Functional gastrointestinal disorders in the Roman definition of criteria IV

The official presentation of the Roman criteria IV took place on 22 may 2016 at the 52nd American gastroenterological week (San Diego, USA).

According to the definition of Roman IV criteria, functional disorders of the gastrointestinal tract (GIT) constitute a violation of the intestinal-brain interaction.

This is a group of disorders, the classification of which is based on clinical symptoms, interconnected in any combination: impaired motility, visceral hypersensitivity, immune dysfunction, altered function of the intestinal mucosa, changes in the microflora of the intestine, disruption of the Central nervous system.

In the Roman criteria IV (2016) formulated the paradigm of the pathogenesis of functional gastrointestinal disorders (fhir) as a consequence of stress effects in violation of the ties along the axis of “brain – gut”, including at the level of immune regulation, regulation of the sensitivity of the intestinal flora, and other components included in the definition depending on leading (leading), in this (specific) clinical situation.

The axis of “brain – gut” is a branched bi-directional communication network (tab. 1), which by neuroimmune-endocrine mediators, monitors and integration of the functions of the gastrointestinal tract, implements the communication of emotional and cognitive centers of the gastrointestinal tract (in terms of its functional activity), coordinating local adaptive reactions to stress factors of any kind. In turn viscerosomatic sensory effects are perceived by the brain and affect pain sensation, mood and behavior.

Under the control of this bi-directional flow axis of all major processes occurring in the digestive tract: motility, secretion, activity and reproduction of intestinal flora, absorption, and migration of flora, microcirculation, local immune defense, cell proliferation. Pathological (disturbed) activity of this system and the violation of functional relationships between its structures constitute the pathophysiological basis fhir. Depending on the leading pathophysiological mechanism (mechanisms) is the basis of the pharmacological, dietary and other therapeutic effects.

In the definition of fhir, the Roman criteria. IV, added section “Intestinal microenvironment and functional gastrointestinal disorders” that share our knowledge about the microbiome, food, nutrition, and which are important not only for understanding the processes occurring in the digestive tract, but also for the impact on this component fhir.

The gastrointestinal microbiota is a dense biological community, comprising approximately 1014 bacteria, weighing more than 1 kg which can be considered as independent in vitro human body (the microbiome) that participates in a metabolic, immunological, protective and digestive processes and affect the state of other organs and systems, and in General on human health.

Gut microbiota includes around 400 different types of bacteria, are organized into three Interative:

• with a predominance of Bacteroides;
• with a predominance of Prevotella;
• with a predominance of Ruminococcus.

A large part of the microbiota is fixed to receptors of the mucosa, a small part is in a free state.

The microbiota of the gastrointestinal tract is very important in terms of functionality. With her participation synthesize some vitamins (mostly b group), are metabolized to bile acids, the degradation of xenobiotics, supports energy homeostasis is supported by local and General immune status: the transformation of lymphocytes, activation of anti-inflammatory cytokines, suppression of Pro-inflammatory cytokines, activates the production of IgA, increases the tolerance of the mucosa to microbial aggression and toxins.

Intestinal microbiocenosis is a highly organized ecosystem, reacting qualitative and quantitative changes in the dynamic state of the human body in various conditions of life. It varies in composition in different parts of the gastrointestinal tract. Thus, in the normal proximal small intestine bacterial content does not exceed 10⁴-10⁵ CFU in 1 ml of aspirate. The content of anaerobic bacteria in the digestive tract increases sequentially toward the distal division. Imbalance of the intestinal microbiota, both quantitative and qualitative, can affect the GI tract. One of these disorders is bacterial overgrowth syndrome (SIBR) 2.

Microbiological criterion overgrowth of bacteria in the small intestine is the presence of microorganisms (E. coli and strains of obligate anaerobes: Bacteroides, clostridia and other), in concentrations greater than 10⁵ CFU in 1 ml aspirate from the jejunum 1.

The reasons for the development SIBR a lot, but if we talk about fhir, it should be noted that they contribute to the development of motor disorders of the gastrointestinal tract, stasis of intestinal contents, impaired function of the ileocecal valve, depression of functional activity of the stomach and immune disorders (radiation exposure, immunosuppressive therapy) 3-7.

Diagnosis SYBR

Gold standard for the diagnosis SIBR is seeding, aspirate the small intestine, but this method has significant performance costs, and in the practice of medicine is not being used.

By far the most simple and affordable and suitable practices are hydrogen breath tests (VDT). They allow you to make a judgment about the presence SIBR for the determination of the concentration of hydrogen in the exhaled air.

In the conduct of VDT use either glucose or lactulose, which is decomposed and recycled microbial flora with the formation of hydrogen, which is absorbed into the blood and excreted in expired air. When SIBR in the small intestine, the concentration of hydrogen increases, and its level, suggesting the presence of SYBR and its severity.

