Diagnostical value of intestinal microbiota as one of the leading factors of the development of ulcerative colitis in type 2 diabetes mellitus patients


DOI: https://dx.doi.org/10.18565/therapy.2024.3.7-18

Lagutina S.N., Pashkova A.A., Dudurich V.V., Danilov L.G., Ermachenko E.D.

1) N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia; 2) Serbalab LLC, Saint Petersburg; 3) Saint Petersburg State University
Abstract. Incidence of ulcerative colitis (UC) in the structure of gastroenterological pathology is steadily increasing. Presence of comorbid conditions, including type 2 diabetes mellitus (T2 DM2), contributes to the development of UC complicated forms. The progressive course and resistance to the main groups of drugs lead to disability of the working part of population. The search for new diagnostic markers could help to the timely initiation of therapy, which will shorten time periods for clinical and endoscopic remission.
The aim: to assess the biodiversity of the gut microbiota in patients with UC and T2 DM.
Material and methods. 16S rRNA sequencing of the intestinal microbiota in 100 patients (80 patients with UC and T2 DM2, 20 patients with UC, 20 somatically healthy patients) was performed. Diagnosis of UC was verified using laboratory and instrumental research methods. The average age of the examined groups of patients was 50.1 ± 8.3 years.
Results. The study group was consisted mostly by patients with mild UC. When assessing the intestinal microbiota in patients with UC and T2 DM2, a significantly important increase of quantitative amount of bacterial specimens involved in carbohydrate metabolism (Akkermansia, Dorea, Collinsella, Lachnospira) was fixed. Correlation between representatives of methane producers group and the presence of an inflammatory process in UC, as well as an increase in the opportunistic and pathogenic cluster were found.
Conclusion. An increase of the amount of Firmicutes representatives was found in UC patients comparatively to the control group. At the same time, an increase of the amount of methane-producing bacteria can be one of the non-invasive criteria for assessing the severity of UC with underlying T2 DM2. The obtained data, indicating new potential mechanisms for UC development, can serve as the basis for improving the diagnosis and treatment of this pathology in the presence of comorbid conditions.

Literature


1. Тикунов А.Ю., Морозов В.В., Швалов А.Н. с соавт. Изменение кишечного микробиома пациентов с язвенным колитом после трансплантации кишечной микробиоты. Вавиловский журнал генетики и селекции. 2020; 24(2): 168–175. (Tikunov A.Y., Morozov V.V., Shvalov A.N. et al. Fecal microbiome change in patients with ulcerative colitis after fecal microbiota transplantation. Vavilovskiy zhurnal genetiki i selektsii = Vavilov Journal of Selection Genetics. 2020; 24(2): 168–175 (In Russ.)).


https://doi.org/10.18699/VJ20.610. EDN: LDIGAJ.


2. Ситкин С.И., Вахитов Т.Я., Ткаченко Е.И. с соавт. Микробиота кишечника при язвенном колите и целиакии. Экспериментальная и клиническая гастроэнтерология. 2017; (1): 8–30. (Sitkin S.I., Vakhitov T.Ya., Tkachenko E.I. et al. Gut microbiota in ulcerative colitis and celiac disease. Eksperimentalnaya i klinicheskaya gastroenterologiya = Experimental and Clinical Gastroenterology. 2017; (1): 8–30 (In Russ.)). EDN: ZFVTVN.


3. Лагутина С.Н., Зуйкова А.А. Особенности биоразнообразия кишечной микробиоты у пациентов с воспалительными заболеваниями кишечника и метаболическими нарушениями (обзор литературы). Сибирский журнал клинической и экспериментальной медицины. 2023; 38(2): 57–63. (Lagutina S.N., Zuikova A.A. Features of intestinal microbiota biodiversity in patients with inflammatory intestinal diseases and metabolic disorders (literature review). Sibirskiy zhurnal klinicheskoy i eksperimentalnoy meditsiny = The Siberian Journal of Clinical and Experimental Medicine. 2023; 38(2): 57–63 (In Russ.)).


https://doi.org/10.29001/2073-8552-2023-38-2-57-63. EDN: NERIZC.


