in the gastrointestinal tract only after its colonization with anaerobic bacteria, primarily Escherichia coli.
Escherichia coli is known to help hydrolyze lactose, participate in the breakdown of proteins and carbohydrates, in the metabolic conversion of cholesterol, in fatty and bile acids, synthesize B vitamins, vitamin K, nicotinic and pantothenic acid. Regulators of the level of bacteria in the intestine are various exoenzymes and bacteriocins. Synthesized bacteriocins are characterized by molecular weight and spectrum of antimicrobial activity.
So: the quantities having a high molecular weight are characterized by a narrow spectrum of antibacterial action, because in a specific way, they suppress the level of bacteria of the same species or of phylogenetically related species, at a time when low-molecular-weight microcins have a broad spectrum of antagonistic activity.
The colonization of the intestinal mucosa with Escherichia coli is also determined by their ability to compete with opportunistic bacteria for food sources.
Also important is the ability of Escherichia coli (lipopolysaccharide) LPZ and, apparently, bacteroids to cause significant, nonspecific stimulation of humoral and cellular immunity, inducing the synthesis of neutrophil cells, regulating the cooperative interaction of phagocytes and anti-inflammatory cytokines (TNF-α, IL-1q IL-6, etc.), which are important for the cooperative interaction of immunocompetent cells.
Escherichia coli LPS play an important role in maintaining antiendotoxin immunity, protecting the organism from endotoxin shock. In the human intestine Escherichia coli appear in the first days after birth in an amount of 107-108 CFU / g of feces and are stored throughout life at the level of 106-108 CFU / g contained in the colon.
Therefore: probiotic preparations are effective regulators of the normal microflora of the gastrointestinal tract. The microbes contained in them are well studied and recognized by the WHO as harmless to humans. In addition, the best proof of the safety and effectiveness of probiotics is half a century of their practical use (Medicines, dietary supplements, probiotic-enriched dairy products) and their intake by millions of people around the world.
Prebiotics are preparations of non-microbial origin, capable of having a positive effect on the body of the “host” by selectively stimulating the growth of development, or enhancing the metabolic activity of the normal intestinal microflora [2,3,11,12]. This group includes preparations that belong to different pharmacotherapeutic groups, but have common properties – they stimulate the growth and development of the normal intestinal microflora.
Most prebiotics are substrates for various types of microbial components of the normal microflora of the gastrointestinal tract. The effect of prebiotics is as follows: they lower the pH of the stool; reduce ammonia production; activate immunity; reduce the potential development of clostrid, candida, listeria, etc .; increase the absorption of Ca from food by 40-60%; enhance the energy supply and regeneration of the epithelium of the colon [12,13].
Many of the indigestible nutrients in the upper gastrointestinal tract are also prebiotics. In order to be classified as a prebiotic, a food component must have: the ability not to break down and not be absorbed in the upper gastrointestinal tract; ability to be used as a selective substrate for beneficial microorganisms, stimulating their growth or metabolic activity; ability to normalize the composition of the intestinal microflora and to induce local and systemic responses beneficial to the body as a whole .
From the above it is clear that prebiotics, as a class of physiologically active substances, are biologically active food additives (BAA). All prebiotic-based products in circulation are classified as dietary supplements.
– Oligosaccharides: lactulose, fructooligosaccharide (POPs), galactooligosaccharide (POPs) and others with a degree of polymerization (n≤10);
– Polysaccharides: inulin, dextrin, pectin, etc .;
– Other prebiotics with non-substrate action, such as: lysozyme, calcium patotenate, RAMBA (para-amino-methyl-benzoic acid), etc.
Brief description of the mechanism of action of some of the listed prebiotics.
