Авторы

  • Хаккулова Марта Алишеровна, Berdieva E'zoza, Sokhibova Shahzoda
    Tashkent state Medical Academy

DOI:

https://doi.org/10.71337/inlibrary.uz.iqro.104242

Аннотация

The immunity of the organism is closely related to the function of the normal microflora, which is currently considered as a peculiar organ of the immune system. This is why maintaining the ecological balance in the gastrointestinal tract is so important. It is known that the loss of normal microflora function, with the subsequent activation of opportunistic pathogens, causes disruptions in both local and systemic immune responses [3,5, 8, 12, 13, 14, 15, 16, 17].


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JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025

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Normal va Pathologist of Physiology Department , Pathologist of Physiology Assistant :

Хаккулова Марта Алишеровна

Students :

Berdieva E'zoza, Sokhibova Shahzoda

Tashkent state Medical Academy

CHARACTERISTICS OF THE PERI-GASTRIC MICROFLORA AND DEGREE OF

GASTRIC DYSBIOSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

The immunity of the organism is closely related to the function of the normal microflora, which

is currently considered as a peculiar organ of the immune system. This is why maintaining the

ecological balance in the gastrointestinal tract is so important. It is known that the loss of normal

microflora function, with the subsequent activation of opportunistic pathogens, causes

disruptions in both local and systemic immune responses [3,5, 8, 12, 13, 14, 15, 16, 17].

The possible role of opportunistic flora as a causative or triggering factor is discussed in the

context of a number of autoimmune diseases: rheumatoid arthritis [10, 11], Bechterew's disease

[2], and systemic vasculitis [7]. Most authors, however, place the greatest emphasis on

exogenous infections, ignoring the role of opportunistic microflora, which can serve as a source

of endogenous infection and a powerful antigenic stimulus [6, 18, 19, 20]. There are few works

that address the state of gastric microflora in the context of immune disturbances in patients with

rheumatoid arthritis (RA). Therefore, identifying the role of gastric microflora in the

development of immune disturbances in RA patients is a relevant task.

Objective of the study

: To examine the state of the mucosal microflora of the stomach in

patients with RA, taking into account the degree of disease activity.

Materials and Methods

: 159 people aged 19 to 83 years were examined. Among the patients,

there were 128 women and 31 men, with a female-to-male ratio of 4.13:1. The average age was

55 ± 0.86 years. The diagnosis of RA was confirmed in all cases according to the criteria of the

American College of Rheumatology [1]. Of the patients, 23 (22.12%) had stage 1 disease activity,

63 (60.58%) had stage IX, and 14 (13.46%) had stage III. According to the course of the disease,

patients were classified as follows: slow-progressing course in 94 (90.38%) patients and rapid-

progressing course in 10 (9.62%) patients.

Joint Form of RA was diagnosed in 95 (100%)

patients. Radiologically, stage I RA was detected in 31 (29.81%), stage II in 46 (44.23%),

stage III in 26 (25.00%), and stage IV in 1 (0.96%) patient.

The study included standard clinical and radiological examinations, microbiological analysis of

stool and urine, endoscopic examination (using an "Olympus" device) of the stomach and

duodenum with biopsy of the mucous membrane, and microbiological examination of the

mucosal biopsy samples (MBS) of the stomach and gastric juice. Isolation and identification of

microorganisms (MOs) were carried out using standard methods. Gastric and duodenal dysbiosis

was characterized according to the criteria proposed by V.V. Chernin and co-authors [9].

Results of the Study

:

When examining the gastric mucosal biopsies of RA patients,

peptostreptococci

were more

frequently isolated in 71.4% of cases, followed by

staphylococci

and

Escherichia coli

in 50%,

Klebsiella

in 42.8%,

streptococci

in 35.7%,

enterococci

and

micrococci

in 21.4%, and more

rarely

Pseudomonas

and

bacilli

in 14.2%.

Candida

yeast-like fungi were found in 8.3% of cases,

with colony counts ranging from 2.77 to 10 lg CFU/g and combinations of 2 to 5 types of

microorganisms.

Figure 1 shows the data on the quantitative characteristics of the peri-gastric microflora.


