Bacteria in the small intestine symptoms. Bacterial overgrowth syndrome in the intestine: what is it, treatment, symptoms, causes, signs

The gastrointestinal tract of the body is seeded with several hundred different types of bacteria. The composition of microorganisms varies in sections more or less remote from the median plane of the small intestine. The microflora is of great importance for the normalization of the smooth functioning of the intestines. For a person without deviations in health, as a rule, various microorganisms serve to maintain the acid-base balance in the stomach in a normal state, contribute to the production of gastric juice for food processing, and control the motor activity of the small intestine. In the event of a failure in the operation of at least one of these devices, there is a high probability of the formation of bacterial overgrowth syndrome in the small intestine.

Definition

Excessive bacterial growth in the small intestine occurs as a result of changes associated with human anatomy, or in violation of the motor activity of the gastrointestinal tract and insufficiency of gastric secretion. The resulting violations can lead to nutritional problems, a loss of vitamins and failures in the digestion of fats. The syndrome of bacterial redundancy is treated with the use of antibacterial drugs.

Symptoms

Bloating is one of the symptoms of the disease.

Patients with bacterial overgrowth syndrome experience the following symptoms:

• painful bloating, rumbling, which occur a short time after eating;
• mainly diarrhea;
• poorly digested food in feces;
• the presence of blotches of fat in the feces;
• decreased vision;
• in rare cases, nausea is observed;
• prostration;
• headaches;
• sharp weight loss;
• feeling of anxiety, panic;
• predominantly bad mood;
• dizziness;
• depressive state.

Forms of the disease

The bacterial increase in the small intestine depends on the amount and nature of the microflora and can be of three degrees:

1. The first degree is aerobic, i.e., to perform the vital functions of a group of living organisms, invisible to the naked eye, oxygen is needed, with an increased intestinal microflora.
2. The second degree in the syndrome is an aerobic intestinal increased microflora with the formation of bacteria. In this case, oxygen is not required to perform the vital functions of microorganisms.
3. The third degree has the majority of anaerobic microflora.

The source of the disease

Small intestine with bacterial overgrowth syndrome is a phenomenon that can occur for a number of reasons. Basically, the causes are divided into those that study the origin of the disease, their conditions, as well as those that are based on the study of the development of the disease.

Possible cause of bacterial growth.

According to the etiology, the following causes of bacterial growth are distinguished:

• an excess level of bacteria in the intestine may occur after operations;
• violations in the functionality of the Bauginian damper;
• diseases of the digestive system that are associated with intestinal motility;
• prolonged eating disorder;
• damage in the intestinal cavity under the influence of enzymes of digestion and absorption;
• the structure of the intestine, namely the narrowing of its lumen;
• various food intolerances;
• inflammatory diseases of the chronic form in the intestine;
• obstruction;
• symptom complex of chronic disorders;
• diverticular disease;
• cirrhosis of the liver;
• alcoholism;
• vagatomy;
• prolonged use of medications that reduce the human immune system;
• excessive antibiotic therapy;
• bacteria that come from the extraintestinal receptacle;
• all kinds of stress;
• disorders of the immune system of a local and systemic nature;
• diabetes.

As a result of exposure to etiological signs, there is a violation of the protective layer of the mucous membrane of the small intestine. As a result, local and systemic processes of pathology are caused, the protective purpose of the mucous membrane and the functioning of digestive enzymes are disrupted. In addition, there is a disorder of secretion, oxidation of fatty acids, endogenous intoxication.

With serious violations of the human immune system, an exchange of bacteria into the lymph and blood can occur, followed by the development of inflammation with pus on various tissues and organs.

Diagnosis and treatment

Diagnosis allows you to make an accurate diagnosis and state the excessive bacterial growth. Thus, the diagnosis may include:

• Collection of information about the patient's family in order to identify the presence of diseases associated with the digestive system by family ties.
• Analysis of the patient's complaints and past illnesses, as well as the study of the patient's stool (consistency, duration). In addition, flatulence, nausea are taken into account.
• Visual examination of the patient, which is based on an assessment of the patient's skin color, physique and determination of the presence of excess weight.
• Collection of information about existing diseases of the gastrointestinal tract and past operations and other diseases.

The Schilling test detects B12 deficiency anemia.

Diagnosis without fail includes laboratory tests, which are based on donating blood for a general analysis, which will show or refute anemia, an increase in the level of leukocytes, which happens during an inflammatory process in the body. In addition, a biochemical blood test should be performed, which will reveal the root cause of the disease, a general urine test, which is necessary to determine the increase in possible chemicals that indicate the development of excess bacteria. To make an accurate diagnosis and determine the root cause, it is important to conduct an analysis of the channel, which will indicate the presence or absence of undigested food, determine the acidity of the stool and the amount of fat in it.

An important research method is the breath test. Before carrying out which you should follow a number of rules: it is forbidden to eat food with the presence of carbohydrates in the evening before testing; do not smoke and do not overload the body with physical activity a few hours before the test; rinse the mouth with antibacterial action before proceeding with the test. Another equally important diagnostic method is the sugar test, which will show hydrogen in bacterial growth, as well as the xylose test, which is necessary to detect labeled carbon dioxide.

Diagnosis of bacterial overgrowth syndrome is based on an instrumental study:

• X-ray, which is needed to detect diverticulosis, or narrowing of the small intestine.
• The Schilling test, which consists in taking vitamin B12 by the patient and after which it is excreted in the urine. The doctor evaluates the absorption of the vitamin.
• Biopsy of the small intestine. To do this, a piece of tissue is taken and sent for examination under a microscope. If the diagnosis of the disease is confirmed, an abnormal change in the intestinal mucosa occurs.

In case of excessive growth of bacteria, the following specialists should be consulted:

• a surgeon who will rule out surgical pathologies;
• gynecologist - necessary to exclude pathologies of a gynecological nature;
• urologist, consultation with which will exclude urinary pathologies;
• an infectious disease specialist, consultation with whom is carried out if indicated and is necessary to exclude infectious diarrhea.

Non-drug treatment consists in observing the necessary diet.

Treatment of increased bacterial growth in the small intestine is based on the reduction or complete elimination of the symptoms of the primary disease, the elimination of the excessive presence of bacteria in the small intestine, the restoration of microbiocenosis and the normalization of the functioning of the digestive system. Therapy can be carried out with or without medication.

Non-drug treatment consists in following the necessary diet and eating foods of natural origin. Such products include fermented milk products with bifidobacteria. Treatment of the syndrome with drugs is based on therapy with antibacterial drugs, probiotics, prebiotics. If necessary, intravenous vitamin therapy is prescribed.

Surgical intervention is performed in case of ineffective drug and non-drug treatment.

For citation: Plotnikova E.Yu., Zakharova Yu.V. Diagnosis and treatment of bacterial overgrowth syndrome. 2015. No. 13. S. 767

The human gastrointestinal tract (GIT) is normally inhabited by 300 to 500 different types of bacteria. The microbial landscape is significantly different in the proximal and distal small intestine. If approximately 102 colony forming units / ml (CFU / ml) live in the upper sections of the small intestine, then closer to the large intestine there are already 109 CFU / ml.

In the proximal small intestine, Gram-positive aerobic bacterial species are most common, while Gram-negative anaerobic bacteria are more common in the distal intestine. The mass of the normal intestinal microflora of an adult is more than 2.5 kg, the number is 1014 CFU, and the total genome of bacteria - the "microbiome" - includes 400 thousand genes, which is 12 times more than the human genome. In healthy individuals, the normal gut microflora is maintained by such basic physiological mechanisms as the pH level of hydrochloric acid in the stomach, pancreatic secretory activity and choleresis, small intestinal motility, and the structural integrity of the gastrointestinal tract. Disruption of any of these defense mechanisms can lead to the development of bacterial overgrowth syndrome (SIBO) in the small intestine.

There are a number of factors that allow maintaining the quantitative and species constancy of the microbial landscape of the human intestine:

• genetic predisposition;
• acidic gastric environment;
• normal motor-evacuation function of the gastrointestinal tract;
• anatomical sphincters of the gastrointestinal tract;
• constant level of intraluminal pH in different biotopes;
• the state of the immune system of the mucous membranes (SO);
• bactericidal substances produced by CO (lysozyme, lactoferrin, etc.);
• phagocytic activity of CO macrophages;
• secretory immunoglobulin class A;
• bacterial colicins and microcins (endogenous peptide antibiotics of microbial origin).

SIBO in the small intestine is understood as a pathological condition, which is based on an increased colonization of the small intestine with fecal or oropharyngeal microflora, accompanied by chronic diarrhea and malabsorption, primarily of fats and vitamin B12. An increase in the number of opportunistic microflora in the small intestine is detected in 70–95% of cases of chronic intestinal pathology. With SIBO, not only the number increases, but also the spectrum of microorganisms changes with a shift towards gram-negative bacteria and anaerobes. In 30% of healthy people, the jejunum is normally sterile, in the rest it has a low population density, which increases as it approaches the colon, and only in the distal ileum is the fecal microflora found: enterobacteria, streptococci, anaerobes of the bacteroid genus, etc.