Clinical manifestations are formed by local (intestinal) symptoms and systemic disorders caused by translocation of bacteria and their toxins in the internal environment of the body (malabsorption, immunological disorders, loss of electrolytes, etc.). Thus, when contamination of the upper gastrointestinal tract develops the clinical picture of duodenitis with duodenal hypertension complicating passage of secretions from the liver, pancreas and digestive disorders, reactive mezadenita, biliary disorders. If contaminated lower parts of the small intestine develops abdominal distension, pain, reduced activity of digestive enzymes, occurs indigestion, decreased body weight.

The results of their research

We assessed the violation intestinal microbiocenosis due to excessive colonization of the intestine in patients with chronic pancreatitis with exocrine pancreatic insufficiency: treatment also enzyme preparations include drugs to eliminate the violation of microbiocenosis of the intestine (i.e., preparations of Pro – and prebiotic) 8, 9. Preference is given to preparations with prebiotic properties that stimulate in contrast to probiotics, a change of its own microflora, to avoid antigenic load 10.

In this respect, have the advantage of metabolite – i.e. preparations containing the metabolic products or structural components of probiotic microorganisms. One of the famous representatives of this group of drugs is a complex metabolic Battistin that contains the waste products of Bacillus subtilis (Bacillus subtilis, gram-positive, spore-forming aerobic bacteria), which is an antagonist of microorganisms: Salmonella, Proteus, staphylococci, streptococci, yeast. It produces several types of metabolites: the metabolites with antibacterial activity against the mentioned microorganisms; metabolites with enzymatic activity that are involved in digestion.

The second component of Battistina is sorbitol “zeolite”, which, showing the sorption properties of the compounds of low molecular weight (methane, hydrogen sulfide, ammonia and other toxic substances), reduces various types of intoxication. The third is the hydrolysate of soy flour as a source of amino acids and oligosahara. In General the drug is considered as a stimulator of growth and reproduction of its own normal microflora of the intestine (primarily “obligatory”).

The present study focuses on evaluating the effectiveness of Battistina patients with SYBR the small intestine, which developed on the background exocrine pancreatic insufficiency (the pancreas). Treatment wore combined character: used Battistin and Armidale.

Materials and methods

Studied 78 patients suffering from chronic pancreatitis. 48 of them had insufficiency of the exocrine functions of the pancreas established for the study of elastase 1 in feces (31 had moderate and 17 severe).

In 30 patients the microbial flora was studied by carrying out bacteriological examination of faeces source and in the dynamics of treatment and also studied short-chain fatty acids (SHQ) (C2-C6) in biological substrates took place by gas-liquid chromatographic analysis is also original and in dynamics of treatment.

Microbial flora of the small intestine was studied in 48 patients with the aim of establishing SYBR hydrogen breath test with lactulose. It was also evaluated the clinical manifestations, biochemical data of the study, the General analysis of blood, karbanova sample source and dynamics.

Patients were divided into groups.

• The 1st group consisted of 15 patients who received Ermetal in an adequate dose and Battistin.
• The 2nd group consisted of 15 patients who received Armetal (in severe functional insufficiency of the pancreas – 144 UNITS for lipase activity – 6 patients and 108 UNITS in moderate pancreatic insufficiency – 9 patients).

In groups dominated by men – 2:1, the average age of patients was 48 ± 3,07 years. Chronic alcoholic pancreatitis had 20 patients, biliarsky – 6 and idiopathic 4 people. The groups were matched for sex, age, etiology and course of chronic pancreatitis (CP). Evaluation criteria were: the dynamics of the clinic, intestinal motility (for karbolovoj the sample), state of dysbiosis.

• The 3rd group was 16 patients with chronic pyelonephritis and SYBR who received Battistin and Armidale.
• The 4th group was 16 patients with chronic pyelonephritis and SYBR who received Armetal.
• The 5th group was 16 CP patients that were matched from the archive, not received therapy with study drugs but had the original SIBR and were evaluated in the dynamics.

Battistin (except for patients 5) patients received a stable dose of 2 capsules 2 times a day, for 21 days. Armetale, received the dose, dependent on the degree of exocrine insufficiency of the pancreas in the constant mode, 5-I group – “control” – the initial therapy received.

Statistical processing of the studied parameters was performed using the software package of statistical analysis Statistica 7.0 for Windows 7 and Microsoft Office 2010. To determine the significance of mean values were calculated by t-criteria of student. To assess the reliability of differences used alternative bilateral analysis and Fisher’s χ² with Yates correction for small numbers. Differences were considered significant at value p < 0.05.

The results of the study

The 1st and 2nd group, only 30 patients (15 in each group). On bacteriological research has dysbiosis I–II. furthermore, the studied metabolites (SHQ) of the intestinal microflora. The original data and the results of treatment are presented in table. 2, 3.

