The state of the intestinal microbiocenosis in patients with duodenal peptic ulcer disease under different eradication therapy regimens and evaluation of the efficacy of some new probiotic preparations

The dissertation is devoted to the study of the intestinal microbiocenosis in patients with duodenal peptic ulcer disease under different Helicobacter pylori eradication therapy regimens. It examines the pathogenetic role of Helicobacter infection, the side effects of antibacterial therapy manifested as disturbances of the intestinal microflora, and the possibilities of correcting these disturbances with new probiotic preparations. The work presents the results of clinical and endoscopic examination of patients, health-related quality of life assessment, the morphological state of the mucosal lining of the duodenum and colon, and a comparative analysis of standard eradication regimens and regimens supplemented with probiotics.

The aim of the work is a comparative analysis of the effect of different eradication therapy regimens on the state of the intestinal microbiocenosis and an evaluation of the efficacy of some new probiotic preparations in young patients with peptic ulcer disease. The study formulates tasks on the analysis of clinical symptoms, Helicobacter pylori infection, the dynamics of the microflora and the morphological changes of the mucosal lining, and determines optimal treatment regimens for the combined use of antibacterial and probiotic agents.

Relevance of the problem. Duodenal peptic ulcer disease continues to be one of the pressing problems of modern scientific and practical gastroenterology. Clinical and epidemiological studies have shown that the level of morbidity, disability and life-threatening complications caused by peptic ulcer disease remains high (Grigor'ev P.Ya., 1987; Tkachenko E.I. et al., 1995). The prevalence of gastric and duodenal peptic ulcer disease among the adult population ranges from 6 to 10%. The wide introduction of endoscopic methods for examining the upper gastrointestinal tract has made it possible to stabilise the number of patients suffering from this nosological entity. To date, a sufficient number of works have been published indicating a decrease in the number of relapses of duodenal peptic ulcer disease after successful eradication of Helicobacter infection (Ostrovskii I.M., 1998; Burette A., 1994; Macri G., 1996; Tytgat G.N.J., 1995), with the relapse rate declining to 0–4% (Atherton J.C., 1994; de Boer W.A., 1995; Noach L.A., 1994).

At the same time, it is evident that one of the priority tasks in gastroenterology continues to be the scientific substantiation and practical implementation of optimal eradication therapy regimens that take into account regional and age-related characteristics of patients. At the same time, it has become clear that the administration of eradication therapy is not inconsequential for the patient. In particular, its consequence is the aggravation of disturbances of the intestinal microbiocenosis, changes in which under basal conditions can be detected (according to the data of the Institute of Nutrition of the Russian Academy of Medical Sciences) in 92% of the population. Under these conditions, the use of two broad-spectrum antibacterial agents in the Helicobacter pylori (H.p.) eradication regimens inevitably potentiates their adverse effect on the state of the microbiocenosis and determines the progression of metabolic disturbances.

Current international guidelines provide for the treatment of peptic ulcer disease and erosive lesions of the stomach and duodenum associated with H.p. with medications that predominantly include one of the proton pump inhibitors (PPIs) in combination with two or three antibacterial agents. At the same time, the practical use of such treatment regimens is controversial, since it has led, on the one hand, to a decrease in the frequency of exacerbations and recurrences of peptic ulcer disease and to an improvement in the patients' quality of life, but on the other hand, to the emergence of resistant H.p. strains (Ivashkin V.T. et al., 1999) and, accordingly, to a decrease in the efficacy of basic therapy. Therefore, the development of H.p. resistance to antibiotics is an inevitable phenomenon and is practically difficult to prevent. This in turn stimulates the creation of new antibiotics and the development of new treatment regimens. Under these conditions, the wide use of antibacterial agents as the main option for the treatment of H.p.-associated diseases leads to the development in the majority of patients (over 50%) of such undesirable side effects as gastric dyspepsia and disturbance of the qualitative and quantitative composition of the intestinal microflora. A direct relationship has been traced between the development of these side effects even within a short period after the start of eradication therapy. The objectives of eradication therapy in peptic ulcer disease are not only to reduce the severity of clinical manifestations and to prevent the development of disease recurrence, but also to avoid adverse complications on the part of the gastrointestinal tract. The severity of the disease, its chronic course, complications and the need for an individual approach to each patient make the treatment of peptic ulcer disease a complex problem, and the use of different H.p. eradication regimens to achieve and maintain disease remission also remains relevant. Thus, there is a need to improve standard anti-Helicobacter therapy regimens and to supplement them with preparations whose action would be aimed at preventing and/or alleviating dysbiotic disorders and mobilising the metabolic potential of the normal intestinal microflora.

Aim of the study.