4. Купаева В.А., Лоранская И.Д., Болдырева М.Н. Профиль пристеночного и полостного микробиома кишечника пациентов с язвенным колитом. Клиническая фармакология и терапия. 2020; 29(3): 49–54. (Kupaeva V.A., Loranskaya I.D., Boldyreva M.N. Intestinal and fecal microbiome in patients with ulcerative colitis. Klinicheskaya farmakologiya i terapiya = Clinical Pharmacology and Therapy. 2020; 29(3): 49–54 (In Russ.)).


https://doi.org/10.32756/0869-5490-2020-3-49-54. EDN: FYENHN.


5. Ghavami S.B., Rostami E., Sephay A.A. et al. Alterations of the human gut Methanobrevibacter smithii as a biomarker for inflammatory bowel diseases. Microb Pathog. 2018; 117: 285–89.


https://doi.org/10.1016/j.micpath.2018.01.029. PMID: 29477743.


6. Zheng M., Han R., Yuan Y. et al. The role of Akkermansia muciniphila in inflammatory bowel disease: Current knowledge and perspectives. Front Immunol. 2023; 13: 1089600.


https://doi.org/10.3389/fimmu.2022.1089600. PMID: 36685588. PMCID: PMC9853388.


7. Данилова Н.А., Абдулхаков С.Р., Григорьева Т.В. с соавт. Маркеры дисбиоза у пациентов с язвенным колитом и болезнью Крона. Терапевтический архив. 2019; 91(4): 13–20. (Danilova N.A., Abdulkhakov S.R., Grigoryeva T.V. et al. Markers of dysbiosis in patients with ulcerative colitis and Crohn’s disease. Terapevticheskiy arkhiv = Therapeutic Archive. 2019; 91(4): 13–20 (In Russ.)).


https://doi.org/10.26442/00403660.2019.04.000211. EDN: ZERHUD.


8. Лазебник Л.Б., Конев Ю.В. Новое понимание роли микробиоты в патогенезе метаболического синдрома. Consilium Medicum. 2014; 16(8): 77–82. (Lazebnik L.B., Konev Yu.V. New understanding of the role of microbiota in the pathogenesis of metabolic syndrome. Consilium Medicum. 2014; 16(8): 77–82 (In Russ.)). EDN: SNHVPP.


9. Бикбавова Г.Р., Ливзан М.А. Системное воспаление и кардиоваскулярные риски у больных воспалительными заболеваниями кишечника: что необходимо учитывать? Экспериментальная и клиническая гастроэнтерология. 2021; (6): 112–120. (BIkbavova G.R., Livzan M.A. Cardiovascular risks in patients with inflammatory bowel disease: What should be taken into account? Eksperimentalnaya i klinicheskaya gastroenterologiya = Experimental and Clinical Gastroenterology. 2021; (6): 112–120 (In Russ.)).


https://doi.org/10.31146/1682-8658-ecg-190-6-112-120. EDN: LILMEV.


10. Баранцевич Н.Е., Конради А.О., Баранцевич Е.П. Артериальная гипертензия: роль микробиоты кишечника. Артериальная гипертензия. 2019; 25(5): 460–66. (Barantsevich N.E., Konradi A.O., Barantsevich E.P. Arterial hypertension: The role of gut microbiota. Arterial’naya gipertenziya = Arterial Hypertension. 2019; 25(5): 460–66 (In Russ.)).


https://doi.org/10.18705/1607-419X-2019-25-5-460-466. EDN: DTOCTL.


11. Callahan B.J., McMurdie P.J., Rosen M.J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016; 13(7): 581–83.


https://doi.org/10.1038/nmeth.3869. PMID: 27214047. PMCID: PMC4927377.