The most important etiological factors for SIBO include:

• dysfunction of the ileocecal valve (inflammatory, tumor processes, primary functional failure);
• consequences of surgical operations (anatomical or surgically formed blind loop; small-colonic anastomosis or fistula, vagotomy, cholecystectomy, resection of the small intestine);
• diseases of the gastrointestinal tract associated with motor disorders: gastrostasis, duodenostasis, stasis of the contents in the small and large intestines (chronic constipation, including in diabetic patients);
• disorders of abdominal digestion and absorption (maldigestion and malabsorption), including those associated with achlorhydria of various origins (operated stomach, chronic atrophic gastritis, long-term use of proton pump inhibitors (PPI)), exocrine pancreatic insufficiency (chronic pancreatitis), biliary tract pathology ways (cholelithiasis, chronic cholecystitis);
• enteropathy (disaccharidase deficiency and other food intolerances);
• prolonged nutritional imbalance;
• chronic inflammatory bowel disease, diverticulitis, short bowel syndrome;
• intake of bacteria from an extraintestinal reservoir (for example, with cholangitis);
• local and systemic immune disorders - radiation, chemical effects (cytostatics), AIDS;
• antibiotic therapy;
• stresses of various origins;
• tumors of the intestine and mesenteric lymph nodes.

Various diets for weight loss, “cleansing” with the use of voluminous enemas, and especially hydrocolonotherapy, which has a certain popularity, but is strongly not recommended by gastroenterologists around the world, have a negative impact on the microbial landscape of the intestine, because it grossly violates microbial biotopes.

Characterization of SIBO requires not only counting the absolute number of bacteria, but also their species typing, which determines the manifestation of signs and symptoms. If overgrowth of bacteria that metabolize bile salts into unconjugated or insoluble compounds predominates, fat malabsorption or bile acid diarrhea develops. Deconjugated bile acids can have a toxic damaging effect on enterocytes, which disrupts the assimilation of not only fats, but also carbohydrates and proteins. With an overgrowth of bacteria that preferentially metabolize carbohydrates into short-chain fatty acids and gas, bloating without diarrhea predominates in the clinic, since the resulting metabolic products can be absorbed. Gram-negative coliforms such as Klebsiella produce toxins that damage the intestinal mucosa, impair absorption, and increase secretion.

Symptoms of SIBO are not specific: flatulence, bloating, abdominal pain or discomfort, diarrhea, fatigue, weakness, weight loss; they reflect the prevalence of inflammation of the intestinal mucosa, are superimposed on the manifestations of the underlying disease, which is the cause of the development of SIBO. More severe symptoms indicate complications of SIBO, including malabsorption, nutrient deficiencies, and bone metabolism disorders. The nonspecificity of these symptoms is often the cause of diagnostic errors and requires a differential diagnosis with irritable bowel syndrome, lactose intolerance, or fructose intolerance.

SIBO should be considered in every patient with diarrhea, steatorrhea, weight loss, and macrocytic anemia who complains of flatulence, cramping abdominal pain, and erratic bowel function, as well as chronic cytolysis syndrome.

Verification of excessive bacterial growth in the small intestine is carried out using direct and indirect methods for diagnosing this syndrome. The “gold standard” for diagnosing SIBO is culture of microflora; this requires aspiration of the contents of the small intestine with immediate inoculation of the aspirate on a nutrient medium. But bacterial overgrowth can affect the most distal portions of the small intestine, which are out of reach of the instrumentation.

Stool culture, which is used in our country as a method for assessing the microbial biocenosis of the intestine, is recognized as uninformative, because even with the maximum observance of the rules for conducting microbiological studies, it can give an idea of ​​only 12–15 types of bacteria of the distal colon. The study of feces can be used to search for specific infectious pathogens or helminthic invasion.

There are other methods based on the study of the concentration of indican produced by indole-positive microorganisms, phenol and paracresol, which are metabolites of aerobic (to a lesser extent) and anaerobic (to a greater extent) microorganisms, as well as a method for diagnosing the state of microbiocenosis of various biotopes, incl. intestine, based on the determination of short-chain (monocarboxylic) fatty acids, which are metabolites mainly of anaerobic genera of microorganisms, by gas-liquid chromatographic analysis. Indirect methods include tests based on the study of microflora metabolites: 14C- or 13C-glycocholate, 14C-D- or 13C-D-xylose breath tests, which require isotopes and a specialized laboratory. The most used worldwide are the hydrogen breath tests with lactulose (LVDT), glucose, lactose and other sugars.

Hydrogen breath tests are simple, informative and non-invasive methods that have been developed to diagnose various diseases of the alimentary canal, primarily to determine carbohydrate malabsorption and bacterial overgrowth in the small intestine. Currently, these diagnostic methods are rapidly being introduced into clinical practice all over the world.

In 2008, the Rome Consensus on Hydrogen Tests was adopted, which sets out the recommendations of international experts for clinical practice regarding the indications and methods for performing H2 breath tests in diseases of the alimentary canal. However, many practicing physicians not only do not know the main provisions of the consensus, but are still not familiar with these tests at all, do not know their diagnostic capabilities, certain limitations and shortcomings.

Hydrogen breath tests using carbohydrates (glucose, lactulose, fructose, lactose, etc.) have been performed since the 1970s. In one of the studies of J.M. Rhodes, P. Middleton, D.P. Jewell studied LVDT as a diagnostic test for SIBO, using the C14-glycocholate breath test as a comparison. PVDT was positive in 8 out of 9 patients, they also had a positive C14-glycocholate test, but in another 6 patients with a positive C14-glycocholate test, PVDT was negative. Subsequent bacteriological examination of duodenal juice for bacterial overgrowth in these patients was also negative. Negative PVDT results were obtained in 12 patients, none of whom subsequently developed bacterial overgrowth. LVDT is a simple and promising diagnostic test for detecting bacterial overgrowth in the small intestine. Unlike the C14-glycocholate test, the LVDT makes it possible to detect bacterial overgrowth in various parts of the small intestine.

The lactulose test is the most common non-invasive test for determining the intestinal transit time of various carbohydrates. An early peak in H2 concentration indicates SIBO, a delay in the growth of H2 concentration indicates a prolongation of intestinal transit time. This test is now used by all leading clinics in the world for the timely detection of SIBO in the small intestine.

In our work, in choosing a diagnostic algorithm for SIBO, we adhere to the following principles proposed by D. Drossman:

• determine if the patient has a clinical profile of small intestinal bacterial overgrowth with postprandial abdominal discomfort, bloating, and possibly loose stools;
• if clinical signs are present, test with LVDT (if available);
• if the result of LVDT is positive, prescribe an antibiotic or a broad-spectrum enteroseptic;
• after this treatment, prescribe a probiotic to the patient in order to restore the deficiency of “good” bacteria;
• if stool normalizes or constipation tends to develop, consider including prokinetics to promote intestinal transit;
• if symptoms recur and previous PVDT was positive, repeat test and course of antibiotics (enteroseptics) if PVDT is positive again;
• if LVDT is not available, the doctor should apply conservative methods and not repeat the treatment if the effect of the course of antibiotics (enteroseptics) lasted for at least several months.

When SIBO is detected, the doctor is faced with the question of treatment tactics. The treatment regimen should include antibiotic therapy (ABT) and then, if necessary, pro- and prebiotics in order to restore the microbiotic landscape. Also, the treatment regimen should include measures or drugs to eliminate the underlying cause of the disease or its symptoms. Strict adherence to the diet may lead to improvement in symptoms in patients with celiac disease, which is often associated with SIBO. Surgical correction of bowel disease may be necessary in patients with SIBO that develops against the background of colonic diverticulosis, intestinal fistulas, or strictures. Patients with gastroparesis or dysmotility of the intestine, the main cause of SIBO, should be given prokinetics (eg, itopride hydrochloride). Nutritional support, especially in patients with weight loss or vitamin and mineral deficiencies, is also an important component of the treatment of SIBO. Complexes containing vitamin B12 and fat-soluble vitamins, calcium and magnesium are key components of the treatment.

The mainstay of treatment for SIBO is ABT. Some foreign authors advocate empirical treatment of patients suspected of having SIBO without diagnostic testing. However, this approach is problematic due to the frequent placebo effect, the high cost of antibiotics, potential complications (eg, drug interactions, side effects), and the need to typically repeat antibiotic therapy. A study by M. di Stefano et al. showed that the average duration of clinical improvement with empirical treatment is only 22 days, and this treatment tactic leads to the need for at least 12 seven-day courses of antibiotic therapy per year to alleviate the condition of patients with SIBO and constipation.

Most of the antibacterial drugs (ABPs) currently used to treat SIBO have a weak evidence base. Ideally, antibiotics should be given based on culture and susceptibility testing, but this approach is not acceptable in clinical practice due to its complexity.

Many authors recommend the appointment of broad-spectrum antibiotics effective against anaerobic bacteria: rifaximin (400–600 mg 2 times a day), ampicillin (orally 0.5 g 4 times a day), metronidazole (orally 500 mg 3 times a day ), ciprofloxacin (500 mg 2 r./day), norfloxacin (800 mg/day), vancomycin (125 mg 4 r./day). Sometimes repeated courses lasting from 7 to 14 days are required.

The experience of using probiotics in the complex treatment of SIBO deserves special attention. Probably, the first scientist who published works on probiotics at the beginning of the 20th century was our compatriot, Nobel Prize winner I.I. Mechnikov. He described centenarians in Eastern Europe who drank bulgarian-fermented milk and suggested that proteolytic microbes in the colon produce toxic substances responsible for the aging process, and that consumption of fermented milk products lowers the pH of the colon, inhibiting the growth of proteolytic bacteria, and thus leads to a slowdown in the aging process. Researchers and clinicians around the world are studying and using probiotics for various diseases. In the last 10 years, more than 5,000 articles have been published on the use of probiotic preparations.