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Fig. 1. Quantitative characteristics of the peri-gastric microflora of the stomach in patients

with RA

When assessing the colonization of the gastric mucosa in RA patients in quantitative terms, the

following results were obtained:

Klebsiella

were isolated at 10 lg CFU/g,

Pseudomonas

at 8 lg

CFU/g,

Escherichia coli

at 7.47 lg CFU/g,

Streptococci

at 5.7 lg CFU/g,

Enterococci

at 4.33 lg

CFU/g,

Bacilli

at 4.14 lg CFU/g,

Staphylococci

at 3.87 lg CFU/g,

Peptostreptococci

at 3.68 lg

CFU/g,

Micrococci

at 3 lg CFU/g, and

Candida

at 2.77 lg CFU/g.

Therefore, in all examined patients, there was a high level of both resident and opportunistic

microflora, indicating the development of dysbiosis in the mucosal microflora (V.V. Chernin et

al., 2011).

The results of studying the spectrum and frequency of microorganism occurrence depending on

the degree of activity of the joint syndrome are shown in Figure 2.


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Fig. 2. Spectrum and frequency of microorganism occurrence in the mucosal layer in

patients with RA depending on disease activity

In RA patients with stage I disease activity, the following frequency of microorganism

occurrence was found in gastric juice:

Peptostreptococci

– 100%,

Staphylococci

– 80%,

Streptococci

and

Escherichia coli

– 40%,

Bacilli

,

Klebsiella

,

Candida

, and

Enterococci

– 20%.

In RA patients with stage II disease activity, the following frequency of microorganism

occurrence was found in the gastric mucosa: approximately equal proportions of

Escherichia coli

,

Klebsiella

, and

Peptococci

– 55.5%,

Staphylococci

and

Streptococci

– 33.3%,

Enterococci

and

Pseudomonas

– 22.2%,

Bacilli

– 11.1%.

Therefore, in RA patients, the frequency of occurrence of microorganisms characteristic of the

mucosal flora and opportunistic microorganisms slightly decreases as the disease activity

increases.

The quantitative aspects of the mucosal microflora in RA patients were also analyzed depending

on the degree of activity of the inflammatory process in the joints. The data are presented in

Figure 3.

As shown in Figure 3, in RA patients with stage I disease activity,

Klebsiella

were isolated at 12

lg CFU/g,

Streptococci

at 5.03 lg CFU/g,

Staphylococci

at 4.02 lg CFU/g,

Enterococci

at 4 lg

CFU/g,

Peptostreptococci

at 3.39 lg CFU/g,

Bacilli

at 3.14 lg CFU/g,

Candida

at 2.77 lg CFU/g,

and

Escherichia coli

at 2.15 lg CFU/g.


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In patients with stage II disease activity,

Escherichia coli

and

Klebsiella

were isolated at 9.6 lg

CFU/g,

Pseudomonas

at 8 lg CFU/g,

Streptococci

at 6.15 lg CFU/g,

Bacilli

at 5.14 lg CFU/g,

Enterococci

at 4.5 lg CFU/g,

Peptostreptococci

at 3.98 lg CFU/g, and

Staphylococci

at 3.66 lg

CFU/g.

Fig. 3. Quantitative characteristics of the peri-gastric microflora of the stomach in patients with

RA depending on disease activity

Therefore, in general, in RA patients, with an increase in disease activity, there was a

quantitative increase in the number of cultures of both resident mucosal microflora and non-

resident (anaerobic gram-positive cocci, opportunistic flora) microflora, which fits the concept of

mucosal dysbiosis syndrome.

An assessment of the degree of dysbiosis of the mucosal microflora was performed, and the

results are presented in Figure 4.

Fig. 4. Mucosal flora dysbiosis in patients with RA

As seen in the figure, 71.4% of RA patients were found to have mucosal microflora dysbiosis of

varying severity (according to the classification of intra-luminal dysbiosis of the gastroduodenal

zone by E.A. Beyul and I.B. Kuvaeva). The following table presents data on the severity of

dysbiosis of the mucosal microflora depending on disease activity.


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It was established that in RA patients, the severity of dysbiotic shifts in the peri-gastric

microflora increases with the rising degree of activity of the inflammatory process in the joints.