The most important function of the intestinal bifidoflora is the fermentation of dietary fiber – oligosaccharides. The function of dietary fiber is extensive. These include: stimulation of the development of bifidobacteria and acidophilic lactobacilli; adsorption of toxic products and their excretion in the feces; satisfaction of energy needs up to 6-9%; antioxidant activity (protection of the intestinal mucosa from free radicals); creating a place for fixation for intestinal microorganisms, which determine the favorable intestinal ecology; enhancement of peristalsis .
Oligosaccharides, in unchanged form, reach the large intestine and there their breakdown occurs with the help of bacterial enzymes – glycosidases, which catalyze the breakdown of glycosidic bonds. These enzymes are usually induced, i. their formation is stimulated by adding a substrate of enzymes, which in turn serves as a factor in stimulating the development of social bifidobacteria and lactobacilli.
Lactulose– short chain fructooligosaccharides – a mixture of oligosaccharides containing glucose bound to fructose (n = 4). An oligosaccharide consisting of residual galactose and residual fructose is called lactulose (Lactulose Irop in Italy, Lactofiltrum in Russia). Lactulose enters the large intestine unchanged (only about 0.25-2.0% is absorbed unchanged from the small intestine) and serves as a nutrient substrate for saccharolytic bacteria. Lactulose has been used for more than 40 years in pediatrics to stimulate the development of lactobacilli in infants [17,18].
Fructooligosaccharides (POPs) – by means of partial enzymatic hydrolysis of inulin, POPs with an average degree of polymerization 8 – “Raphthylose” (Orafti, Belgium) are obtained .
In the reaction, the catalyzed 1,2-fructan 1-fructosyltransferase with sugar as a substrate, a low molecular weight PHF with a degree of polymerization less than 4 – “Neosugar” or “Actilife” (Beghin-Meji Industries, Paris, France) .
Inulin– a polysaccharide contained in the fruits and roots of dahlias, artichokes and celandines. It is fructosan, because its hydrolysis produces fructose. It has been shown that inulin, in addition to stimulating the development and activity of bifidobacteria and lactobacilli, increases the absorption of calcium in the colon, ie. reduces the risk of osteoporosis, affects lipid metabolism, reduces the risk of atherosclerotic changes in the cardiovascular system and, possibly, prevents the development of type II diabetes. There are preliminary data on its anticancer effect [19,20].
Calcium pantothenate– Participates in the processes of acetylation and oxidation in cells, in carbohydrate and fat metabolism, in the synthesis of acetylcholine, stimulates the formation of corticosteroids in the adrenal cortex. It is utilized by bifidobacteria and helps to increase their biomass. RAMVA (para-amino-methyl-benzoic acid) – inhibits the action of proteolytic enzymes of opportunistic bacteria and fungi, stimulates the development and reproduction of bifido- and lactoflora.
Lysozyme– helps to normalize the disturbed microflora. It is most active against gram-positive pathogenic and opportunistic bacteria. It has bifidogenic, immunomodulatory and anti-inflammatory action, stimulates metabolic and reparative processes and erythropoiesis, improves digestion, increases anti-infective antitoxic resistance, has antibacterial action and is synergistic with many antibiotics.
Therefore, probiotics are biologically active food supplements that help to normalize the condition of the gastrointestinal tract by selectively stimulating the development and / or metabolic activity of one or more groups of social bacteria inhabiting the colon.
Mixing PROBIOTICS and PREBIOTICS unites in the group SYNBIOTICS , which have a beneficial effect on the health of the host organism: facilitate the survival and survival in the intestine of live bacterial supplements; selectively stimulate the development and activation of the metabolism of endogenous lacto- and bifidobacteria .
Synbiotics – these are preparations obtained as a result of a rational combination of probiotics and prebiotics in one product. These are usually biologically active food supplements that are enriched with one or more strains of the genera Lactobacillus and / or Bifidobacterium [1,3,11,21]. In some cases, these drugs have the status of drugs.
Sinbiotici sa absorbed in itself all the useful properties on probiotic and sai efficacy class of the drug with the function for normalization on the microbiocenosis on the stomato-celiac tract.
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