L. Richard and R. Parker in 1977 used the term "probiotic" to refer to living microorganisms and their fermentation products that have antagonistic activity against pathogenic microflora. According to the WHO/FAO definition, probiotics are live microorganisms, applied in adequate amounts, that have a healing effect on the human body. Probiotics are also defined as preparations based on intestinal commensals that are able to exercise biological control in the body and have regulatory and trigger properties.

Potential effects of probiotics:

• modulation of intestinal immunity, alteration of inflammatory cytokine profiles and reduction of pro-inflammatory cascades or activation of regulatory strain-specific mechanisms;
• inhibition of pathogenic gas-producing and deconjugating bile salt bacteria, reducing their adhesion;
• changing the bacterial flora by acidifying the colon by fermenting the nutrient substrate;
• increased epithelial barrier function;
• induction of μ-opioid and cannabinoid receptors in intestinal epithelial cells;
• reduction of visceral hypersensitivity, spinal afferentation and response to stress.

Modern probiotics must meet the following criteria:

• contain microorganisms whose probiotic effect has been proven in randomized controlled trials;
• have stable clinical efficacy;
• be phenotypically and genotypically classified;
• stay alive;
• be non-pathogenic and non-toxic, do not cause side effects with prolonged use;
• have a positive effect on the host organism (for example, increase resistance to infections);
• have colonization potential, i.e. remain in the digestive tract until the maximum positive effect is achieved (to be resistant to high acidity, organic and bile acids, antimicrobial toxins and enzymes produced by pathogenic microflora);
• be acid-resistant or enclosed in an acid-resistant capsule;
• be stable and maintain viable bacteria during long shelf life.

Fundamental requirements are also imposed on bacterial strains, on the basis of which probiotics are created. They must:

• be isolated from healthy people and identified to the species according to pheno- and genotypic characteristics;
• have a genetic passport;
• have a wide range of antagonistic activity against pathogenic and opportunistic microorganisms;
• should not inhibit normal microbiocenosis;
• be safe for humans (including immunological safety);
• production strains must be stable in terms of biological activity and meet technological requirements.

All of the above requirements are met by Linex®. It includes Lactobacillus (L.) acidophilus, Bifidobacterium (B.) infantis, Enterococcus (E.) faecium, the content of which is at least 107 microbial bodies. The microorganisms that make up the drug are enclosed in a capsule that opens in the stomach. However, due to the high acid resistance of all components of the drug, bacteria are not destroyed in the stomach, and the drug is able to have a probiotic effect at all levels of the gastrointestinal tract. The combination of lacto- and bifidobacteria with proven probiotic properties in the preparation provides a symbiotic effect in the colonization of the colon, and the presence of an aerobic microorganism - enterococcus contributes to the active immunomodulatory and bactericidal action of the drug at the level of the stomach and small intestine. The microbes that make up Linex® are resistant to most antibiotics, which makes it possible to use the drug against the background of ABT. The resistance of the obtained strains is maintained during repeated inoculation for 30 generations and in vivo. Studies of the drug Linex® showed that the transfer of resistance to other microorganisms does not occur. If necessary, Linex® can be used simultaneously with antibiotics and chemotherapeutic agents. The effectiveness of the components of the drug Linex®, their combinations and the drug itself has been proven in clinical studies for various diseases of the gastrointestinal tract.

The advantage of Linex® is its high safety. With its wide long-term use, side effects have not been registered. Linex® does not have a teratogenic effect. Its safety and good tolerability make it possible to use the drug in patients at risk: pregnant and breastfeeding women, children, including newborns, the elderly, etc. The quality of Linex® is also guaranteed by its production technology that meets all the requirements for the production of probiotics.

At the Department of Microbiology of the Kemerovo State Medical Academy, a study was made of the contents of Linex® capsules.

Microscopic examination of a Gram smear from a suspension of the contents of the capsule revealed the presence of 3 morphotypes of gram-positive bacteria: the correct spherical shape of diplococci, thick pleomorphic rods with swellings at the ends, having the form of a "slingshot", as well as thin single rods with rounded ends. No foreign bacteria were found in the preparation.

On MRS medium, lactobacilli formed medium-sized (2–4 mm) slightly convex grayish moist colonies. Gram smears show thin Gram-positive rods with rounded ends, arranged in random clusters. The quantitative content of L. acidophilus in 1 dose of the drug is 2x107 CFU/ml. The acid-forming ability of lactobacilli reached 102.4°T. Lactobacilli were characterized by medium adhesive activity, since the adhesiveness index (IAM) was 2.71. L. acidophilus was resistant to the following antibiotics: amikacin, gentamicin, neomycin, ceftriaxone, ceftazidime, amoxicillin. Intermediate resistance was found to ciprofloxacin, roxithromycin. The sensitivity of L. acidophilus to imipenem, meropenem, ofloxacin, sparfloxacin has been established.

On bifidum medium, bifidobacteria formed medium (2 mm) and large (5 mm) convex opaque wet colonies. Gram smears show thick, short and long, slightly curved Gram-positive rods with thickened ends. The quantitative content of B. infantis in 1 dose of the drug is 1.5x107 CFU/ml. Acidification - 98.94°T. Bifidobacteria showed the highest adhesive ability among all members of the consortium under study, although the indicators fit into the average values, since the IAM was 2.83. B. infantis was resistant to the following antibiotics: imipinem, meropenem, amikacin, gentamicin, neomycin, ceftriaxone, ciprofloxacin, ceftazidime, amoxicillin. The culture was sensitive to ofloxacin, sparfloxacin, roxithromycin.

On enterococcus agar, E. faecium formed medium-sized (3 mm) pinkish flat tetrazolium-negative colonies. On blood meat-peptone agar, the absence of a hemolysis zone around the colonies was observed. Gram smears show large, spherical Gram-positive bacteria arranged in short chains. The quantitative content of E. faecium in 1 dose of the drug is 2x106 CFU/ml. The acid-forming activity corresponded to 48.5°T. The adhesive activity of enterococci was lower than that of other studied probiotic strains, the IAM was 2.63, which corresponds to the average values ​​of the trait. E. faecium was resistant to the following antibiotics: imipinem, meropenem, amikacin, amoxicillin, ceftazidime, ceftriaxone. Intermediate resistance was observed in relation to roxithromycin, neomycin, gentamicin. Sensitivity to ciprofloxacin, sparfloxacin, ofloxacin and chloramphenicol has been established.

Thus, Linex® is characterized by the following microbiological features: the content of bacteria in 1 dose of the drug was at least 107 CFU/g, the consortium includes L. acidophilus, B. infantis, E. faecium. The total activity of acid formation is 249.84°T. The adhesive activity of all strains in the consortium is from 2.63 to 2.83. All strains of the consortium were resistant to antibiotics of the β-lactam group (amoxicillin, ceftriaxone, ceftazidime) and aminoglycosides (gentamicin, amikacin), which makes it possible to prescribe Linex® while taking the appropriate antibiotics.

It is very important to remember that the recurrence rate of SIBO remains high even after successful treatment. E.C. Lauritano et al. revealed relapses of SIBO in 44% (35/80) of patients after 9 months. after successful treatment with rifaximin. In addition to having an underlying disease leading to SIBO, the authors identified other risk factors for SIBO recurrence: older age (odds ratio (OR) 1.1), previous appendectomy (OR 5.9), and long-term PPI treatment (OR 3.5).

Conclusion

SIBO is defined as an increase in the number and/or change in bacterial species in the upper GI tract. The etiology of SIBO is usually associated with impaired antibacterial defense mechanisms (eg, achlorhydria, exocrine pancreatic insufficiency, immunodeficiency syndromes), anatomical abnormalities (eg, minor intestinal obstruction, diverticula, fistulas, and surgical correction of the blind loop, resection of the iliac-blind intestines) and/or dysmotility.

SIBO is often misdiagnosed and, in general, is not an independent disease. Clinical symptoms may be non-specific (dyspepsia, bloating, abdominal discomfort). However, SIBO can cause severe disorders such as maldigestion and malnutrition. For the diagnosis of SIBO, non-invasive LVDT is most often used. Therapy for SIBO should be comprehensive and include treatment of the underlying disease, normal nutrition and course sanitation of the intestines with the use of antibiotics, and then restoration of the microflora with the help of pre- and probiotics. The probiotic of choice may be Linex®, which is highly effective in the treatment of intestinal diseases, including SIBO. The recommended duration of admission is at least 2 weeks. The prognosis of SIBO is usually serious and is determined by the course of the underlying disease that led to its formation.

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Inevitably, EPI is accompanied by impaired digestion and absorption of nutrients, which can lead to the development of malabsorption. It is believed that adequate therapy with enzyme preparations should compensate for the deficiency of endogenous enzymes and restore normal digestion. However, in practice, it is far from always possible to easily cope with EPI. The main reason for this, as a rule, is associated with an insufficient dose of enzyme agents or the choice of an ineffective drug. There is a second, very serious reason for the persistent course of EPI and the low, at first glance, the effectiveness of enzyme therapy. This is associated with the development of small bowel bacterial overgrowth syndrome (SIBO), known in the English literature as "bacterial overgrowth". SIBO is little known to a wide range of doctors and is not taken into account in treatment tactics. Therefore, the purpose of this article was to familiarize internists and gastroenterologists with modern approaches to the correction of SIBO in CP. Normal microflora of the gastrointestinal tract

From modern positions, the normal human microflora (normoflora, microbiota) is considered as a set of many microbiocenoses occupying numerous ecological niches (biotopes) on the skin and mucous membranes of all body cavities open to the external environment. The total number of bacteria in an adult is 1015 cells, which is more than 10 times higher than the number of own cells of the macroorganism. The currently existing regulatory document "Russian industry standard for dysbacteriosis" offers the following definition of normal flora: it is "a qualitative and quantitative ratio of various microbial populations of individual organs and systems that maintain the biochemical, metabolic and immunological balance of the macroorganism necessary to maintain human health." From this definition it follows that the normoflora of each biotope performs numerous functions not only to maintain its functioning, but also the homeostasis of the body as a whole.

