Аннотация
Введение. Микробиота кишечника ассоциирована с большим количеством заболеваний, в том числе с эндометриозом (эстро-
гензависимым патологическим процессом). Дисбиоз кишечника связан с нарушением метаболизма эстрогенов, однако иссле-
дований, направленных на изучение состава микробиоты при эндометриозе остается достаточно мало.
Цель исследования — оценка особенности таксономического состава пристеночной микробиоты прямой кишки у женщин
репродуктивного возраста с разными стадиями генитального эндометриоза.
Материал и методы. В исследовании приняли участие 43 женщины репродуктивного возраста с подтвержденным на-
ружным генитальным эндометриозом. В зависимости от стадии НГЭ все женщины разделены на три группы: 1-я группа
– женщины с НГЭ I и II стадии (n=7); 2-я группа – женщины с III стадией НГЭ (n=18); 3-я группа – женщины с IV стадией
НГЭ (n=18). Исследование состава пристеночной микробиоты прямой кишки проводилось с использованием полимеразной
цепной реакции в реальном времени.
Результаты. У всех обследованных пациенток в отделяемом слизистой оболочки прямой кишки выявлены микроорганизмы,
являющиеся представителями основных значимых филумов кишечной микробиоты: Actinomycetota, Bacillota, Bacteroidota,
Pseudomonadota, Verrucomicrobiota, Fusobacteriota, Euryarchaeota, и грибы рода Candida. При сравнении частоты выявления
и концентрации различных микроорганизмов в трех группах женщин статистически значимые различия установлены толь-
ко для Methanobrevibacter spp., обнаруженных у женщин 2-й и 3-й групп (p<0,05). Факторы патогенности, к которым отно-
сится выявление Clostridioides difficile с продукцией энтеротоксинов А (tcdA) и B (tcdB), Staphylococcus aureus с геном мети-
циллинрезистентности (mecA), Streptococcus agalactiae с геном инвазивности (srr2) не различались в сравниваемых группах.
Заключение. Профили пристеночной микробиоты кишечника у женщин разных стадий эндометриоза не имели существен-
ных различий. Необходимы дальнейшие исследования для установления роли микробиоты кишечника в патогенезе эндоме-
триоза.
Annotation
Introduction. The gut microbiota is associated with a large number of diseases, including endometriosis (an estrogen-dependent
pathologic process). Dysbiosis in the gut is associated with impaired estrogen metabolism; however, studies aimed at investigating the
composition of the microbiota in endometriosis remain rather scarce.
The aim of this study was to evaluate the peculiarities of the taxonomic composition of the rectal microbiota in women of reproductive
age with different stages of genital endometriosis.
Material and methods. Forty-three women of reproductive age with confirmed external genital endometriosis participated in the
study. Depending on the stage of genital endometriosis all women were divided into three groups: Group 1 — women with stage I and
II genital endometriosis (n=7); Group 2 — women with stage III genital endometriosis (n=18); Group 3 — women with stage IV genital
endometriosis (n=18). The composition of the parietal microbiota of the rectum was studied using real-time polymerase chain reaction.
Results. Microorganisms representing the main significant phyla of the intestinal microbiota: Actinomycetota, Bacillota, Bacteroidota,
Pseudomonadota, Verrucomicrobiota, Fusobacteriota, Euryarchaeota, as well as fungi of the genus Candida were detected in the rectal
mucosal secretions of all examined patients. When comparing the frequency of detection and concentration of different microorganisms
in the three groups of women, a statistically significant difference was found only for Methanobrevibacter spp. detected in women of
the second and third groups (p<0.05). Pathogenicity and virulence factors, which include detection of Clostridioides difficile with
enterotoxins A (tcdA) and B (tcdB), Staphylococcus aureus with methicillin resistance gene (mecA) and Streptococcus agalactiae with
invasiveness gene (srr2) also did not differ in the compared groups.
Conclusion. Profiles of the gut wall microbiota in women of different stages of endometriosis had no significant differences. Further
studies are needed to establish the role of gut microbiota in the pathogenesis of endometriosis.
Key words: genital endometriosis; parietal rectal microbiota; rectum
Список литературы
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R E F E R E NC E S
1. Harder C., Velho R.V., Brandes I., Sehouli J., Mechsner S. Assessing
the true prevalence of endometriosis: A narrative review of literature
data. Int. J. Gynaecol. Obstet. 2024; 167 (3): 883-900. DOI: 10.1002/
ijgo.15756.
2. Khine Y.M., Taniguchi F., Harada T. Clinical management of endometriosis-
associated infertility. Reprod. Med. Biol. 2016; 15 (4): 217-25.
