Intestinal dysbiosis

Intestinal dysbacteriosis is a change in the qualitative and quantitative composition of the bacterial flora caused by a dynamic disruption of the intestinal microecology as a result of a breakdown in adaptation and a disruption of the body's protective and compensatory mechanisms.

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Epidemiology

Intestinal dysbacteriosis is very common. It is detected in 75-90% of cases of acute and chronic gastroenterological diseases.

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Causes intestinal dysbiosis

The most common and relevant causes of intestinal dysbacteriosis are the following:

1. Antibiotic chemotherapy, use of glucocorticoids, cytostatics.
2. Professional long-term contact with antibiotics.
3. Acute and chronic gastrointestinal diseases of infectious and non-infectious nature. The main role in the development of dysbacteriosis in this situation is played by opportunistic flora.
4. Changes in primary diet, abuse of sucrose.
5. Serious illnesses, surgeries, mental and physical stress.
6. A person’s prolonged stay in habitats that are not typical for him (unaccustomed to him), extreme conditions (spelunking, high-mountain, arctic expeditions, etc.).
7. Immunodeficiency states (in oncological diseases, HIV infection).
8. Exposure to ionizing radiation.
9. Anatomical and physical disorders of the intestine: anatomical abnormalities, complications during gastrointestinal tract surgeries, disorders of intestinal motility and absorption of nutrients. Malabsorption and maldigestion syndromes create favorable conditions for the proliferation of opportunistic flora.
10. Polyhypovitaminosis.
11. Starvation.
12. Gastrointestinal bleeding.
13. Food allergy.
14. Enzyme deficiencies (congenital and acquired), intolerance to various foods, including whole milk (lactase deficiency); cereals (gluten enteropathy), fungi (trehalase deficiency).

Under the influence of etiological factors, qualitative and quantitative changes in the intestinal microflora occur. As a rule, the number of the main bacterial symbionts of the intestine - bifidobacteria, lactic acid bacteria and non-pathogenic intestinal bacteria - is significantly reduced. Along with this, the number of opportunistic microbes (enterobacteria, staphylococci, etc.), fungi of the genus Candida, which are absent in the intestine or present in it in small quantities, increases. The changed qualitative and quantitative composition of the intestinal microflora leads to the fact that dysbiotic microbial associations do not perform protective and physiological functions and disrupt the functioning of the intestine.

Severe forms of dysbacteriosis cause significant disturbances in the digestive and absorption functions of the intestines and sharply disrupt the general condition of the body. Opportunistic bacteria, which inhabit the intestines in excess, disrupt the absorption of carbohydrates, fatty acids, amino acids, and vitamins. Metabolic products (indole, skatole, etc.) and toxins produced by opportunistic flora reduce the detoxification function of the liver, increasing the symptoms of intoxication.

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Pathogenesis

The biomass of microbes inhabiting the intestines of an adult is 2.5-3.0 kg and includes up to 500 species of bacteria, with the ratio of anaerobes to aerobes being 1000:1.

The intestinal microflora is divided into obligate (microorganisms that are constantly part of the normal flora and play an important role in metabolism and anti-infective defense) and facultative (microorganisms that are often found in healthy people, but are opportunistic, i.e. capable of causing diseases when the resistance of the macroorganism decreases).

The dominant representatives of obligate microflora are non-spore-forming anaerobes: bifido- and lactobacilli, bacteroids. Bifidobacteria make up 85-98% of the intestinal microflora.