From the table it is clear that the treatment was effective: the main symptoms were cropped to 7-11 days with a clear trend of recovery of motility (shortening of the transit time in the constipation and elongation diarrhea); according to the SHQ noted a clear trend towards the restoration of dysbiosis, moreover, with the normalization of profile SHQ in patients receiving combination therapy (Armidale + Battistini). As the recovery eubioz in patients with moderate enzyme deficiency failed to reduce the dose Armidale that was associated with increased levels of fecal elastase 1.

The General conclusion for this section of the study is as follows:

1. Battistinis effective for restoration of intestinal microbiocenosis in patients with exocrine insufficiency of the pancreas (with the concomitant treatment with enzyme preparations).
2. Combined therapy (Battistini and Armidale) allows to reduce the dose of enzyme preparations. This is confirmed by the increased levels of elastase stool, motility and relief of clinical manifestations.

3-I group – 16 patients with chronic pancreatitis who developed SIBR.

Dominated men – 10/6, the mean age was 46 ± 4,03 years, disease duration 8 years, men have dominated the alcoholic form – 9, women biliarsky pancreatitis – 5; 2 patients had idiopathic form.

The duration of treatment was 3 weeks, received Battistin (2 capsules 2 times a day per day), Armidale 72 thousand UNITS (as the drug involved in the formation of functional rest the pancreas, reducing intra-abdominal pressure and the secret passage through the ducts of the pancreas).

4-I group – 16 patients with chronic pancreatitis in remission, but with the presence SIBR, who have formed clinical manifestations: rapid saturation, heaviness after eating, unstable stool (constipation-predominant).

The patients ‘ age 48 ± 7 years, men dominated – 11/5 and alcohol and bioerosive form – 10/4, the duration of illness is 8 years. SIBR had a moderate form of severity.

Patients received, Ermetal in a daily dose of 72 IU the lipase. The duration of treatment was 21 days.

5th group (control), 16 CP patients, who were recruited from the archive. The criterion of selection was SIBR moderate and light severity. Treatment for this reason, before selection of patients was not undertaken. Patients were assessed in the dynamics with the difference in the timing of examination is 21 days. Since patients were in remission, pharmacotherapy about HP not received.

Why chronic pancreatitis is accompanied by the development SIBR? This contributes two circumstances. First, in the period of exacerbation is developing or that the degree of enzyme deficiency. Secondly, in the treatment of KHP used blockers of gastric secretion, which remove the acid barrier of the stomach, opening a window in the lower divisions of the microflora of the oropharynx, stomach and respiratory tract.

The composition of the microflora, which migrates to the duodenum are presented in table. 4 and 5.

This range does not contradict the influence of enzyme and antimicrobial – Battistina.

As a result of treatment in patients of the 3rd group receiving Battistin and Armidale, in 7-10 days the pain was completely or mostly cropped. Clinical symptoms: recovered chair, or significantly ubedilsya with a tendency to the skin, lengthened transit time in patients with a tendency to diarrhoea and decreased transit time in patients with constipation-predominant (9-26 hours, 48-16 hours).

SIBR was docked in 87% of patients. In the 4th group of patients who received only Armetal, clinical symptoms are formed due to disrupted microbial spectrum, which led to duodenostasis, violation of passage of bile and pancreatic secretions. Relief of symptoms occurred in more remote periods of 14-15 days. In some patients, the symptoms decreased, but not completely eliminated, the maximum decreased intestinal dyspepsia (bloating, rumbling, stool frequency). SIBR was docked 50% of patients; in 25% decrease in the intensity of symptoms and in 25% of cases – is preserved in the source extent.

Sick 5th of the control group who received no pharmacotherapy, SYBR preserved in its original state.

Thus, in patients with chronic pancreatitis, develops SIBR, the occurrence of which involves two pathogenic factors:

1. The use of blockers of gastric secretion in the period of exacerbation.
2. Transient violation of the functional activity of the pancreas (enzyme deficiency) that develops in acute HP.

Development SIBR in CP patients accompanied by clinical symptoms (worsening of the main clinic, the slower it mild or the appearance of clinical manifestations in gastric and/or intestinal dyspepsia).

Use in the treatment of disturbed microbiocenosis of Battistina in combination with enzyme preparations (Armetale) leads to the restoration of microbiocenosis in 87% of patients, only the enzyme therapy relieves SYBR 50% of patients. The lack of drug effects saves SIBR leads to its progression and contributes to the exacerbation of chronic pancreatitis.

From the presented data we can draw the following conclusion:

1. Battistinis effective for the restoration of microbiocenosis of the colon in patients with exocrine pancreatic insufficiency.
2. The combined use of Battistina and Armidale allows to reduce the dose of enzyme preparations. This is accompanied by the recovery of microbiocenosis, motor skills and speeds up the relief of the intestinal symptoms.
3. Enzyme preparations (Armetale) is effectively cropped SYBR 50% of patients with chronic pancreatitis.
4. Combined therapy (Battistini + Ermetal) eliminates SYBR 87% of patients with chronic pancreatitis, which is accompanied by relief clinic, motility and shortens the period of active treatment.

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