DOI: 10.1007/s12522-016-0237-9.
3. Sachedina A., Todd N. Dysmenorrhea, endometriosis and chronic pelvic
pain in adolescents. J. Clin. Res. Pediatr. Endocrinol. 2020; 12 (1):
7-17. DOI: 10.4274/jcrpe.galenos.2019.2019.S0217.
4. Chen P., Wang D.B., Liang Y.M. Evaluation of estrogen in endometriosis
patients: regulation of GATA-3 in endometrial cells and effects on Th2
cytokines. J. Obstet. Gynaecol. Res. 2016; 42 (6): 669–77. DOI:
10.1111/jog.12957.
5. Bao C., Wang H., Fang H. Genomic evidence supports the recognition
of endometriosis as an Inflammatory systemic disease and reveals
diseasespecific therapeutic potentials of targeting neutrophil
degranulation. Front. Immunol. 2022; 13: 758440. DOI: 10.3389/
fimmu.2022.758440.
6. Pašalić E., Tambuwala M.M., Hromić-Jahjefendić A. Endometriosis:
Classification, pathophysiology, and treatment options. Pathol. Res.
Pract. 2023; 251: 154847. DOI: 10.1016/j.prp.2023.154847.
7. Khan K.N., Kitajima M., Imamura T., Hiraki K., Fujishita A., Sekine I.
et al. Toll-like receptor 4-mediated growth of endometriosis by human
heat-shock protein 70. Hum. Reprod. 2008; 23 (10): 2210–9. DOI:
10.1093/humrep/den195.
8. Lynch S.V., Pedersen O. The human intestinal microbiome in health
and disease. N. Engl. J. Med. 2016; 375 (24): 2369-79. DOI: 10.1056/
NEJMra1600266.
9. Di Vincenzo F., Del Gaudio A., Petito V., Lopetuso L.R., Scaldaferri
F. Gut microbiota, intestinal permeability, and systemic inflammation:
a narrative review. Intern. Emerg. Med. 2024; 19 (2): 275-93. DOI:
10.1007/s11739-023-03374-w.
10. Rinninella E., Raoul P., Cintoni M., Franceschi F., Miggiano
G.A.D., Gasbarrini A. et al. What is the healthy gut microbiota
composition? A changing ecosystem across age, environment, diet,
and diseases. Microorganisms. 2019; 7 (1): 14. DOI: 10.3390/
microorganisms7010014.
11. Fan Y., Pedersen O. Gut microbiota in human metabolic health and
disease. Nat. Rev. Microbiol. 2021; 19 (1): 55-71. DOI: 10.1038/
s41579-020-0433-9.
12. Hantschel J., Weis S., Schäfer K.H., Menger M.D., Kohl M., Egert M.
et al. Effect of endometriosis on the fecal bacteriota composition of
mice during the acute phase of lesion formation. PLoS One. 2019; 14
(12): e0226835. DOI: 10.1371/journal.pone.0226835.
13. Perrotta A.R., Borrelli G.M., Martins C.O., Kallas E.G., Sanabani S.S.,
Griffith L.G. et al. The vaginal microbiome as a tool to predict rASRM
stage of disease in endometriosis: a pilot study. Reprod. Sci. 2020; 27
(4): 1064-73. DOI: 10.1007/s43032-019-00113-5.
14. Ata B., Yildiz S., Turkgeldi E., Brocal V.P., Dinleyici E.C, Moya A.
et al. The endobiota study: comparison of vaginal, cervical and gut
microbiota between women with stage 3/4 endometriosis and healthy
controls. Sci. Rep. 2019; 9 (1): 2204. DOI: 10.1038/s41598-019-
39700-6.
15. Huang L., Liu B., Liu Z., Feng W., Liu M., Wang Y. et.al. Gut microbiota
exceeds cervical microbiota for early diagnosis of endometriosis.
Front. Cell. Infect. Microbiol. 2021; 11: 788836. DOI: 10.3389/
fcimb.2021.788836.
16. Svensson A., Brunkwall L., Roth B., Orho-Melander M., Ohlsson B.
Associations between endometriosis and gut microbiota. Reprod. Sci.
2021; 28 (8): 2367-77. DOI: 10.1007/s43032-021-00506-5.
17. Shan J., Ni Z., Cheng W., Zhou L., Zhai D., Sun S. et.al. Gut microbiota
imbalance and its correlations with hormone and inflammatory factors
in patients with stage 3/4 endometriosis. Arch. Gynecol. Obstet. 2021;
304 (5): 1363-73. DOI: 10.1007/s00404-021-06057-z.