The species and quantitative composition of the microflora of each biotope of the gastrointestinal tract (GIT) is quite constant due to the influence of numerous protective factors both from the host organism and the microbiota itself:

genetic predisposition

Acidic gastric environment

Normal motor-evacuation function of the gastrointestinal tract

Anatomical sphincters of the gastrointestinal tract

Constant level of intraluminal pH in different biotopes

The state of the immune system of the mucous membranes

Bactericidal substances produced by mucous membranes (lysozyme, lactoferrin, etc.)

Phagocytic activity of mucosal macrophages

Secretory IgA

Bacterial colicins and microcins (endogenous peptide antibiotics of microbial origin)

Only in the human gastrointestinal tract there are more than 400 species of bacteria - representatives of 17 different families. The human digestive tract is inhabited by bacteria unevenly.

As can be seen from the table, the highest density of microbial contamination in the colon is about 400 different species. The total biomass of colonic microbial cells is approximately 1.5 kg, which corresponds to 1011–1012 CFU/g of content and is about 1/3 of the dry weight of feces. It is the large intestine, due to such a high contamination, that bears the greatest functional load compared to other biotopes. The content of bacteria in the upper intestine varies in a narrow range of 103–104 CFU/ml of intestinal contents.

Bacteroids, eubacteria, bifidobacteria, peptostreptococci, ruminococci, clostridia, and lactobacilli are the main mass of bacteria in the large and lower sections of the small intestine, and bacteroids, lactobacilli, and cocci in the upper sections of the small intestine (Table 1). Despite the relatively small number of microorganisms in the proximal small intestine, their functions are very important for the life of this biotope, in particular, for maintaining the luminal pH and the immune status of the mucosa. The normal microflora of the gastrointestinal tract as a whole performs metabolic, protective, antimutagenic and anticarcinogenic functions. Metabolic and anticarcinogenic functions fall mainly on the flora of the colon, and the microflora of all biotopes participates in the implementation of antitoxic, protective and immune functions, in maintaining colonization resistance and microbial antagonism in relation to pathogens and opportunistic pathogens. This applies equally to the upper sections of the small intestine. Colonization resistance is understood as a set of mechanisms that ensure the constancy of the species and quantitative composition of microbial populations in a particular biotope, preventing the reproduction of opportunistic and pathogenic flora and its translocation into uncharacteristic biotopes and into the internal environment of the body. A manifestation of such a translocation of the microflora can be SIBO in the small intestine with an increase in the microbial contamination of the latter by more than 104 CFU/ml of intestinal contents.

Syndrome of excessive bacterial growth (syndrome of excessive contamination - bacterial overgrowth)

As mentioned above, the normal content of bacteria in the upper intestines fluctuates in a narrow range of 103-104 CFU / ml of intestinal contents, and this value is a kind of constant for the small intestine. The species composition of the microbiota is also quite constant: bacteroids, lactobacilli, cocci.

Summarizing the existing definitions, from our point of view, we can give the following definition of SIBO syndrome: bacterial overgrowth syndrome is a seeding of the proximal parts of the small intestine over 104 m.k. (CFU) / ml of intestinal contents due to opportunistic microflora coming from the upper gastrointestinal tract (or upper respiratory tract) or due to retrograde translocation of opportunistic representatives of the colon microbiota.

It should be emphasized that the concept of SIBO in the international literature refers to the overgrowth of flora only in the small intestine, but not in the large intestine.

There are several main mechanisms leading to SIBO. The first mechanism is due to hypo- or achlorhydria of any origin. A decrease in the protective acid barrier allows microbes from the oral cavity and upper respiratory tract to colonize the stomach and then the small intestine. This process may be based on various reasons, but most often this pathway of microbial contamination of the small intestine occurs after gastric resection or gastrectomy, with long-term use of gastric secretion inhibitors, with autoimmune gastritis, with autoimmune diseases such as pernicious anemia and scleroderma.

The second mechanism for the development of SIBO is due to a violation of the so-called "intestinal clearance", i.e. a violation of the ability of the small intestine to eliminate pathogens or opportunistic microorganisms that have fallen into it. Impaired clearance occurs with a decrease in the activity of protective mechanisms that maintain the constancy of the microbiota of the small intestine: inhibition of motor activity, a decrease in the synthesis of bactericidal substances and secretory IgA, a decrease in the phagocytic function of macrophages of the small intestine mucosa, etc.

The third mechanism is associated with retrograde translocation of microflora from the large intestine to the small intestine due to insufficiency of the ileocecal valve during inflammation or motor disorders of the large intestine. Almost any gastroenterological disease can lead to the development of SIBO.

Methods for assessing SIBO

Diagnosis of SIBO is very difficult, because methods of sampling the contents of the small intestine are too laborious. For this purpose, a simple and convenient method has been developed to determine the concentration of hydrogen in the exhaled air after a carbohydrate load with glucose or lactose (hydrogen breath test). In the presence of SIBO, the level of hydrogen in the exhaled air is high due to the formation of microbial metabolites in the small intestine. The same method can be used to monitor the results of treatment with various drugs that inhibit the growth of excess flora in the small intestine. The method is cheap, easy to perform, however, unfortunately, it is not widely used in Russia.

Chronic pancreatitis and SIBO

According to J.E. Dominguez-Munoz, SIBO occurs in 40% of patients with CP and is one of the most common causes leading to insufficient effectiveness of enzyme replacement therapy.

Thus, HP is accompanied by:

Violation of the processes of digestion and absorption

Development of bacterial overgrowth in the small intestine

Violation of the motor function of the gastrointestinal tract

The initial violation of cavitary digestion in CP through the interaction of complex mechanisms is aggravated by a violation of membrane digestion, and all participating mechanisms operate on the principle of a vicious circle.

Treatment of bacterial overgrowth syndrome

It should be borne in mind that SIBO is not an independent pathology, but only a secondary syndrome that accompanies many pathological conditions. If, as a rule, there are no clearly defined clinical symptoms in violations of the colon microbiota, then with SIBO, flatulence, stool disorders, and sometimes severe diarrhea usually occur. At the same time, all of these symptoms are not specific, and it is not possible to associate them unambiguously with SIBO. In the context of this article, flatulence, diarrhea, stetorrhea can equally be a consequence of both EPI and SIBO.

In any case, microbial disorders in both the large and small intestine are always secondary, therefore, in order to correct them, it is necessary first of all to eliminate the negative factors causing them (for example, medicinal or environmental influences) or to treat the underlying disease. It is important to emphasize that the correction of SIBO is not an end in itself and is carried out:

If it is impossible to eliminate its cause

Under the action of a permanent aggressive factor (for example, chemotherapy)

As an additional measure, with insufficient effectiveness of the treatment of the underlying disease that caused these disorders.

An ideal illustration of these provisions is SIBO developing against the background of EPI. Ideally, when an adequate dose of enzyme preparations is prescribed, digestion is restored and additional correction of SIBO is not required. However, SIBO is one of the most common reasons leading to insufficient effectiveness of enzyme replacement therapy. In one of the studies, the effect of Creon therapy on SIBO (according to the hydrogen breath test) was evaluated in 15 patients with EPI in CP. These patients within 2 months. conducted therapy with Creon 100-150 thousand IU per day. In the majority (65% - 10 patients), according to the repeated hydrogen test, SIBO was eliminated, in 53% (8 patients) flatulence disappeared, in 73% (11 patients) there was an improvement in well-being, but dyspeptic symptoms persisted.

Based on the foregoing, the administration of adequate doses of effective enzyme agents (Creon 25,000–40,000 IU with each meal) should be the first line therapy for pancreatic diseases with EPI with or without SIBO. With its insufficient effectiveness, the appointment of drugs to eliminate microbial growth in the small intestine is indicated. Therapeutic tactics for microbial disorders depends on the degree of their severity, the presence of clinical manifestations, and the translocation of bacteria to other biotopes. In some cases, in the presence of SIBO, it becomes necessary to conduct "selective microbial decontamination of the intestine." This concept implies carrying out intestinal sanitation (decontamination) with drugs that selectively suppress the growth of foreign flora and do not affect the normoflora. For the purpose of decontamination, several groups of agents are used:

Antibacterial drugs

Non-pathogenic fungi

Spore-forming preparations based on representatives of transient flora

microbial metabolites.

Antibiotics

The optimal antibacterial drug for decontamination of the small intestine and elimination of SIBO should meet the following requirements:

Have minimal absorption from the gut

Create a high concentration in the intestinal cavity

Possess selectivity (should suppress foreign flora and not affect the normoflora

Have a broad spectrum of antimicrobial activity, including aerobes and anaerobes

Have a minimum of side effects and be safe

Have proven clinical efficacy

One of the newest in Russia and the most interesting drug from all three points of view is a derivative of rifamycin - the drug rifaximin (Alfa-normix). It is not absorbable<1%) при приеме внутрь антибиотик, достигающий высоких концентраций в слизистой оболочке ЖКТ.

