Dysbacteriosis of the intestine

Dysbacteriosis of the intestine - a change in the qualitative and quantitative composition of the bacterial flora, caused by a dynamic violation of the microecology of the intestine as a result of disruption of adaptation, violation of the protective and compensatory mechanisms of the body.

[1], [2], [3], [4], [5], [6], [7]

Epidemiology

Dysbacteriosis of the intestine is very common. It is detected in 75-90% of cases of acute and chronic gastroenterological diseases.

[8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]

Causes of the intestinal dysbiosis

The most frequent and actual causes of intestinal dysbiosis are the following:

1. Antibiotic-chemotherapy, the use of glycocorticoids, cytostatics.
2. Professional long-term contact with antibiotics.
3. Acute and chronic diseases of the gastrointestinal tract of infectious and non-infectious nature. The main role in the development of dysbiosis in this situation plays a conditionally pathogenic flora.
4. Changes in the primary diet, the abuse of sucrose.
5. Severe diseases, surgical interventions, mental and physical stress.
6. Long stay of a person in uncharacteristic for him (unusual) habitats, extreme conditions (speleological, high altitude, Arctic expeditions, etc.).
7. Immunodeficiency states (with oncological diseases, HIV infection).
8. The effect of ionizing radiation.
9. Anatomical-physical disorders of the intestine: anatomical abnormalities, complications during operations on the gastrointestinal tract, intestinal motility disorders and absorption of nutrients. Syndromes malabsorption and maldigestii create favorable conditions for reproduction of conditionally pathogenic flora.
10. Polyhypovitaminosis.
11. Starvation.
12. Gastrointestinal bleeding.
13. Food allergy.
14. Fermentopathy (congenital and acquired), intolerance of various foods, including whole milk (lactase deficiency); cereals (gluten entero-patia), fungi (trehgalaznaya insufficiency).

Under the influence of etiological factors there is a qualitative and quantitative change in the intestinal microflora. As a rule, the number of basic bacterial symbionts of the intestine - bifidobacteria, lactic acid and non-pathogenic E. Coli, is significantly reduced. Along with this, the number of conditionally pathogenic microbes (enterobacteria, staphylococcus, etc.), fungi of the genus Candida, 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 the dysbiosis microbial associations do not perform protective and physiological functions and disrupt the functioning of the intestine.

Heavy forms of dysbiosis cause significant disturbances in the digestive and absorption functions of the intestine and sharply disrupt the general state of the body. Conditionally pathogenic bacteria, in excess of colonizing the intestine, disrupt the absorption of carbohydrates, fatty acids, amino acids, vitamins. Metabolism products (indole, skatole, etc.) and toxins produced by the conditionally pathogenic flora reduce the detoxification function of the liver, increasing the symptoms of intoxication.

[21], [22], [23], [24], [25]

Pathogenesis

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

The intestinal microflora is subdivided into the obligate microorganisms (microorganisms that constantly form part of normal flora and play an important role in metabolism and anti-infective protection) and optional (microorganisms often found in healthy people, but are conditionally pathogenic, i.e., capable of causing diseases with a decrease resistance of the macroorganism).

The dominant representatives of obligate microflora are non-sporeforming anaerobes: bifido- and lactobacilli, bacteroides. Bifidobacteria constitute 85-98% of the intestinal microflora.

Functions of normal intestinal microflora

• creates an acidic environment (pH of the medium of the colon to 5.3-5.8), which prevents the propagation of pathogenic, putrefactive and gas-forming microflora of the intestine;
• promotes the enzymatic digestion of food ingredients (bifido- and lactobacilli, eubacteria, bacteroids increase the hydrolysis of proteins, saponify fats, ferment carbohydrates, dissolve the cellulose);
• performs 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 lactobacillus 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 immunological resistance of the body (bifido- and lactobacilli stimulate the function of lymphocytes, the synthesis of immunoglobulins, interferon, cytokines, increase the level of complement, lysozyme activity);
• enhances the physiological activity of the gastrointestinal tract, in particular, intestinal motility;
• stimulates the synthesis of biologically active substances, positively affecting the function of the gastrointestinal tract, cardiovascular system, hematopoiesis;
• plays an important role in the final stages of the metabolism of cholesterol and bile acids. In the large intestine, with the participation of bacteria, cholesterol is converted into sterol coprostanol, which is not absorbed. With the help of the microflora of the intestine, hydrolysis of the cholesterol molecule also occurs. Under the influence of microflora enzymes, bile acid changes occur: deconjugation, conversion of primary bile acids into keto derivatives of cholanic acid. Normally about 80-90% of bile acids are reabsorbed, the rest of them is excreted with feces. The presence of bile acids in the large intestine slows the absorption of water. The activity of microflora promotes the normal formation of feces.