18. Salliss M.E., Farland L.V., Mahnert N.D., Herbst-Kralovetz M.M. The
role of gut and genital microbiota and the estrobolome in endometriosis,
infertility and chronic pelvic pain. Hum. Reprod. Update. 2021; 28 (1):
92-131. DOI: 10.1093/humupd/dmab035.
19. Baker J.M., Al-Nakkash L., Herbst-Kralovetz M.M. Estrogen-gut
microbiome axis: Physiological and clinical implications. Maturitas.
2017; 103: 45-53. DOI: 10.1016/j.maturitas.2017.06.025.
20. Shelekhova M.S., Modorskaya A.N., Fil’chakova A.N., Grudkova
Yu.V., Raevskiy K.P. Current understanding of the connection between
endometriosis and intestinal microbiocenosis: a literature review.
Rossiyskiy meditsinskiy zhurnal. 2024; 30 (2): 181-90. DOI: 10.17816/
medjrf626841. (in Russian)
21. Uzuner C., Mak J., El-Assaad F., Condous G. The bidirectional
relationship between endometriosis and microbiome. Front. Endocrinol.
(Lausanne). 2023; 14: 1110824. DOI: 10.3389/fendo.2023.1110824.
22. Wei Y., Tan H., Yang R., Yang F., Liu D., Huang B. et.al. Gut dysbiosisderived
β-glucuronidase promotes the development of endometriosis.
Fertil. Steril. 2023; 120 (3 Pt 2): 682-94. DOI: 10.1016/j.
fertnstert.2023.03.032.
23. Cuffaro F., Russo E., Amedei A. endometriosis, pain, and related
psychological disorders: unveiling the interplay among the microbiome,
inflammation, and oxidative stress as a common thread. Int. J. Mol. Sci.
2024; 25 (12): 6473. DOI: 10.3390/ijms25126473.
24. Laschke M.W., Menger M.D. The gut microbiota: a puppet master in
the pathogenesis of endometriosis? Am. J. Obstet. Gynecol. 2016; 215
(1): 68.e1-4. DOI: 10.1016/j.ajog.2016.02.036.
25. Lozupone C.A., Stombaugh J.I., Gordon J.I., Jansson J.K., Knight R.
Diversity, stability and resilience of the human gut microbiota. Nature.
2012; 489 (7415): 220-30. DOI: 10.1038/nature11550.
26. Goodrich J.K., Waters J.L., Poole A.C., Sutter J.L., Koren O., Blekhman
R. et.al. Human genetics shape the gut microbiome. Cell. 2014; 159
(4): 789-99. DOI: 10.1016/j.cell.2014.09.053.
27. Mathur R., Goyal D., Kim G., Barlow G.M., Chua K.S., Pimentel M.
Methane-producing human subjects have higher serum glucose levels
during oral glucose challenge than non-methane producers: a pilot
study of the effects of enteric methanogens on glycemic regulation.
Research Journal of Endocrinology and Metabolism. 2014; 2: 1-5.
28. Spigaglia P. Clostridioides difficile and gut microbiota: from
colonization to infection and treatment. Pathogens. 2024; 13(8): 646.
DOI: 10.3390/pathogens13080646.
29. Ling J., Hryckowian A.J. Re-framing the importance of group B
Streptococcus as a gut-resident pathobiont. Infect. Immun. 2024; 92
(9): e0047823. DOI: 10.1128/iai.00478-23.
30. Liu A., Garrett S., Hong W., Zhang J. Staphylococcus aureus infections
and human intestinal microbiota. Pathogens. 2024; 13(4): 276. DOI:
10.3390/pathogens13040276.
31. Howden B.P., Giulieri S.G., Wong Fok Lung T., Baines S.L., Sharkey
L.K., Lee J.Y.H. et al. Staphylococcus aureus host interactions and
adaptation. Nat. Rev. Microbiol. 2023; 21 (6): 380-95. DOI: 10.1038/
s41579-023-00852-y.
32. Maree M., Thi Nguyen L.T., Ohniwa R.L., Higashide M., Msadek
T., Morikawa K. Natural transformation allows transfer of SCCmecmediated
methicillin resistance in Staphylococcus aureus biofilms. Nat.
Commun. 2022; 13 (1): 2477. DOI: 10.1038/s41467-022-29877-2.
33. Shalepo K.V., Husnutdinova T.A., Budilovskaya O.V., Krysanova A.A.,
Sapozhnikov K.V., Savicheva A.M. Molecular genetic determinants of
virulence of Streptococcus agalactiae isolated from pregnant women
and newborns in St. Petersburg and the Leningrad region in 2010–
2023. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2024;
101: (2): 217-26. DOI: 10.36233/0372-9311-501. (in Russian)