Thus, in patients with stage I RA activity, stage III dysbiosis was found in 20% of patients, while

in patients with stage II RA activity, stage III dysbiosis was found in 55.5% of patients.

The development of gastric dysbiosis manifests as a change in the protective-barrier potential of

this zone, as the microflora of the biotope performs a protective function – colonization

resistance [4]. Another important function of normal microflora is the provision of immune

defense [8]. It is likely that in the condition of dysbiosis, changes occur in the immune defense of

the div, which leads to disruptions in the immune-inflammatory response. Thus, it becomes

evident that the development of dysbiosis in the gastroduodenal zone should have a certain

impact on the course of rheumatoid arthritis, as shown by our research. A clear relationship is

observed between the severity of dysbiosis and the degree of activity of joint pathology. The

higher the activity of joint pathology, the more pronounced the gastric dysbiosis, and vice versa.

Conclusions:

RA patients show dysbiotic changes in the stomach. The severity of dysbiosis is directly

dependent on the activity of joint pathology.

References

1. Arnett F.G., Edworth S.M., Bloch D.A., et al. The American Rheumatism Association 1987

revised criteria for the classification of rheumatoid arthritis.

Arthritis Rheum

1988; 31: 315-324.

2. Bevz N.I. et al. Intestinal microflora in rheumatic diseases.

Antibiotics and Colonization

Resistance

. Moscow, 1990. Vol. 19, pp. 131-135.

3. Vorobyev A.A. et al. Characteristics of the intestinal microflora in infectious endocarditis.

J.

Microbiol., Epidemiol., Immunol.

1996; No. 1, pp. 70-74.

4. Vorobyev A.A., Nesvizhsky Y.V., Lipnitsky E.M. et al. Study of the peri-gastric microflora

of the gastrointestinal tract in humans under normal and pathological conditions.

Vestnik RAMN

2004; 2: 43-47.

5. Loginov A.S., Tsaregorodtsev T.M., Zotin M.M.

Immune System and Diseases of the

Digestive Organs

. Moscow, 1986.

6. Manelis Z.S.

J. Neuropathol. and Psychiatry im. Korsakova.

1986; No. 11, pp. 1720-1726.

7. Osipov G.A., Demina A.M. Chromato-mass spectrometric detection of microorganisms in

anaerobic infectious processes.

Vestnik RAMN

1996; Vol. 13, No. 2, pp. 52-59.

8. Tsoi I.G., Saparov A.S., Timofeev I.K. et al.

J. Microbiol.

1994; No. 6, pp. 112-113.

9. Chernin V.V., Chervinets V.M., Bondarenko V.M., Bazlov S.N.

Dysbiosis of the Mucosal

Microflora of the Esophagogastroduodenal Zone.

Moscow: MIA, 2011.

10. Sheveleva S.A. Probiotics, prebiotics, and probiotic products. Current state of the issue.

Voprosy Pitaniya

1999; No. 2, pp. 32-40.

11. Shenderov B.A.

Medical Microbial Ecology and Functional Nutrition.

Vol. 1: Microflora of

Humans and Animals and Its Functions. Moscow: Grant, 1998.

12. Shiraliyeva R.K. Indicators of cellular and humoral immunity in multiple sclerosis.

Azerb.

Med. J.

1987; No. 5, pp. 46-50.

13. Daugelat S., Kaufman S.H.E. Role of Th-1 and Th-2 cells in bacterial infections.

Chem.

Immunol.

1995; Vol. 63, pp. 66-97.

14. De Freitas E.C., Sandberg-Wolheim M., Schonely H. et al. Regulation of interleukin-2

receptors on T-cells from multiple sclerosis patients.

Proc Nat Acad Sci USA

1986; 83: 2637-

2641.

15. De Simone C., Tzantzoglou S., Baldinelli L. et al.

Immunopharmacology and

Immunotoxicology

1988; Vol. 10, No. 3, pp. 399-415.

Dhib-Jalbut S., McFarlin D.E. Immunology of multiple sclerosis.

Ann Allergy

1990; 64: 433-444.


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JOURNAL OF IQRO – ЖУРНАЛ ИҚРО – IQRO JURNALI – volume 15, issue 02, 2025

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16. Douglas A.P., Weetman A.P.

Digestion

1975; Vol. 13, pp. 344-371.