The drug does not act outside the gastrointestinal tract, i.e. is a locally acting intestinal antiseptic. Rifaximin is well tolerated, has a minimum of side effects and does not cause bacterial resistance. The drug has a wide spectrum of antibacterial action against gram-positive (Enterococcus spp, M. tuberculosis, Streptococcus pyogenes, Streptococcus faecalis, Streptococcus pneumoniae, Staphylococcus epidermidis, Staphylococcus aureus) and gram-negative (Escherichia coli, Shigella spp, Salmonella spp, Yersinia enterocolica, Proteus spp, Vibrio cholerae) aerobic bacteria and Gram-positive (Clostridium perfrigens, Clostridium difficile, Peptococcus spp, Peptostreptococcus spp) and Gram-negative (Bacteroides spp, Bacteroides fragilis, Helicobacter pylori) anaerobes. This spectrum of action determines the therapeutic potential of the drug. Thus, rifaximin satisfies all the basic requirements for an ideal antibacterial drug. It has been successfully used in acute intestinal infections, for the sanitation of the colon with "dysbacteriosis", for the correction of SIBO, with antibiotic-associated intestinal lesions and with hepatic encephalopathy. For SIBO proven by the hydrogen breath test, rifaximin is used 400 mg 3 times a day for 7 days. At the same time, the level of exhaled hydrogen decreases by 3–5 times already by the third day of treatment, which indicates a rapid sanitation of the small intestine.

For a long time, various antibiotics (tetracyclines, lincomycin, ampicillin, etc.) have been used to treat SIBO in various pathologies, which do not have selectivity, do not affect the anaerobic flora, are rapidly absorbed from the gastrointestinal tract and have a wide range of side effects (including antibiotics). associated diarrhea) and suppress normal flora. To demonstrate the effectiveness of rifaximin, a double-blind study was conducted confirming the priority of rifaximin over tetracycline in SIBO. In this study, SIBO in two groups of patients was assessed by a hydrogen breath test and the peak of hydrogen excretion in exhaled air and the total hydrogen concentration after a glucose load before and 3 days after the end of the antibiotic course were determined. It was shown that at equal initial levels of hydrogen, its peak after glucose loading, as well as the total concentration in exhaled air after treatment, was significantly lower in patients treated with rifaximin compared with the group treated with chlortetracycline.

Other effective antibacterial agents include oxyquinolone derivatives, low-absorbable nitrofuran derivatives (nifuroxazide) and nitroimidazoles (metronidazole, tinidazole). Although the last group is absorbed from the large intestine, nevertheless, its use is effective, mainly in case of contamination with anaerobic microorganisms. The duration of the decontamination course for SIBO is 12–14 days.

Non-pathogenic fungi

In case of intolerance to antibacterial drugs, it is possible and effective to prescribe drugs based on non-pathogenic yeast fungi of the genus S. boulardii. At the same time, S. boulardii does not inhibit the growth of obligate microorganisms in the intestinal cavity and is resistant to the action of hydrochloric acid. With daily intake, they are found in all parts of the gastrointestinal tract, including the small intestine. These yeasts are a transient flora for humans, therefore, 2–5 days after the end of the drug intake, they are completely eliminated from the body without side effects. The drug is not absorbed from the lumen of the gastrointestinal tract and is a locally acting intestinal antiseptic. The antimicrobial activity of S. boulardii was established in vitro and in vivo against pathogens of intestinal infections (Cl. difficile, Salmonella, Shigella, Yersinnia), protozoa (Giardia and a number of) opportunistic microorganisms (pathogenic cocci, fungi, Klebsiela, etc.) that can lead to the development of SIBO.

Spore-forming non-pathogenic antibacterial agents can also be used in SIBO as an alternative to antibiotics in case of intolerance. This group includes drugs based on the hay bacillus Bacillus subtilis and a similar microorganism B. cereus. Spore microorganisms are a transient flora for humans, therefore, they are quickly eliminated from the intestine after stopping the intake. The mechanism of action of these drugs is due to the formation of acid metabolites in the process of life and a decrease in pH throughout the intestine, thereby inhibiting the growth of opportunistic flora. In addition, these drugs synthesize a number of digestive enzymes, partially compensating for the decrease in the intestine's own enzyme activity when damaged by bacteria and their toxins. The course of treatment for SIBO is 10–14 days. A longer course is undesirable, because. B. cereus are capable of producing enterotoxins that cause diarrhea.

Microbial metabolites

An additional agent that restores the microflora of the predominantly small intestine is the microbial metabolite hilak forte. The main biologically active components that make up hilak forte are short-chain fatty acids (SCFA) and lactic acid, obtained from saccharolytic and proteolytic representatives of the normal intestinal microflora. The concentration of biologically active substances in one drop of the drug corresponds to the action of the corresponding metabolites from 1010 bacteria. The mechanism of action of hilak forte on the normalization of the composition and functions of the microbiota and on the restoration of intestinal activity is mediated by its constituent components. SCFA contained in the preparation provide mucous membranes with additional energy, promote the regeneration of damaged epithelial cells of the intestinal wall, and improve mucosal trophism. The influence of acid metabolites (SCFA, lactic acid) ensures the regulation of intraluminal pH, which leads to inhibition of the growth of pathogens and opportunistic pathogens throughout the intestine.

Thus, the tactics of treating CP with SIBO should be built as follows:

Adequate enzyme therapy (Creon 75,000 IU or more per day)

Decontamination of the small intestine: antibiotic therapy (rifaximin)

Microbial metabolites

Normalization of colonic microbiocenosis with pro- and prebiotics (if necessary)

Elimination of motor disorders - duodenal hypertension, accelerated propulsion (if necessary).

The human gastrointestinal tract (GIT) is normally inhabited by 300 to 500 different types of bacteria. The microbial landscape of the proximal and distal small intestine differs significantly. So, if in the upper parts of the small intestine the number of microorganisms is approximately 10 2 colony-forming units / ml (CFU / ml), then closer to the large intestine there are already 10 9 CFU / ml. In addition, Gram-positive aerobic bacterial species are most common in the proximal small intestine, while Gram-negative anaerobic bacteria are more common in the distal intestine. In healthy individuals, the normal intestinal microflora is maintained by the following main physiological mechanisms: pH level in the stomach, pancreatic secretory activity and choleresis, small intestinal motility, and structural integrity of the gastrointestinal tract. Disruption of any of these defense mechanisms can lead to the development of small intestinal bacterial overgrowth syndrome (SIBO).

The most important etiological factors for SIBO include the following:

• dysfunction of the ileocecal valve (inflammatory and tumor processes, primary functional failure);
• consequences of surgical operations (anatomical or surgically formed blind loop; small-colonic anastomosis or fistula, vagotomy, cholecystectomy, resection of the small intestine);
• diseases of the gastrointestinal tract associated with motor disorders - gastrostasis, duodenostasis, stasis of the contents in the small and large intestines (chronic constipation, including in diabetic patients);
• disorders of cavity digestion and absorption (maldigestion and malabsorption), including those associated with achlorhydria of various origins (operated stomach, chronic atrophic gastritis, long-term use of proton pump inhibitors), with exocrine pancreatic insufficiency (chronic pancreatitis), with pathology of the biliary tract (cholelithiasis disease, chronic cholecystitis);
• enteropathy (disaccharidase deficiency and other food intolerances);
• prolonged nutritional imbalance;
• chronic inflammatory bowel disease, diverticulitis, short bowel syndrome;
• intake of bacteria from an extraintestinal reservoir (for example, with cholangitis);
• local and systemic immune disorders - radiation, chemical effects (cytostatics), AIDS;
• antibiotic therapy;
• stresses of various origins;
• tumors of the intestine and mesenteric lymph nodes.

In addition, various diets for weight loss and “cleansing” with the use of volumetric enemas have a negative impact on the intestinal microbial landscape, especially colon hydrotherapy, which has a certain popularity, but is strongly discouraged by gastroenterologists around the world, as it grossly violates microbial biotopes.

With SIBO, not only the number of microorganisms increases, but the spectrum of microflora also changes - it shifts towards gram-negative bacteria and anaerobes. In 30% of healthy people, the jejunum is normally almost sterile, in the rest it has a low density of bacterial colonization, which increases as it approaches the colon, and only in the distal ileum is the fecal microflora found: enterobacteria, streptococci, anaerobes of the genus bacteroids, etc. . .

The symptoms of SIBO (flatulence, bloating, abdominal pain or discomfort, diarrhea, fatigue, weakness, weight loss) are not characterized by specificity, they reflect the prevalence of inflammation of the intestinal mucosa, “layer” on the manifestations of the underlying disease, which is the cause of the development of SIBO. More severe symptoms, including malabsorption, nutrient deficiencies, and bone metabolism disorder, point to complications of SIBO. The nonspecificity of these symptoms is often the cause of diagnostic errors and requires a differential diagnosis with irritable bowel syndrome, lactose intolerance, or fructose intolerance.

To characterize SIBO, it is necessary not only to determine the absolute number of bacteria, but also their species typing, which determines the manifestation of signs and symptoms of the disease. If overgrowth of bacteria that metabolize bile salts into unconjugated or insoluble compounds predominates, then the clinical picture of fat malabsorption or diarrhea caused by bile acids develops. Deconjugated bile acids can have a toxic damaging effect on enterocytes, which disrupts not only the assimilation of fats, but also carbohydrates and proteins. With an overgrowth of bacteria that preferentially metabolize carbohydrates into short-chain fatty acids and gas, the clinical picture is dominated by bloating without diarrhea, because the resulting metabolic products can be absorbed.