Functions of normal intestinal microflora

• creates an acidic environment (pH of the colon up to 5.3-5.8), which prevents the proliferation of pathogenic, putrefactive and gas-forming intestinal microflora;
• promotes enzymatic digestion of food ingredients (bifido- and lactobacilli, eubacteria, bacteroids enhance protein hydrolysis, saponify fats, ferment carbohydrates, dissolve fiber);
• performs a vitamin-forming function (Escherichia, bifido- and eubacteria participate in the synthesis and absorption of vitamins K, group B, folic and nicotinic acid);
• participates in the synthetic, digestive and detoxifying functions of the intestine (bifido- and lactobacilli reduce the permeability of vascular tissue barriers for toxins of pathogenic and opportunistic microorganisms, prevent the penetration of bacteria into internal organs and blood);
• increases the body's immunological resistance (bifido- and lactobacilli stimulate the function of lymphocytes, the synthesis of immunoglobulins, interferon, cytokines, increase the level of complement, and the activity of lysozyme);
• enhances the physiological activity of the gastrointestinal tract, in particular, intestinal peristalsis;
• stimulates the synthesis of biologically active substances that have a positive effect on the function of the gastrointestinal tract, cardiovascular system, and hematopoiesis;
• plays an important role in the final stages of cholesterol and bile acid metabolism. In the large intestine, with the participation of bacteria, cholesterol is converted into the sterol coprostanol, which is not absorbed. With the help of intestinal microflora, hydrolysis of the cholesterol molecule also occurs. Under the influence of microflora enzymes, changes in bile acids occur: deconjugation, conversion of primary bile acids into keto derivatives of cholanic acid. Normally, about 80-90% of bile acids are reabsorbed, the rest are excreted in feces. The presence of bile acids in the large intestine slows down the absorption of water. The activity of microflora contributes to the normal formation of feces.

Obligate microflora in healthy people is constant, performs leading biological functions useful for the human body (bifido- and lactobacilli, bacteroids, E. coli, enterococci). Facultative microflora is inconstant, its species composition changes, it is quickly eliminated, does not have a significant effect on the host organism, since its contamination is low (opportunistic bacteria - citrobacter, micrococci, pseudomonads, proteus, yeast-like fungi, staphylococci, clostridia, etc.).

Quantitative composition of normal intestinal microflora

Name of microorganisms	CFU/g faeces
Bifidobacteria	108-1010
Lactobacilli	106-1011
Bacteroides	107-109
Peptococci and Peggostreptococci	105-10b
Escherichia coli	10b-108
Staphylococci (hemolytic, plasma coagulating)	No more than 103
Staphylococci (hemolytic, epidermal, coagulase-negative)	- 104-105
Streptococci	105-107
Clostridia	103-105
Eubacteria	10Z-1010
Yeast-like fungi	No more than 10Z
Opportunistic Enterobacteriaceae and Non-Fermenting Gram-Negative Rods	No more than 103-104

Note: CFU - colony forming units

The gastrointestinal tract is a natural habitat for microorganisms in humans and animals. There are especially many microorganisms in the lower section of the large intestine. The number of microbes in the large intestine of vertebrates is 10 ¹⁰ -11 ¹¹ per 1 g of intestinal contents, in the small intestine there are significantly fewer due to the bactericidal action of gastric juice, peristalsis and, probably, endogenous antimicrobial factors of the small intestine. In the upper and middle sections of the small intestine there are only small populations, mainly gram-positive facultative aerobes, a small number of anaerobes, yeast and fungi. In the distal sections of the small intestine (in the area of the ileocecal valve), the "microbial spectrum" has an intermediate position between the microflora of the proximal sections of the small and large intestines. The lower part of the ileum is populated by the same microorganisms that are found in the large intestine, although there are fewer of them. The microflora of feces, which is actually the flora of the distal colon, is more accessible to study. The advent of long intestinal probes has made it possible to study the microflora throughout the entire gastrointestinal tract.

After eating, the number of microorganisms increases moderately, but after a few hours returns to the original level.

Microscopy of feces reveals numerous bacterial cells, of which approximately 10% can reproduce on artificial nutrient media. In healthy individuals, approximately 95-99% of culturable microorganisms are anaerobes, which are represented by bacteroids (10 ⁵ -10 ¹² in 1 g of feces) and bifidobacteria (10 ⁸ -10 ¹⁰ bacterial cells in 1 g of feces). The main representatives of aerobic fecal flora are Escherichia coli (10 ⁶ -10 ⁹ ), Enterococcus (10 ³ -10 ⁹ ), and Lactobacilli (up to 10 ¹⁰ ). In addition, staphylococci, streptococci, clostridia, Klebsiella, Proteus, yeast-like fungi, protozoa, etc. are detected in smaller quantities and less frequently.