17. Duggan-Keen M., Roberts D.F., Wentzel J. HLA (Class antigen) status and cell-mediated

immunity in multiple sclerosis.

Acta Neurol Scand

1987; 75: 218-220.

18. Koch-Henriksen N. An epidemiological study of multiple sclerosis.

Acta Neurol Scand

1989;

124 (special Suppl).

19. Koopman J.P., Mullink J.W.M.A., Hectors M.C. Association of germ-free mice with

intestinal microflora obtained from "normal" mice.

Lab. Anim.

1982; No. 16, pp. 59-64.

20. Kurita-Ochiai T., Fukushima K., Ochiai K.

Infect Immun

1997; 65: 1: 35-41.

Библиографические ссылки

Arnett F.G., Edworth S.M., Bloch D.A., et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315-324.

Bevz N.I. et al. Intestinal microflora in rheumatic diseases. Antibiotics and Colonization Resistance. Moscow, 1990. Vol. 19, pp. 131-135.

Vorobyev A.A. et al. Characteristics of the intestinal microflora in infectious endocarditis. J. Microbiol., Epidemiol., Immunol. 1996; No. 1, pp. 70-74.

Vorobyev A.A., Nesvizhsky Y.V., Lipnitsky E.M. et al. Study of the peri-gastric microflora of the gastrointestinal tract in humans under normal and pathological conditions. Vestnik RAMN 2004; 2: 43-47.

Loginov A.S., Tsaregorodtsev T.M., Zotin M.M. Immune System and Diseases of the Digestive Organs. Moscow, 1986.

Manelis Z.S. J. Neuropathol. and Psychiatry im. Korsakova. 1986; No. 11, pp. 1720-1726.

Osipov G.A., Demina A.M. Chromato-mass spectrometric detection of microorganisms in anaerobic infectious processes. Vestnik RAMN 1996; Vol. 13, No. 2, pp. 52-59.

Tsoi I.G., Saparov A.S., Timofeev I.K. et al. J. Microbiol. 1994; No. 6, pp. 112-113.

Chernin V.V., Chervinets V.M., Bondarenko V.M., Bazlov S.N. Dysbiosis of the Mucosal Microflora of the Esophagogastroduodenal Zone. Moscow: MIA, 2011.

Sheveleva S.A. Probiotics, prebiotics, and probiotic products. Current state of the issue. Voprosy Pitaniya 1999; No. 2, pp. 32-40.

Shenderov B.A. Medical Microbial Ecology and Functional Nutrition. Vol. 1: Microflora of Humans and Animals and Its Functions. Moscow: Grant, 1998.

Shiraliyeva R.K. Indicators of cellular and humoral immunity in multiple sclerosis. Azerb. Med. J. 1987; No. 5, pp. 46-50.

Daugelat S., Kaufman S.H.E. Role of Th-1 and Th-2 cells in bacterial infections. Chem. Immunol. 1995; Vol. 63, pp. 66-97.

De Freitas E.C., Sandberg-Wolheim M., Schonely H. et al. Regulation of interleukin-2 receptors on T-cells from multiple sclerosis patients. Proc Nat Acad Sci USA 1986; 83: 2637-2641.

De Simone C., Tzantzoglou S., Baldinelli L. et al. Immunopharmacology and Immunotoxicology 1988; Vol. 10, No. 3, pp. 399-415.

Dhib-Jalbut S., McFarlin D.E. Immunology of multiple sclerosis. Ann Allergy 1990; 64: 433-444.

Douglas A.P., Weetman A.P. Digestion 1975; Vol. 13, pp. 344-371.

Duggan-Keen M., Roberts D.F., Wentzel J. HLA (Class antigen) status and cell-mediated immunity in multiple sclerosis. Acta Neurol Scand 1987; 75: 218-220.

Koch-Henriksen N. An epidemiological study of multiple sclerosis. Acta Neurol Scand 1989; 124 (special Suppl).

Koopman J.P., Mullink J.W.M.A., Hectors M.C. Association of germ-free mice with intestinal microflora obtained from "normal" mice. Lab. Anim. 1982; No. 16, pp. 59-64.

Kurita-Ochiai T., Fukushima K., Ochiai K. Infect Immun 1997; 65: 1: 35-41.