12. Richterich P. Estimation of errors in “raw” DNA sequences: A validation study. Genome Res. 1998; 8(3): 251–59.


https://doi.org/10.1101/gr.8.3.251. PMID: 9521928. PMCID: PMC310698.


13. Qiong W., Garrity M.G., Tiedje M.J., Cole R.J. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007; 73(16): 5261–67.


https://doi.org/10.1128/AEM.00062-07. PMID: 17586664. PMCID: PMC1950982.


14. Quast C., Pruesse E., Yilmaz P. et al. The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools. Nucleic Acids Res. 2013; 41(Database issue): D590–6.


https://doi.org/10.1093/nar/gks1219. PMID: 23193283. PMCID: PMC3531112.


15. Love C.J., Gubert C., Kodikara S. et al. Microbiota DNA isolation, 16S rRNA amplicon sequencing, and bioinformatic analysis for bacterial microbiome profiling of rodent fecal samples. STAR Protoc. 2022; 3(4): 101772.


https://doi.org/10.1016/j.xpro.2022.101772. PMID: 36313541. PMCID: PMC9597187.


16. Wickham H. ggplot2: Elegant graphics for data analysis. J Stat Softw. 2010; 35(1): 65–88.


ISSN: 2197-5744 (electronic). https://doi.org/10.1007/978-3-319-24277-4.


17. Heinken A., Hertel J., Thiele I. Metabolic modelling reveals broad changes in gut microbial metabolism in inflammatory bowel disease patients with dysbiosis. NPJ Syst Biol Appl. 2021; 7(1): 19.


https://doi.org/10.1038/s41540-021-00178-6. PMID: 33958598. PMCID: PMC8102608.


18. Lupp C., Robertson M.L., Wickham M.E. et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe. 2007; 2(3): 204.


https://doi.org/10.1016/j.chom.2007.08.002. PMID: 18030708.


19. Ohkusa T., Nishikawa Y., Sato N. Gastrointestinal disorders and intestinal bacteria: Advances in research and applications in therapy. Front Med (Lausanne). 2023; 9: 935676.


https://doi.org/10.3389/fmed.2022.935676. PMID: 36825261. PMCID: PMC9941163.


20. Frost F., Storck L.J., Kacprowski T. et al. A structured weight loss program increases gut microbiota phylogenetic diversity and reduces levels of Collinsella in obese type 2 diabetics: A pilot study. PLoS One. 2019; 14(7): e0219489.


21. Ситкин С.И., Вахитов Т.Я., Демьянова Е.В. Микробиом, дисбиоз толстой кишки и воспалительные заболевания кишечника: когда функция важнее таксономии. Альманах клинической медицины. 2018; 46(5): 396–425. (Sitkin S.I., Vakhitov T.Ya., Demyanova E.V. Microbiome, gut dysbiosis and inflammatory bowel disease: That moment when the function is more important than taxonomy. Al’manakh klinicheskoy meditsiny = Almanac of Clinical Medicine. 2018; 46(5): 396–425 (In Russ.)). EDN: YNLTYL.


https://doi.org/10.18786/2072-0505-2018-46-5-396-425.


22. Карпунина Т.И., Галимзянова А.А., Карпунина Н.С., Годовалов А.П. Взаимодействие микробиоты кишечника с организмом хозяина в состоянии эубиоза и дисбиоза. Экспериментальная и клиническая гастроэнтерология. 2023; 214(6): 105–112. (Karpunina T.I., Galimzyanova A.A., Karpunina N.S., Godovalov A.P. “Host-gut microbiota” interactions in a case of eubiosis and dysbiosis. Eksperimentalnaya i klinicheskaya gastroenterologiya = Experimental and Clinical Gastroenterology. 2023; 214(6): 105–112 (In Russ.)).


https://doi.org/10.31146/1682-8658-ecg-214-6-105-112. EDN: JQXMYU.