Usually, during a bacteriological examination of feces of a healthy person, attention is paid not only to the total amount of E. coli (300-400 million/g), but also to its content with weakly expressed enzymatic properties (up to 10%), as well as lactose-negative enterobacteria (up to 5%), coccal forms in the total amount of microorganisms (up to 25%), bifidobacteria (10~ ⁷ and more). Pathogenic microorganisms of the intestinal family, hemolytic E. coli, hemolytic staphylococcus, Proteus, Candida fungi and other bacteria should not be present in the feces of a healthy person.

Normal microflora, being a symbiont, performs a number of functions that are essential for the vital activity of the macroorganism: non-specific protection against bacteria that cause intestinal infections, based on microbial antagonism, participation in the production of antibodies, and the vitamin-synthesizing function of microorganisms, in particular vitamins C, K, B1, B2, B6, B12, PP, folic and pantothenic acids. In addition, microorganisms inhabiting the intestine break down cellulose; participate in the enzymatic breakdown of proteins, fats and high-molecular carbohydrates; promote the absorption of calcium, iron, vitamin D due to the creation of an acidic environment; participate in the metabolism of bile acids and the formation of stercobilin, coprosterol, deoxycholic acid in the large intestine; inactivate enterokinase and alkaline phosphatase; participate in the formation of protein breakdown products (phenol, indole, skatole), normalizing intestinal peristalsis. Normal bacterial microflora promotes the "maturation" of the macrophage-histiocyte system, affects the structure of the intestinal mucosa and its absorption capacity.

Intestinal microflora can change under the influence of various pathological processes or exogenous factors, which is manifested by a violation of the normal ratios between different types of microorganisms and their distribution in different parts of the intestine. The appearance of altered dysbiotic microflora characterizes a condition called dysbacteriosis. With pronounced dysbacteriosis, the number of microorganisms in the small intestine increases with a predominance of bacteria of the genus Escherichia, Klebsiella, lactobacilli, campylobacter and enterococcus. In the large intestine and feces, the number of bifidobacteria decreases or completely disappears, the number of Escherichia, staphylococci, streptococci, yeast, Klebsiella, Proteus increases.

Dysbacteriosis most often manifests itself by a decrease in the total number of microorganisms, sometimes to the complete disappearance of individual species of normal microflora with the simultaneous predominance of species that are normally present in minimal quantities. This predominance can be long-term or occur periodically. Antagonistic relationships between representatives of natural associations play a significant role in the development of dysbacteriosis. Small temporary fluctuations in the number of individual microorganisms are eliminated independently without any intervention. Conditions under which the rate of reproduction of some representatives of microbial associations increases or specific substances accumulate that suppress the growth of other microorganisms significantly change the composition of the microflora and the quantitative ratio of various microorganisms, i.e., dysbacteriosis occurs.

In various diseases, the small intestine is populated by microorganisms from the distal parts of the intestine, and then the nature of the microflora in it resembles the “microbial landscape” of the large intestine.

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Symptoms intestinal dysbiosis

In many patients, intestinal dysbacteriosis occurs latently and is detected by bacteriological examination of feces. Clinically expressed forms of dysbacteriosis are characterized by the following symptoms:

• diarrhea - loose stools may occur 4-6 or more times; in some cases, the consistency of feces is mushy, pieces of undigested food are detected in the feces. Diarrhea is not a mandatory symptom of intestinal dysbacteriosis. Many patients do not have diarrhea, there may only be unstable stool;
• flatulence is a fairly constant symptom of dysbacteriosis;
• abdominal pain of an inconstant, uncertain nature, usually of moderate intensity;
• malabsorption syndrome develops with prolonged and severe dysbacteriosis;
• bloating, rumbling during palpation of the terminal section of the ileum and, less commonly, the cecum.