Verification of excessive bacterial growth in the small intestine is carried out using direct and indirect methods for diagnosing this syndrome. The “gold standard” for diagnosing SIBO is culture of microflora; this requires aspiration of the contents of the small intestine with immediate inoculation of the aspirate on a nutrient medium. However, bacterial overgrowth can affect the most distal portions of the small intestine that are out of reach of the instrumentation.

Fecal culture, which is used in our country as a method for assessing the microbial biocenosis of the intestine, is not very informative in the case of SIBO, since even with the maximum approximation to the rules for conducting microbiological studies, it can give an idea of ​​the microbial composition of only 12-15 typified species of bacteria of the distal colon. In addition, if we take into account that the main normal flora of the intestine is anaerobes, and the patient collects and carries his feces to the bacteriological laboratory in the presence of ordinary air, which includes oxygen, then most of these bacteria die, but the pathogenic aerobic flora multiplies very quickly. What will grow when sowing such content? One can only guess, but this seeding is unlikely to be relevant even to the microbial landscape of the rectum. Fecal examinations are informative for the search for infectious pathogens or helminthic invasion, but not for the diagnosis of SIBO.

In addition to seeding the microflora of the small intestine, other methods are applicable to establish excessive bacterial growth, based on the study of the concentration of indican produced by indole-positive microorganisms, phenol and paracresol, which are metabolites of aerobic (to a lesser extent) and anaerobic (to a greater extent) microorganisms, as well as a method for diagnosing the state of microbiocenosis of various biotopes, including the intestine, based on the determination of short-chain (monocarboxylic) fatty acids (SCFA), which are metabolites of mainly anaerobic genera of microorganisms, by gas-liquid chromatographic analysis.

Indirect methods for diagnosing SIBO include tests based on the study of microflora metabolites. These are 14C- or 13C-glycocholate, 14C-D- or 13C-D-xylose breath tests, which require isotopes and a specialized laboratory, as well as hydrogen breath tests with lactulose, glucose, lactose and other sugars.

An alternative method is hydrogen breath tests, which are most commonly used to diagnose SIBO. These are simple, informative and non-invasive methods that were developed about 25 years ago to diagnose various diseases of the alimentary canal, primarily to determine carbohydrate malabsorption and bacterial overgrowth in the small intestine. Currently, this diagnostic method is being rapidly introduced into clinical practice all over the world. Some methodological aspects of individual hydrogen tests are still not standardized, so the study of the effectiveness of existing and the development and/or improvement of new tests continues worldwide.

In 2008, the Rome Consensus on Hydrogen Tests was adopted, which sets out the recommendations of international experts for clinical practice regarding the indications and methods for performing hydrogen breath tests in diseases of the alimentary canal. The method is cheap, simple, but many practitioners not only do not know the main provisions of the consensus, but are still not familiar with this test at all, do not know its diagnostic capabilities, certain limitations and shortcomings.

The hydrogen content in the lowest layer of the atmosphere - the troposphere - is 0.575 ppm, while its content in the exhaled air of a healthy person is 20-30 ppm. and more (with the exception of some people whose intestinal microflora produces more methane than hydrogen, a small part of the population produces gases that have not yet been determined, being non-responders for hydrogen tests). An increase in hydrogen release occurs when part of the absorbed carbohydrates and proteins is not absorbed or digested by the mucous membrane of the small intestine and is used by the bacterial colonies of the large intestine for fermentation with the release of hydrogen. Some of this hydrogen is absorbed by the intestinal mucosa into the bloodstream and transported to the lungs, where it is released with exhaled air. Thus, in case of malabsorption or bacterial overgrowth in the small intestine, absorbed carbohydrates (glucose, fructose, lactulose, galactose, xylose, lactose, etc.) or substances similar to carbohydrates in molecular structure (sorbitol, xylitol, mannitol, etc.) d.), cause an increase in the concentration of hydrogen in the exhaled air. If gases are not utilized by bacteria, they are absorbed and then excreted with respiration or during bowel movements. In particular, hydrogen can be rapidly absorbed into the blood and excreted by the lungs, which is the rationale for the hydrogen breath test, which is widely used to detect carbohydrate malabsorption. Absorbed H 2 is almost completely removed from the blood in one passage through the lungs, so the level of hydrogen excretion should be equivalent to its absorption in the intestine. About 14-20% of H 2 released in the colon is excreted through the lungs. Thus, the concentration of hydrogen in exhaled air can be a measure of its intestinal production.

The hydrogen test is used for an approximate idea of ​​the degree of bacterial contamination of the small intestine. This indicator is directly dependent on the concentration of hydrogen in the exhaled air on an empty stomach. In patients with intestinal diseases that occur with chronic recurrent diarrhea and bacterial contamination of the small intestine, the concentration of hydrogen in the exhaled air significantly exceeds 15 ppm. In case of bacterial contamination of the small intestine, the "peak" of the increase in hydrogen concentration in the exhaled air appears much earlier. This test has the following advantages:

• unlimited access to bacteria from all parts of the digestive tract (unlike glucose, which allows you to evaluate excess growth only in the proximal parts of the small intestine);
• good correlation between the rate of hydrogen production in the digestive tract and the rate of hydrogen release in the lungs;
• a clear distinction between the metabolic activity of bacteria and their host.

With the help of hydrogen breath tests, a wide range of disorders of the gastrointestinal tract can be diagnosed:

• an increase in the transit time of carbohydrates through the gastrointestinal tract;
• bacterial overgrowth syndrome;
• malabsorption or maldegestia of certain carbohydrates;
• intolerance to lactulose, sucrose, lactose.

Lactulose is an artificial synthetic disaccharide composed of fructose and galactose. In the human body, there is no enzyme capable of decomposing it into monosaccharides. The concentration of hydrogen in the exhaled air during a hydrogen breath test with lactulose can correspond to different types of graphs:

• normal - lactulose does not decompose in the small intestine, when it reaches the large intestine, it undergoes fermentation with the release of hydrogen, which is absorbed into the blood and excreted with exhaled air;
• pathological - with excessive bacterial growth, lactulose is fermented already in the small intestine, the hydrogen concentration reaches a maximum earlier.

The lactulose test is the most common non-invasive test for determining the intestinal transit time of various carbohydrates. After the basic exhalation, the subjects are asked to drink a solution of lactulose in a small (50-150 ml) amount of water: children under 6 months - 3.34 g (5 ml), children over 6 months - 6.68 g (10 ml), adults - 10 g (15 ml). The measurements are recorded directly by a trained nurse, the conclusion is given by a gastroenterologist, the clinical evaluation and treatment is carried out by the doctor who referred the patient for examination. An increase in the concentration of hydrogen over 15 ppm is considered diagnostic. An early peak in the concentration of H 2 indicates a syndrome of excessive bacterial growth, a delay in the growth of the concentration of H 2 indicates a prolongation of the intestinal transit time. The test is carried out for 2.5-4 hours, the patient exhales into the tube of the device or a special, hermetically sealed bag of a certain volume, every 15-30 minutes, depending on the phase of the study. For the accuracy of the test, it is necessary that the production of hydrogen from the unabsorbed carbohydrate of the test food by the bacteria in the colon should lead to a clearly distinguishable increase in the hydrogen signal in the exhaled air. Based on the results of the studies, it is advisable to refrain from eating on the night before the examination. In addition, smoking can change the release of hydrogen with exhaled air, so patients are not allowed to smoke before and during the test.

We have five years of experience with hydrogen breath tests using the Gastrolyzer 2 in practice. This article provides some interesting clinical examples from our practice. In addition to respiratory hydrogen tests with lactulose, all patients were prescribed standard examinations: in addition to general clinical methods, a set of methods for detecting celiac disease, fecal examination for Giardia antigen, coprogram, fecal elastase-1, computer colonoscopy or irrigoscopy, fibrocolonoscopy (if indicated), psychological testing, except In addition, each patient completed the Irritable Bowel Syndrom Quality of Life (IBS-QoL) questionnaire, designed to assess the quality of life of patients suffering from irritable bowel syndrome (IBS) .

Patient A., age 60 years. Complaints about constant mushy stools with a frequency of up to 5-6 times a day for two years, recurrent abdominal pain, bloating, flatulence, intolerance to a number of foods, weight loss of 17 kg over two years, deterioration in health in the last 3 months, the need to comply with strict a diet including rice porridge in water, crackers, strong tea, etc. He was examined and treated by an infectious disease specialist with some improvement, which was not long-term. According to the results of standard examinations, iron deficiency anemia of mild severity, a decrease in magnesium and calcium levels in the blood were established. According to the respiratory hydrogen test, severe bacterial contamination of the small intestine was diagnosed (Fig. 1, No. 1). Treatment was prescribed - antibiotics, then a course of prebiotics and probiotics, multivitamins. A month later, at the reception, the patient noted a significant improvement in well-being, weight gain of 5 kg, normalization of the stool. After 6 months, the results of blood tests and a hydrogen breath test showed no pathology (Fig. 2, No. 1).