23. Seo M., Heo J., Yoon J. et al. Methanobrevibacter attenuation via probiotic intervention reduces flatulence in adult human: A non-randomised paired-design clinical trial of efficacy. PLoS One. 2017; 12(9): e0184547.


https://doi.org/10.1371/journal.pone.0184547. PMID: 28937980. PMCID: PMC5609747.


24. Ghavami S.B., Rostami E., Sephay A.A. et al. Alterations of the human gut Methanobrevibacter smithii as a biomarker for inflammatory bowel diseases. Microb Pathog. 2018; 117: 285–89.


https://doi.org/10.1016/j.micpath.2018.01.029. PMID: 29477743.


25. Белоусова Е.А., Абдулганиева Д.И., Алексеева О.П. с соавт. Социально-демографическая характеристика, особенности течения и варианты лечения воспалительных заболеваний кишечника в России. Результаты двух многоцентровых исследований. Альманах клинической медицины. 2018; 46(5): 445–463. (Belousova E.A., Abdulganieva D.I., Alexeeva O.P. et al. Social and demographic characteristics, features of disease course and treatment options of inflammatory bowel disease in Russia: Results of two multicenter studies. Al’manakh klinicheskoy meditsiny = Almanac of Clinical Medicine. 2018; 46(5): 445–463 (In Russ.)).


https://doi.org/10.18786/20720505-2018-46-5-445-463. EDN: YNLTZB.


26. Zhang L., Chu J., Hao W. et al. Gut microbiota and type 2 diabetes mellitus: Association, mechanism, and translational applications. Mediators Inflamm. 2021; 2021: 5110276.


https://doi.org/10.1155/2021/5110276. PMID: 34447287. PMCID: PMC8384524.


27. Maskarinec G., Raquinio P., Kristal B.S. et al. The gut microbiome and type 2 diabetes status in the Multiethnic Cohort. PLoS One. 2021; 16(6): e0250855.


https://doi.org/10.1371/journal.pone.0250855. PMID: 34161346. PMCID: PMC8221508.


About the Autors


Svetlana N. Lagutina, MD, assistant at the Department of outpatient therapy, N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia. Address: 394036, Voronezh, 10 Studencheskaya St.
E-mail: svlagutina97@mail.ru
ORCID: https://orcid.org/0000-0003-3730-5265
Anna A. Pashkova, MD, Dr. Sci. (Medicine), professor, head of the Department of polyclinic therapy, N.N. Burdenko Voronezh State Medical University of the Ministry of Healthcare of Russia. Address: 394036, Voronezh, 10 Studencheskaya St.
E-mail: zuikova-therapia@vrngmu.ru
ORCID: https://orcid.org/0000-0002-5378-4959
Vasilisa V. Dudurich, MD, researcher at the Mega-faculty “Science about life” of ITMO University, head of the Department of metagenomic research of the Laboratory of genetics Serbalab LLC. Address: 199106, Saint Petersburg, 90 Bolshoi Avenue of Vasilyevsky Island.
E-mail: vasilisadudurich@yandex.ru
ORCID: https://orcid.org/0000-0002-6271-5218
Lavrentiy G. Danilov, MD, head of the Department “Bioinformatics” of the Laboratory of genetics Serbalab LLC. Address: 199106, Saint Petersburg, 90 Bolshoi Avenue of Vasilyevsky Island.
E-mail: lavrentydanilov@gmail.com
ORCID: https://orcid.org/0000-0002-4479-3095
Ekaterina D. Ermachenko, MD, head of the development group of the Laboratory of PCR, senior biotechnologist at the Laboratory of genetics Serbalab LLC. Address: 199106, Saint Petersburg, 90 Bolshoi Avenue of Vasilyevsky Island.
E-mail: ermachenkoed@mail.ru
ORCID: https://orcid.org/0000-0003-1694-84872


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