Obligatnaya microflora in healthy people is constant, performs the leading biological functions, useful for the human body (bifido- and lactobacilli, bacteroides, intestinal bacteria, enterococci). The facultative microflora is variable, its species composition varies, it is quickly eliminated, does not have a significant effect on the host's organism, since its contamination is low (opportunistic bacteria - citrobacter, micrococci, pseudomonas, proteus, yeast-like fungi, staphylococcus, clostridia, etc.).

Quantitative composition of normal intestinal microflora

Name of microorganisms	CFU / g of feces
Bifidobacteria	108-1010
Lactobacilli	106-1011
Bacteroides	107-109
Peptococci and Peggostreptococci	105-10b
Escherichia	10b-108
Staphylococci (hemolytic, plasma-coagulating)	Not more than 103
Staphylococci (hemolytic, epidermal, coagulase negative)	- 104-105
Streptococci	105-107
Clostridia	103-105
Eubacteria	10Z-1010
Yeast-eating mushrooms	Not more than 10Z
Conditionally pathogenic enterobacteria and nonfermentative gram-negative rods	Not more than 103-104

Note. CFU - the number of colony forming units

Gastrointestinal tract is a natural habitat for microorganisms in humans and animals. Especially a lot of microorganisms in the lower part 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 thin there is much less due to bactericidal gastric juice, peristalsis and, probably, endogenous antimicrobial factors of the small intestine. In the upper and middle section of the small intestine there are only small populations, mainly gram-positive facultative aerobes, a small amount of anaerobes, yeasts and fungi. In the distal parts of the small intestine (in the area of the ileocecal damper), the "microbial spectrum" has an intermediate position between the microflora of the proximal parts of the small and large intestine. The lower part of the ileum is inhabited by the same microorganisms that are in the large intestine, although they are smaller. More accessible to the study of fecal microflora, which is actually the flora of the distal colon. The appearance of long intestinal probes made it possible to examine the microflora throughout the entire gastrointestinal tract.

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

In faeces, microscopy reveals a number of bacterial cells, of which about 10% can multiply on artificial nutrient media. In healthy individuals, about 95-99% of microorganisms that can be cultivated are anaerobes, which are represented by bacterioids (10 ⁵ -10 ¹² per 1 g of feces) and bifidobacteria (10 ⁸ -10 ¹⁰ bacterial cells per 1 g of stool). The main representatives of aerobic fecal flora are E. Coli (10 ⁶ -10 ⁹ ), enterococcus (10 ³ -10 ⁹ ), lactobacilli (up to 10 ¹⁰ ). In addition, fewer and fewer are detected staphylococci, streptococci, clostridia, klebsiella, proteus, yeast-like fungi, protozoa, etc.

Usually, in a bacteriological study, the feces of a healthy person pay attention not only to the total amount of E. Coli (300-400 ppm), but also to its content with slightly expressed enzymatic properties (up to 10%), as well as lactosonegative 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, hemolyzing E. Coli, hemolyzing staphylococcus, protea, fungi of the genus Candida and other bacteria in the feces of a healthy person should not be.

Normal microflora, being a symbiont, performs a number of functions that are essential for the life of a macroorganism: nonspecific protection against bacteria that cause intestinal infections, based on microbial antagonism, participation in the production of antibodies, and vitamin-synthesizing function of microorganisms, in particular vitamins C, K, B1, B2, Вб, В12, PP, folic and pantothenic acids. In addition, microorganisms inhabiting the intestine break down cellulose; participate in the enzymatic cleavage of proteins, fats and high-molecular carbohydrates; promote the absorption of calcium, iron, vitamin D through the creation of an acidic environment; take part in the exchange of bile acids and the formation in the large intestine of sterocilin, coprosterol, deoxycholic acid; inactivate enterokinase and alkaline phosphatase; participate in the formation of protein decay products (phenol, indole, scatol), 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 vary under the influence of various pathological processes or exogenous factors, which is manifested by a violation of the normal relationships between different types of microorganisms and their distribution in different parts of the intestine. The appearance of an altered dysbiotic microflora characterizes a condition called dysbacteriosis. With pronounced dysbacteriosis, the number of microorganisms in the small intestine increases, with the predominance of bacteria of the genus Escherichia, Klebsiella, lactobacillus, campylobacteria and enterococcus. In the large intestine and bowel movements, the number decreases or bifidobacteria completely disappear, the number of Escherichia, Staphylococcus, Streptococcus, Yeast, Klebsiella, Protea increases.