Patient U., age 72 years. Complaints of nausea, bitterness in the mouth in the morning, alternating constipation and diarrhea, periodic pain in the abdomen on an empty stomach and some time after eating, bloating. Lost 15 kg over the past 3 years, follows a strict diet with the exception of fatty, fried and dairy foods, etc. According to the results of the study, amylorrhea and steatorrhea were detected according to the coprogram, the content of fecal elastase-1 was 50 μg/g feces, severe hypomotor dysfunction gallbladder. The data of the respiratory hydrogen test are normal (Fig. 1, no. 2). A treatment regimen for chronic pancreatitis and biliary insufficiency was prescribed with a good clinical effect over time.

Patient A., age 42 years. Complaints of alternating constipation and diarrhea, nervousness, weakness, increased fatigue. Repeatedly treated for "dysbacteriosis" without effect. Standard studies without pathology. According to the data of the breath test (Fig. 1, No. 3), one can assume a decrease in the rate of transit through the small intestine, a decrease in the level of normal flora in the large intestine. According to psychological testing - somatoform anxiety disorder within the framework of IBS, moderate severity. Treatment with psychotropic drugs, prebiotics and probiotics was prescribed. In the dynamics after 6 months, there was a cessation of complaints and normalization of the respiratory hydrogen test (Fig. 2, No. 3).

Patient R., age 64. The diagnosis was cirrhosis of the liver of viral etiology in the outcome of hepatitis C, class B according to the Child-Pugh classification. Complaints of pronounced flatulence, loose stools, abdominal pain, which are aggravated after taking lactulose, which is part of the treatment regimen. The respiratory hydrogen test showed a pronounced bacterial contamination of the small intestine (Fig. 1, No. 4). In such situations, this test can be used to monitor SIBO in order to prescribe antibiotic therapy. In the dynamics after a course of antibiotic therapy, a significant positive trend was noted, but a second course with the replacement of the drug was recommended (Fig. 2, No. 4).

Patient N., age 32 years. Complaints of constant aching pain in the abdomen, aggravated by stress or after taking certain foods, periodic mushy stools with a frequency of up to 2-4 times a day, bloating, fatigue, nervousness, anhedonia. As a result of standard studies, no pathology was detected. For several years he has been visiting gastroenterologists, surgeons, the prescribed treatment for "dysbacteriosis" is ineffective, and his weight is stable. Based on the results of the breath test, SIBO was detected (Fig. 1, no. 5). Psychological questionnaires revealed severe somatoform depressive disorder within IBS associated with SIBO. Treatment with antibiotics, prebiotics, probiotics, antidepressants was prescribed. After a course of treatment with SIBO, the patient clinically improved (Fig. 2, No. 5), but the pain syndrome was not completely stopped, the patient continues to take antidepressants.

Patient M., age 37 years. Complaints about periodic mushy stools since childhood, poor tolerance to dairy products, for the last three years, mushy stools have become constant with a frequency of 4-8 times a day, she lost 8 kg, body mass index was 17.2 kg/m 2 . Standard examinations revealed celiac disease, iron deficiency anemia of mild severity, according to the hydrogen breath test, SIBO was established (Fig. 1, No. 6). Treatment was prescribed, which included a gluten-free diet, antibiotics, probiotics, prebiotics, multivitamins with a complex of basic microelements. An improvement was noted in the dynamics - an increase in weight of 3 kg, the frequency of mushy stools decreased to 2-3 times a day. The results of the respiratory hydrogen test correspond to the norm (Fig. 2, No. 6).

Today, hydrogen breath tests are considered as informative methods for diagnosing certain physiological and pathological processes, such as malabsorption of carbohydrates (lactose, fructose, sorbitol), SIBO, as well as determining the time of orocecal transit. Due to their non-invasiveness and relative cheapness, in many cases they are diagnostic tests of the first line of examination. The significance of hydrogen breath tests and clinical indications for their implementation in gastroenterological practice are constantly being refined and expanded. Practitioners should be aware of the advantages and disadvantages of these examination methods and apply them widely in the treatment of patients.

It should be noted that the problem of treating excessive bacterial contamination is not as relevant as its diagnosis. Treatment of patients with bacterial overgrowth syndrome consists in eliminating excessive bacterial colonization of the small intestine, restoring intestinal microbiocenosis, and normalizing intestinal digestion. In parallel, symptomatic treatment is carried out, aimed at eliminating or reducing the severity of the main symptoms of the disease.

Many authors recommend the appointment of broad-spectrum antibacterial drugs effective against anaerobic bacteria - rifaximin (400-600 mg orally 2 times a day), tetracycline (0.25 g orally 4 times a day), ampicillin (0. 5 g 4 times a day), metronidazole (orally 500 mg 3 times a day), ciprofloxacin (orally 500 mg 2 times a day), norfloxacin (orally 800 mg per day), vancomycin (orally 125 mg 4 times in a day) . Sometimes repeated courses lasting from 7 to 14 days are required. In our practice, we most often use rifaximin at a dose of 400 mg 2 times a day, often for a significant improvement in well-being and to normalize the respiratory hydrogen test, one course of treatment is enough. If the pain syndrome and intestinal dyspepsia persist with the normalization of the respiratory hydrogen test, then this symptomatology is considered as a manifestation of IBS. When analyzing the data we have accumulated over 5 years, the frequency of association of IBS and SIBO was detected in more than 60% of patients.

After a course of antibiotic therapy, we prescribe probiotics and prebiotics, for example, Linex® (manufactured by Sandoz Pharma, Switzerland), a probiotic preparation that meets modern requirements. Its composition includes L. acidophilus, B. infantis, Ent. faecium, the content of which is at least 107 microbial bodies. The microorganisms that make up the drug are enclosed in a capsule that opens in the stomach. Due to the high acid resistance of all components of the drug, bacteria are not destroyed in the stomach and the drug is able to have a probiotic effect at all levels of the gastrointestinal tract. The microbes that make up Linex® are resistant to most antibiotics, which makes it possible to use the drug against the background of antibiotic therapy. The resistance of the obtained strains is maintained during repeated inoculation for 30 generations and in vivo. Studies of the drug Linex® showed that the transfer of resistance to other microorganisms does not occur. If necessary, Linex® can be used simultaneously with antibacterial and chemotherapeutic agents.

The choice of a probiotic for empirical correction of the intestinal microbial landscape is a rather difficult task, since many drugs are ineffective. Perhaps this is due to the rapid death of the introduced strains due to the high aggressiveness of the immune system in relation to its own microflora. Many problems of correction of intestinal dysbacteriosis can be resolved by developing and introducing fundamentally new drugs - microbial metabolites. The first representative of this group was Hilak® forte (manufactured by Ratiopharm GmbH, Germany). Strictly speaking, these products are neither probiotics nor prebiotics. Nevertheless, they can be conditionally called metabolite probiotics, since they contain the waste products of normal symbionts. The preparation contains a sterile concentrate of metabolic products of saccharolytic ( Lactobacillus acidophilus, Lactobacillus helveticus and Streptococcus faecalis) and proteolytic ( E. coli) representatives of indigenous microflora, SCFA. Additionally, Hilak® forte contains biosynthetic lactic, phosphoric and citric acids, potassium sorbate, a balanced complex of buffer salts (acid sodium and potassium phosphate) and a number of amino acids. The biological activity of 1 ml of Hilak® forte corresponds to the activity of approximately 100 billion living microorganisms.

Against the background of the accelerated development of normal intestinal symbionts, under the action of the drug, the natural synthesis of B and K vitamins is normalized. .

Works have been published on the use of Hilak® forte in practical medicine both in Russia and abroad. As a result of studies of the effectiveness of the drug, it was found that its prebiotic properties are aimed not only at optimizing the functional state of the intestine, but also participate in the regulation of important homeostatic mechanisms at the macroorganism level. In 2003, Hilak® forte was awarded the Platinum Ounce Award by an independent expert committee. This drug realizes its positive effect on the physiological functions of the macroorganism as a result of the modulation of immune responses, changes in the function of macrophages and the production of cytokines, as well as activation of the immune system associated with the mucous membranes. By normalizing the water and electrolyte balance and pH in the intestinal lumen, Hilak® forte is a mild regulator of the motor function of the colon, promotes rapid restoration of intestinal biocenosis through the normalization of normal microflora - bifidobacteria and lactobacilli, stimulates the synthesis of epithelial cells of the intestinal wall of the intestine. Due to the fact that Hilak® forte contains biosynthetic lactic acid and its buffer salts, the drug normalizes acidity in the digestive tract, regardless of the state of the secretory function of the stomach. Lactic acid creates conditions unfavorable for pathogens.

Hilak® forte is indicated for a wide variety of conditions accompanied by microbial imbalance: disorders of maldigestion and malabsorption of various origins, impaired peristaltic activity of the intestine, during the recovery period after acute infectious enterocolitis, etc. The appointment of Hilak® forte is advisable during antibiotic treatment and for some time after their cancellation for the prevention of disorders in the composition of the intestinal microflora. Hilak® forte is characterized by high efficiency and good tolerability. No contraindications to prescribing the drug and side effects have been identified; it can be prescribed not only for adults, but also for infants. Hilak® forte is recommended to be taken orally before or during meals, diluted with a small amount of liquid (water should not have an alkaline reaction!). The initial dose for adults is 40-60 drops 3 times a day; for children - 20-40 drops 3 times a day; for infants - 15-30 drops 3 times a day. As clinical improvement occurs, the dose may be reduced by half. Hilak® forte should not be taken at the same time as antacids and adsorbents, since antacids neutralize and adsorbents reduce the bioavailability of the acids that make up the drug.