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Stages

The degree of dysbacteriosis can be judged by the classification:

• 1st degree (latent, compensated form) is characterized by minor changes in the aerobic part of the microbiocenosis (increase or decrease in the number of Escherichia). Bifido- and lactoflora are not changed. As a rule, intestinal dysfunction is not observed.
• 2nd degree (subcompensated form) - against the background of a slight decrease in the content of bifidobacteria, quantitative and qualitative changes in Escherichia coli and an increase in the population level of the group of opportunistic bacteria, pseudomonads and Candida fungi are detected.
• Stage 3 - significantly reduced level of bifidoflora in combination with a decrease in the content of lactoflora and a sharp change in the number of Escherichia. Following a decrease in the level of bifidoflora, the composition of the intestinal microflora is disrupted, conditions are created for the manifestation of the aggressive properties of opportunistic microorganisms. As a rule, with dysbacteriosis of stage 3, intestinal dysfunction occurs.
• 4th degree - absence of bifidoflora, significant decrease in the amount of lactoflora and change in the content of E. coli (decrease or increase), increase in the number of obligate, optional and uncharacteristic for a healthy person types of opportunistic microorganisms in associations. The normal ratio of the composition of the intestinal microbiocenosis is disrupted, as a result of which its protective and vitamin-synthesizing functions decrease, enzymatic processes change, the level of undesirable metabolic products of opportunistic microorganisms increases. In addition to dysfunction of the gastrointestinal tract, this can lead to destructive changes in the intestinal wall, bacteremia and sepsis, since the general and local resistance of the body decreases, and the pathogenic effect of opportunistic microorganisms is realized.

Some authors classify intestinal dysbacteriosis according to the type of dominant pathogen:

1. staphylococcal;
2. Klebsiella;
3. Proteus;
4. bacteroid;
5. Clostridial (Cl. difficile);
6. candidomycosis;
7. mixed.

Latent and subcompensated forms of dysbacteriosis are more typical for mild and moderate forms of dysentery and salmonellosis, post-dysenteric colitis. Decompensated dysbacteriosis is observed in severe and protracted acute intestinal infections associated with gastrointestinal tract pathology, as well as in nonspecific ulcerative colitis, protozoal colitis.

The stages of dysbacteriosis can be determined using the classification:

• Stage I – reduction in the number or elimination of bifidobacteria and/or lactobacilli.
• Stage II - a significant increase and subsequent predominance of colibacterial flora or its sharp decrease, atypical and enzymatically defective E.coli.
• Stage III - high titers of opportunistic microflora association.
• Stage IV - bacteria of the Proteus or Pseudomonas aeruginosa genus predominate in high titers.

The classification of dysbacteriosis according to A.F. Bilibin (1967) deserves great attention:

Intestinal dysbacteriosis is usually a localized pathological process. However, in some cases, generalization of dysbacteriosis is possible. The generalized form is characterized by bacteremia, and sepsis and septicopyemia may develop.

Intestinal dysbacteriosis can occur in latent (subclinical), local (local) and widespread (generalized) forms (stages). In the latent form, a change in the normal composition of symbionts in the intestine does not lead to the emergence of a visible pathological process. In the local form of dysbacteriosis, an inflammatory process occurs in any organ, in particular in the intestine. Finally, in the widespread form of dysbacteriosis, which can be accompanied by bacteremia, generalization of infection, due to a significant decrease in the overall resistance of the body, a number of organs are affected, including parenchymatous organs, intoxication increases, and sepsis often occurs. According to the degree of compensation, compensated, often occurring latently, subcompensated (usually local) and decompensated (generalized) forms are distinguished.