Dysbacteriosis is most often manifested by a decrease in the total number of microorganisms, sometimes until the complete disappearance of individual species of normal microflora with the simultaneous predominance of species that are normally present in a minimal amount. This predominance can be prolonged or occur periodically. In the emergence of dysbiosis an essential role is played by the antagonistic relationships of representatives of natural associations. Small temporal fluctuations in the number of individual microorganisms are eliminated on their own without any intervention. The conditions under which the rate of reproduction of some representatives of microbial associations increases or specific substances that inhibit the growth of other microorganisms accumulate significantly change the composition of the microflora and the quantitative ratio of various microorganisms, ie, there is a dysbacteriosis.

With various diseases, the small intestine is filled with microorganisms from the distal parts of the intestine, and then the microflora in it resembles the "microbial landscape" of the large intestine.

[26], [27], [28], [29], [30], [31], [32], [33], [34], [35]

Symptoms of the intestinal dysbiosis

In many patients, the intestinal dysbacteriosis is latent and is recognized by bacteriological study of feces. Clinically expressed forms of dysbacteriosis are characterized by the following symptoms:

• diarrhea - loose stools can occur 4-6 or more times; in a number of cases, the consistency of the feces is pulp-like, in the feces the pieces of undigested food are determined. Diarrhea is not a necessary symptom of intestinal dysbiosis. Many patients have diarrhea, there can only be unstable stools;
• flatulence - a fairly constant symptom of dysbiosis;
• pain in the abdomen of a fickle, uncertain nature, usually of medium intensity;
• malabsorption syndrome develops with prolonged and severe course of dysbiosis;
• bloating, rumbling during palpation of the terminal segment of the iliac and, more rarely, of the caecum.

[36], [37], [38], [39], [40], [41], [42]

Stages

The degree of dysbiosis can be judged by the classification:

• 1 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 laktooflora not changed. As a rule, there is no intestinal dysfunction.
• 2 degree (subcompensated form) - against a background of insignificant decrease in the content of bifidobacteria, quantitative and qualitative changes in Escherichia and an increase in the population level of a group of opportunistic bacteria, pseudomonads and fungi of the genus Candida are revealed.
• 3 degree - a 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 aggressive properties of opportunistic microorganisms. As a rule, with dysbacteriosis of the 3rd degree there is dysfunction of the intestine.
• 4 degree - the absence of bifidoflora, a significant decrease in the amount of lactoflora and changes in the content of Escherichia coli (decrease or increase), an increase in the number of obligate, facultative and non-typical species of opportunistic microorganisms in associations. The normal ratio of the composition of the intestinal microbiocenosis is violated, as a result of which its protective and vitamin-synthesizing functions are reduced, the enzymatic processes are changing, the level of undesirable metabolic products of opportunistic microorganisms is increasing. In addition to dysfunction of the gastrointestinal tract, this can lead to destructive changes in the intestinal wall, bacteremia and sepsis, since the overall and local resistance of the organism decreases, and the pathogenic effect of opportunistic microorganisms is realized.

Some authors classify intestinal dysbiosis by the type of dominant pathogen:

1. staphylococcal;
2. klebsiellezny;
3. Protein;
4. bacteroid;
5. clostridiose (Cl. Difficile);
6. candidomycosis;
7. mixed.

Latent and subcompensated forms of dysbacteriosis are more typical for light and moderate forms of dysentery and salmonellosis, postdisenteric colitis. Decompensated dysbiosis is noted with a severe and protracted course of acute intestinal infections, concomitant pathologies of the gastrointestinal tract, as well as with ulcerative colitis, protozoal colitis.

Stages of dysbacteriosis can be determined using the classification:

• I stage - decrease in the amount or elimination of bifidobacteria and (or) lactobacilli.
• II stage - a significant increase in the subsequent prevalence of colibacterial flora or its sharp decline, atypical and enzymatically inferior E. Coli.
• III stage - high titers of the association of conditionally pathogenic microflora.
• IV stage - the bacteria predominate in the genus Proteus or Pseudomonas aeruginosa in high titers.