As a long-term prebiotic (up to 6 months), lactulose (Duphalac, Abbott Biologicals, Netherlands) can be used at a prebiotic dose of 5-10 ml per day. Lactulose is a classic active prebiotic, or bifidus factor, a unique carbohydrate found in human milk. In the intestine, lactulose becomes an ideal nutrient substrate for saccharolytic bacteria (bifido- and lactobacilli).

Thus, for the diagnosis of SIBO in patients, it is advisable to prescribe hydrogen breath tests with lactulose, glucose, lactose, and other sugars along with other standard examination methods. To correct SIBO, in addition to selective decontamination of pathogenic and opportunistic microflora (if necessary), it is very important to restore the normal microbial landscape of the intestine using prebiotics and probiotics, including metabolite probiotics.

Literature

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E. Yu. Plotnikova*, doctor of medical sciences, professor
M. V. Borsch**
M. V. Krasnova***,Candidate of Medical Sciences
E. N. Baranova*

* GBOU VPO KemGMA Ministry of Health of the Russian Federation, Kemerovo,
** MBLPU City Clinical Hospital No. 1, Novokuznetsk,
***Kuzbass Regional Hepatological Center MBUZ City Clinical Hospital No. 3 named after. M. A. Podgorbunsky, Kemerovo

In this case, symptoms of impaired absorption of vitamins, nutrients appear and body weight decreases.

Excessive bacterial growth in the small intestine can be observed with violations of the structure and motility of the gastrointestinal tract, as well as a decrease in the secretion of hydrochloric acid. In this case, hypovitaminosis, malabsorption of fats, trophological insufficiency can develop. The diagnosis is confirmed by a breath test or a quantitative culture of small bowel aspirate. Treatment involves oral antibiotics.

In a healthy person, the proximal small intestine contains< 105 бактерий/мл содержимого, преимущественно грамположительные аэробные бактерии. Достаточно низкое содержание бактерий обеспечивается нормальной перистальтической активностью, секрецией соляной кислоты, выработкой слизи, IgA и функцией илеоцекального клапана.

Causes and pathophysiology of intestinal bacterial overgrowth syndrome

Anatomical disorders of the stomach and / or small intestine contribute to the stagnation of the contents and the development of excessive bacterial growth. Conditions accompanied by anatomical changes include diverticulosis of the small intestine, surgically formed blind loops, stomach surgery, strictures, and partial obstruction. Intestinal motility disorders in diabetic neuropathy, amyloidosis, hypothyroidism, idiopathic intestinal pseudo-obstruction also alter bacterial clearance.

Bacteria consume nutrients in excess, incl. carbohydrates and vitamin B 12 , resulting in energy and vitamin B 12 deficiencies. Due to the excess production of folate by bacteria, deficiency of this vitamin is rare. Bacteria cause deconjugation of bile acids, which is accompanied by a violation of the formation of micelles and malabsorption of fats. Fat malabsorption and mucosal damage are accompanied by diarrhea.

The pathogenesis includes the following points:

• Malabsorption of fats, proteins, carbohydrates and vitamins leads to a weakening of the functions of enterocytes and bacterial transformation of nutrients to non-absorbable and toxic metabolites.
• Anaerobes cause deconjugation of bile acids, which turns them off from digestion, while their enterohepatic circulation is disturbed. Deconjugated bile acids contribute to loose, watery stools.
• Intolerance to hydrocarbons develops due to a decrease in the activity of disaccharidases in the brush border: as a result, an increasing amount of osmotically active fragments of hydrocarbons contributes to the pathogenesis of diarrhea associated with excessive proliferation of the bacterial flora.
• Anaerobes compete with the host for vitamin B12. As a result, a deficiency of vitamin B 12 is gradually formed, macrocytic anemia develops.

Causes of excessive proliferation of bacteria

Weakening of host defenses:

• Hypogammaglobulinemia.
• Immunodeficiency (for example, due to HIV).
• Elderly age.
• Chronic pancreatitis.

Excessive entry of bacteria into the small intestine:

• Atrophic gastritis (for example, due to the use of proton pump inhibitors).
• Gastrojejunostomy.
• Resection of the stomach.
• Intestinal fistulas. Decreased clearance of the small intestine.
• Strictures (with Crohn's disease, after surgical interventions).
• Pseudo-obstruction.
• Amyloidosis.
• Autonomic neuropathy (with diabetes, after vagotomy, etc.).

Some Specific Causes of Microflora Overgrowth

Diverticulosis of the jejunum

It is sometimes detected when examining the passage of barium sulfate in patients older than 50 years. The disease is usually asymptomatic, but predisposes to increased bacterial growth and subsequent malabsorption. Rarely, diverticula can cause acute or chronic gastrointestinal bleeding, obstruction, or perforation.

diabetic diarrhea

It occurs as a result of diabetic autonomic neuropathy, which reduces the mobility of the small intestine and affects the secretory function of enterocytes. In some patients with diabetes, concomitant pancreatic insufficiency or celiac disease may be the cause. The diarrhea is watery and may be persistent or alternate with constipation, more pronounced at night, often associated with fecal incontinence, and refractoriness to antidiarrheal drugs is possible. Antibiotic treatment can be effective, but antidiarrheal drugs (diphenoxylate or loperamide) or opiates are often needed. In some patients, the use of the α 2 -adrenergic agonist clonidine (50-100 micrograms every 8 hours) or a somatostatin analogue is effective. Systemic progressive sclerosis (scleroderma) Circular and longitudinal muscular layers of the intestine are fibrosed, its mobility is disturbed, malabsorption is often detected due to increased bacterial growth.

Hypogammaglobulinemia

This rare disease is characterized by a significant decrease or absence of IgA and IgM in serum and jejunal secretions. Patients often suffer from chronic diarrhea, malabsorption, and respiratory infections. Diarrhea occurs due to increased bacterial growth and recurrent gastrointestinal infections (especially giardiasis).

Diagnosis is by determination of serum immunoglobulins and an intestinal biopsy showing a decrease or absence of plasma cells and nodules of lymphoid tissue (nodular lymphoid hyperplasia). Some patients develop villous atrophy. Treatment includes prevention of giardiasis and, if necessary, regular parenteral replacement of immunoglobulins.

Symptoms and signs of intestinal bacterial overgrowth syndrome

The clinical picture consists of diarrhea and weight loss. Possible neurological disorders associated with vitamin B 12 deficiency, abdominal pain and symptoms of impaired absorption of fat-soluble vitamins A, D, E, K.

Many patients are asymptomatic or have only weight loss or signs of nutritional deficiencies. The most typical symptoms are abdominal discomfort, diarrhea, bloating, and excessive gas. In some cases, diarrhea or steatorrhea is severe.

Diagnosis of intestinal bacterial overgrowth syndrome

• 14C xylose breath test or culture culture of small bowel aspirate with quantification.
• In some cases, radiography of the upper gastrointestinal tract with a study of the passage of barium through the small intestine.

The most direct method is culture of aspirate from the duodenum: more than 105 colonies / ml are detected. Less invasive breath tests. To detect malabsorption of bile acids, a sample with homotaurocholic acid labeled with selenium (75 Se) is indicative.

Some experts believe that empiric antibiotic therapy can be considered as a diagnostic test. But since the manifestations of bacterial overgrowth can be similar to those of diseases that occur with the syndrome of malabsorption (for example, Crohn's disease), and the side effects of antibiotics can aggravate the picture of the disease, it is preferable to first establish the etiology of the process.

The standard of diagnosis is culture and quantification of aspirate from the small intestine, in which bacterial growth > 105/mL is detected. However, this analysis requires endoscopy. Breath tests using substrates such as glucose, lactulose, xylose are non-invasive and easy to perform. The 14 C-xylose breath test appears to be the most optimal of all.

If anatomical changes are noted that are not associated with surgical interventions, an x-ray of the upper gastrointestinal tract with a study of the passage of barium through the small intestine should be performed to evaluate them.

Treatment of intestinal bacterial overgrowth syndrome

• Oral administration of antibiotics (various).
• Changes in the nature of nutrition.

Treatment involves the appointment of oral antibiotics for 10-14 days, the spectrum of action of which overlaps aerobic and anaerobic intestinal bacteria. Empiric therapy involves the choice of one of the following regimens: tetracycline, amoxicillin/clavulanic acid, cephalexin, trimethoprim/sulfamethoxazole, metronidazole, rifaximin. If symptoms return, courses of antibiotic treatment may be repeated; changes are based on culture results and susceptibility data. However, changing the antibiotic regimen can be difficult due to the simultaneous presence of many types of bacteria.

Since bacteria in the intestinal lumen metabolize mainly carbohydrates and not fats, a diet low in carbohydrates and dietary fiber and high in fats is preferred.

It is necessary to treat underlying disorders and replenish nutrient deficiencies (in particular, vitamin B 12).

If surgical correction of the underlying disorders leading to stasis is not possible, the main thing in therapy is the use of antibiotics and the elimination of motor function disorders. Antibiotic regimens are usually empirical. Traditionally, tetracycline is considered the drug of choice, it is prescribed 250 mg 4 times a day. Alternatives are amoxicillin + clavulanic acid (Augmentin), Cotrimoxazole [sulfamethoxazole + trimethoprim] and ciprofloxacin. Often a single 7-10-day course eliminates symptoms for several months. In the future, it is necessary to follow the principle of rotation of antibiotics. So far, trials of probiotics have not given positive results or have provided data that do not allow drawing unambiguous conclusions.