In the host organism, microorganisms exist in the intestinal lumen, on the surface of the epithelium, in crypts. As was shown in an experiment on animals, initially there is "sticking" (adhesion) of the microorganism to the surface of the enterocyte. After adhesion, proliferation of microbial cells and release of enterotoxin are observed, which causes a violation of water-electrolyte metabolism, the appearance of diarrhea, leading to dehydration and death of the animal. "Adhesion" of microorganisms, in particular Escherichia coli, is facilitated by the specific adhesive factors they produce, which include K-antigens or capsular antigens of protein or polysaccharide nature, providing microorganisms with a selective ability to attach to the surface of the mucous membrane. Excessive secretion of fluid under the action of endotoxin produced by a bacterial cell is considered not only as a manifestation of a pathological process in the small intestine, but also as a protective mechanism that helps flush out microorganisms from the intestine. Specific antibodies and leukocytes participate in the body's immune reactions, as shown by studies obtained on the Thiry-Vella loop.

With dysbacteriosis, the antagonistic function of normal intestinal microflora in relation to pathogenic and putrefactive microbes, the vitamin-forming and enzymatic function are disrupted, which cannot but affect the general condition of the body due to a decrease in its resistance.

By affecting the normal functional activity of the digestive tract, the altered microflora leads to the formation of toxic products that are absorbed in the small intestine. A certain role of intestinal bacteria in the development of colon cancer in humans has been proven, and the participation of various bacterial metabolites is ambiguous. Thus, amino acid metabolites take little part in oncogenesis, while the role of bile acid metabolites produced by nuclear dehydrogenase and 7-dehydroxylase in this process is very significant. It has been established that the concentration of bile acids in feces in various population groups on different continents correlates with the risk of colon cancer, and most people from groups with a high risk of colon cancer have clostridia in the intestine that have the ability to produce nuclear dehydrogenase beta-hydroxysteroid-4,5-dehydrogenase). In the group of people with a low risk, they are rarely detected. Clostridia are also found in the feces of a higher proportion of colon cancer patients compared with controls.

In weakened, exhausted, sick children, especially those who have suffered from any diseases, there is an intensive reproduction of opportunistic microflora, which is a permanent inhabitant of the intestines of humans and animals (for example, representatives of the genus Escherichia), which can lead to the development of infectious processes and even sepsis. Often, in dysbacteriosis, microorganisms resistant to widely used antibacterial drugs predominate, which have the ability to spread in the population of closely related associations. Similar conditions allow the predominant spread of coccal flora, putrefactive microorganisms (genus Proteus, etc.), fungi (usually of the Candida type), Pseudomonas bacteria, which often cause the development of postoperative complications. The most common dysbacteriosis is fungal, staphylococcal, proteus, pseudomonas, caused by Escherichia and various associations of the indicated microorganisms.

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Diagnostics intestinal dysbiosis

Laboratory data

1. Microbiological examination of feces - a decrease in the total number of E. coli, bifido- and lactobacilli is determined; pathogenic microflora appears.
2. Coprocytogram - a large amount of undigested fiber, intracellular starch, steatorrhea (soaps, fatty acids, rarely - neutral fat) are determined.
3. Biochemical analysis of feces - with dysbacteriosis, alkaline phosphatase appears, the level of enterokinase increases.
4. Positive hydrogen breath test - bacterial overgrowth in the small intestine results in a sharp increase in hydrogen content in exhaled air after lactulose loading.
5. Culture of jejunal aspirate for bacterial flora - intestinal dysbacteriosis is characterized by the detection of more than 1010 microorganisms in 1 ml. The diagnosis of dysbacteriosis is especially likely in the presence of obligate anaerobes (clostridia and bacteroides), facultative anaerobes or intestinal bacteria.
6. Examination of the jejunal biopsy reveals flattening of the villi and leukocyte infiltration of the lamina propria of the mucous membrane.

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Treatment intestinal dysbiosis

Treatment of dysbacteriosis should be comprehensive, and along with the impact on the underlying disease and increasing the body's resistance, it involves the administration of drugs, the type of which depends on the nature of changes in the intestinal microbial flora. If pathogenic or opportunistic microorganisms are detected, a course of treatment with antibacterial drugs is administered.