Of great interest is the classification of dysbiosis according to AF Bilibin (1967):

Dysbacteriosis of the intestine is usually a localized pathological process. However, in a number of cases, generalization of dysbacteriosis is possible. The generalized form is characterized by bacteremia, possibly the development of sepsis and septicopyemia.

Dysbacteriosis of the intestine can occur in latent (subclinical), local (local) and common (generalized) forms (stages). With latent form, a change in the normal composition of symbionts in the intestine does not lead to the appearance of a visible pathological process. With a local form of dysbiosis, an inflammatory process occurs in some organ, particularly in the intestine. Finally, with a common form of dysbiosis, 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 parenchymal ones, intoxication, and sepsis often occurs. Compensated, more often latently, subcompensated (as a rule, local) and decompensated (generalized) forms are allocated according to the degree of compensation.

In the host organism, microorganisms exist in the gut lumen, on the surface of the epithelium, in crypts. As was shown in the experiment on animals, "adhesion" (adhesion) of the microorganism to the surface of the enterocyte occurs first. After adhesion, the proliferation of microbial cells and the release of enterotoxin are observed, which causes disruption of water-electrolyte metabolism, the appearance of diarrhea leading to dehydration and death of the animal. The adhesion of microorganisms, in particular Escherichia coli, is promoted by the specific adhesive factors they produce, which include K-antigens or capsular antigens of protein or polysaccharide nature, which ensure that microorganisms are selectively able to attach to the mucosal surface. Excessive release of fluid under the action of endotoxin produced by the bacterial cell is considered not only as a manifestation of the pathological process in the small intestine, but also as a protective mechanism that facilitates the elution of microorganisms from the intestine. Specific antibodies and leukocytes are involved in the immune reactions of the body, as shown by studies on the Tiri-Vella loop.

With dysbacteriosis, the antagonistic function of the normal intestinal microflora is violated with respect to pathogenic and putrefactive microbes, a vitamin-forming and enzymatic function, which can not but affect the general state of the organism due to a decrease in its resistance.

Influencing 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 proved, and the participation of various bacterial metabolites is ambiguous. Thus, metabolites of amino acids take little part in oncogenesis, while the role of metabolites of bile acids produced by nuclear dehydrogenase and 7-dehydroxylase is very significant in this process. It was found that the concentration of bile acids in feces in various populations of different continents correlates with the risk of developing colon cancer, and in most people from groups with a high risk of colon cancer, there are clostridia in the intestine that have the ability to produce nuclear β-oxysteroid- 4,5-dehydrogenase). In the group of persons of low risk, they are rarely detected. Clostridia is also found in feces in the majority of patients with colon cancer as compared to the control group.

Weakened, malnourished, sick children, especially those suffering from any diseases, observe intensive propagation of opportunistic microflora, which is a permanent inhabitant of the intestine of humans and animals (for example, representatives of the genus Escherichia), which can lead to the emergence of infectious processes and even sepsis. Often, with dysbacteriosis, microorganisms that are resistant to widely used antibacterial drugs prevail, which have the ability to spread in a population of closely related associations. Similar conditions allow predominantly spreading cocco flora, putrefactive microorganisms (genus Proteus, etc.), fungi (more often of Candida type), bacteria Pseudomonas, often causing the development of postoperative complications. The most common dysbacteriosis fungal, staphylococcus, Proteus, Pseudomonas, caused by Escherichia and various associations of these microorganisms.

[43], [44], [45], [46], [47], [48], [49], [50]

Diagnostics of the intestinal dysbiosis

Laboratory data

1. Microbiological examination of feces - a decrease in the total amount of E. Coli, bifido- and lactobacilli is determined; there is a pathogenic microflora.
2. Coprocygram - a large amount of undigested fiber, intracellular starch, steatorrhea (soaps, fatty acids, rarely - neutral fat) is determined.
3. Biochemical analysis of feces - with dysbacteriosis, alkaline phosphatase appears, and the level of enterokinase increases.
4. Positive hydrogen respiratory test - excess bacterial growth in the small intestine leads to a sharp increase in the hydrogen content in the exhaled air after a load of lactulose.
5. Sowing of the lean gut aspirate on the bacterial flora - for the intestinal dysbacteriosis, more than 1010 microorganisms per ml are detectable. Diagnosis of dysbacteriosis is particularly likely in the presence of obligate anaerobes (clostridia and bacteroides), facultative anaerobes or bacteria of the intestinal group.
6. Examination of the jejunal biopsy specimen-flattening of villi and leukocyte infiltration of the propria of the mucous membrane are observed.