To carry out a comparative analysis of the effect of different eradication therapy regimens on the state of the intestinal microbiocenosis and to evaluate the efficacy of some new probiotic preparations in young patients with peptic ulcer disease.

Tasks of the study

1. To conduct a clinical and endoscopic examination of patients with duodenal peptic ulcer disease with an assessment of Helicobacter pylori infection using the urease test and morphological analysis before and after different therapy variants.

2. To analyse the clinical symptoms of the disease and health-related quality of life in patients with duodenal peptic ulcer disease before and after treatment with standard therapy regimens and analogous therapy supplemented with probiotic preparations.

3. To evaluate the effect of different eradication therapy regimens on the state of the intestinal microflora, and to clarify the features of the intestinal microflora when probiotic preparations are included in the eradication therapy regimens.

4. To study the morphological features of the mucosal lining of the duodenum and colon and their dynamics before and after different therapy variants.

Scientific novelty

For the first time, changes in the intestinal microbiocenosis during the use of different anti-Helicobacter therapy regimens have been studied, and for the first time a clinical evaluation of the efficacy of some new probiotic preparations that correct disturbances of the intestinal microbiocenosis and mobilise the metabolic potential of the intestinal microflora has been carried out. For the first time, through comparative analysis, the morphological state of the mucosal lining of the duodenum and colon has been assessed under different eradication therapy regimens and a decrease in the severity of inflammatory and dystrophic changes has been demonstrated. Ultimately, optimal treatment regimens for patients with peptic ulcer disease have been determined for the combined use of antibacterial and probiotic preparations. The efficacy of the proposed approaches to improving the results of eradication therapy of peptic ulcer disease is corroborated by the assessment of the patients' quality of life at the time of clinical remission of the disease.

Practical significance

The obtained results make it possible to choose optimal eradication therapy regimens for peptic ulcer disease. The safety, expediency and possibility of supplementing standard regimens with probiotic preparations, the action of which is aimed at the prevention or elimination of dysbiotic disorders, have been demonstrated. The supplementation of eradication therapy with probiotic preparations makes it possible to provide prophylaxis of disturbances of the intestinal microbiocenosis and to increase the efficacy of eradication therapy in peptic ulcer disease, actively improves the morphological state of the mucosal lining of the duodenum and colon. Overall, probiotic preparations improve the results of treatment of peptic ulcer disease and the patients' quality of life.

Main propositions put forward for defence

1. Standard eradication therapy of duodenal peptic ulcer disease in combination with probiotic preparations is distinguished by higher clinical efficacy in eliminating the main clinical symptoms, preventing adverse effects and improving the indicators of the overall health-related quality of life. The combination with probiotic preparations makes it possible to arrest inflammatory phenomena and microcirculatory disturbances more effectively and to accelerate the rate of reparation in the mucosal lining of the duodenal bulb and of the distal parts of the colon.

2. Antibacterial therapy as part of standard eradication regimens exerts a negative effect on the state of the representatives of the normal intestinal microflora in patients with peptic ulcer disease, which may be associated with the development of certain adverse effects, in particular nausea and moderately expressed diarrhoea. The inclusion of probiotic preparations in standard eradication therapy regimens makes it possible to avoid the development or aggravation of intestinal dysbiotic disorders.

3. With respect to Helicobacter infection in patients with peptic ulcer disease, probiotic preparations potentiate the eradication effects of antibacterial preparations and reduce the number of patients with persistence of Helicobacter pylori after the main course of treatment.

Approbation and publications

The main propositions of the work were discussed at a meeting of the gastroenterological section of the S.P. Botkin Saint Petersburg Scientific and Practical Society of Therapists (2005). The materials of the study were reported at the 7th Slavic-Baltic Scientific Forum "Saint Petersburg – 2005", the III Saint Petersburg Medical Assembly "Doctor-Pharmacist-Patient" (2005), the Scientific and Practical Conference "New Technologies in the Diagnosis and Treatment of Digestive System Diseases. Topical Issues of Clinical Nutrition in Medical Practice" (2005), the I North-Western Scientific Conference "Probiotics, Prebiotics, Synbiotics. Fundamental and Clinical Aspects", and the 10th Anniversary North-Western Scientific and Practical Conference dedicated to the 70th birthday of Professor E.S. Ryss.

The obtained results have been introduced into the therapeutic, teaching and research processes at the departments of hospital therapy and of naval and hospital therapy of the S.M. Kirov Military Medical Academy, the department of propaedeutics of internal diseases of the I.I. Mechnikov Saint Petersburg Medical Academy, and the gastroenterological centre of the 442nd District Military Clinical Hospital named after Z.P. Solov'ev.

Ten publications have been issued on the topic of the dissertation, including those in editions recommended by the Higher Attestation Commission.