Ampicillin and carbenicillin have a selective effect on the Proteus group and a number of strains of Pseudomonas aeruginosa. In recent years, antibiotic synergists have been combined. Thus, in staphylococcal dysbacteriosis, a combination of aminoglycosides (kanamycin, gentamicin sulfate, monomycin) with ampicillin is especially effective; in the presence of Pseudomonas aeruginosa - gentamicin sulfate with carbenicillin disodium salt; polymyxin, Pseudomonas bacteriophage. Tetracycline, chloramphenicol, erythromycin, lincomycin, clindamycin affect anaerobic and aerobic flora.

Nitrofuran derivatives, sulfonamides and preparations created on the basis of their combination with trimethoprim - biseptol can be used in combination with antibiotics or independently. It has been established that sulfonamide preparations are well absorbed, remain in the body for quite a long time in the required concentration, do not suppress the normal microflora of the intestine and respiratory tract.

To treat candidal dysbacteriosis, fungicidal antibiotics are used - nystatin, levorin, and in severe cases - amphoglucamine, decamin, amphotericin B.

For proteus dysbacteriosis, nitrofuran series drugs are recommended - furacrilin, furazolin, furazolidone, as well as coliproteus bacteriophage, derivatives of 8-oxyquinoline (5-NOC, enteroseptol) and nalidixic acid (negram). Negram is also highly effective in severe, intractable intestinal dysbacteriosis caused by a microbial association of bacteria of the genus Proteus, staphylococci, lactose-negative Escherichia, yeast-like fungi.

Previously, mexaform and mexaza were prescribed to normalize intestinal microflora, which were effective in chronic enteritis and colitis complicated by dysbacteriosis. However, recently, due to the side effects of these drugs, often caused by their excessively long and uncontrolled use, the production and use of these drugs have sharply decreased.

Currently, after taking antibiotics and other antibacterial agents for the treatment of dysbacteriosis, colibacterin, bifidumbacterin, bificol, lactobacterin are indicated, i.e., drugs obtained from representatives of the normal intestinal microflora of a person and successfully used for dysbacteriosis in various intestinal diseases. All these drugs or one of them can be recommended without a preliminary course of antibacterial therapy if dysbacteriosis is manifested only by the disappearance or decrease in the number of representatives of the normal intestinal flora.

Antagonistic activity of these preparations against pathogenic and opportunistic intestinal bacteria has been noted. Therefore, in a number of cases, when staphylococcus, fungi and other foreign inhabitants are found in the intestine in small quantities, only bacterial preparations containing full-fledged normal microflora are sufficient.

If dysbacteriosis is accompanied by a digestive disorder, it is advisable to use enzyme preparations (festal, panzinorm, etc.). If dysbacteriosis is caused by excessive, insufficiently justified or uncontrolled use of antibacterial agents, primarily antibiotics, then after their withdrawal, desensitizing, detoxifying and stimulating therapy is carried out. Antihistamines, hormonal drugs, calcium preparations, pentoxyl, methyluracil, vitamins, blood transfusions, gamma globulins, vaccines, anatoxins, bacteriophages, lysozyme, specific antistaphylococcal and antipseudomonal serums, eubiotics and bacterial preparations are prescribed.

In case of decompensated dysbacteriosis complicated by sepsis, levamisole, taktivin, antistaphylococcal plasma, antistaphylococcal immunoglobulin, blood transfusion, red blood cell mass, protein, hemodesis, rheopolyglucin, electrolyte solutions, and vitamins are indicated.

Prevention

The basis for the prevention of dysbacteriosis is the observance of hygiene rules, adequate nutrition of patients, especially weakened ones, general strengthening measures, the prescription of antibacterial drugs only for strict indications. Antibiotics should be combined with vitamins (thiamine, riboflavin, pyridoxine, vitamin K, ascorbic and nicotinic acids), which have a beneficial effect on the functional state of the intestine and its microflora, as well as with enzyme preparations, which prevents the occurrence of intestinal dysbacteriosis.

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