[51], [52], [53], [54], [55]

Treatment of the intestinal dysbiosis

Treatment of dysbiosis should be complex, and along with the impact on the underlying disease and increasing resistance of the organism, it provides for the appointment of funds, a variety of which depends on the nature of changes in the microbial flora of the intestine. When detecting pathogenic or conditionally pathogenic microorganisms, a course of treatment with antibacterial drugs is carried out.

Selective effect on the proteus group and a number of strains of Pseudomonas aeruginosa ampicillin and carbenicillin. In recent years, antibiotics-synergists have been combined. Thus, with staphylococcal dysbacteriosis, the combination of aminoglycosides (kanamycin, gentamycin sulfate, monomycin) with ampicillin is especially effective, in the presence of a pseudomonas aeruginosa - gentamycin sulfate with carbenicillin disodium salt; polymyxin, pseudomonas bacteriophage. Anaerobic and aerobic flora is affected by tetracycline, chloramphenicol, erythromycin, lincomycin, clindamycin.

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

For the treatment of candidal dysbiosis use fungicidal antibiotics - nystatin, levorin, and in severe course - amphoglucamine, dekamine, amphotericin B.

Protein dysbacteriosis recommends drugs of the nitrofuran series - furacrylin, furazoline, furazolidone, as well as coliprotein bacteriophage, derivatives of 8-hydroxyquinoline (5-NOK, enterosettopol) and nalidixic acid (blacks). Negro is highly effective in case of severe intractable dysbiosis due to microbial association of bacteria of the genus Proteus, Staphylococci, Lactose-negative Escherichia, yeast-like fungi.

Earlier, for normalization of the intestinal microflora, mexamens and mexazas were prescribed, which were effective for chronic enteritis and colitis complicated by dysbiosis. However, recently, in connection with the side effects of these drugs, more often due to excessively long and uncontrolled reception, the production and use of these drugs have declined sharply.

Currently, after taking antibiotics and other antibacterial agents for the treatment of dysbacteriosis, colibacterin, bifidumbacterin, bifikol, lactobacterin are shown, ie, preparations obtained from representatives of normal intestinal microflora of the person and successfully used for dysbiosis in various bowel diseases. All these drugs or one of them can be recommended without a prior course of antibiotic therapy, if the dysbacteriosis manifests itself only by the disappearance or decrease in the number of representatives of the normal intestinal flora.

The antagonistic activity of these drugs in relation to pathogenic and opportunistic intestinal bacteria was noted. Therefore, in a number of cases, when staphylococcus, fungi and other foreign inhabitants are found in the intestine in a small amount, only bacterial preparations containing a normal normal microflora are sufficient.

If the dysbacteriosis is accompanied by a violation of digestion, it is advisable to use enzyme preparations (festal, panzinorm, etc.). If the dysbacteriosis is caused by excessive, insufficiently justified or uncontrolled use of antibacterial agents, primarily antibiotics, then after their cancellation, desensitizing, detoxifying and stimulating therapy is performed. Prescribe antihistamines, hormonal drugs, calcium preparations, pentoxyl, methyluracil, vitamins, blood transfusions, gamma globulins, vaccines, anatoxins, bacteriophages, lysozyme, specific antistaphylococcal and antisseudomonal sera, eubiotics and bacterial preparations.

In case of decompensated dysbacteriosis complicated with sepsis, levamisole, tactivin, antistaphylococcal plasma, antistaphylococcal immunoglobulin, blood transfusion, erythrocyte mass, protein, hemodex, rheopolyglucin, electrolyte solutions, vitamins are shown.

Prevention

The basis for the prevention of dysbiosis is the observance of hygiene rules, adequate nutrition of patients, especially weakened, restorative measures, the appointment of antibacterial drugs only on strict indications. Antibiotics should be combined with vitamins (thiamin, riboflavin, pyridoxine, vitamin K, ascorbic and nicotinic acids), which favorably affect the functional state of the intestine and its microflora, as well as with enzyme preparations, which prevents the occurrence of intestinal dysbiosis.

[56], [57], [58], [59], [60], [61], [62], [63]