Profile of subpopulation composition of regulatory T lymphocytes and intestinal microbiota in patients with irritable bowel syndrome
https://doi.org/10.15789/1563-0625-POS-1905
Abstract
The following specificcharacteristics of the composition of intestinal microbiota in patients with irritable bowel syndrome (IBS) were identified using a metagenomic analysis (16 S rRNA): 1) an increase in the representation of Actinobacteria, including Bifidobacterium spp., Firmicutes, including representatives of Streptococcaceae (Streptococcus), Lachnosperaceae (Dorea), Veillonellaceae (Dialister), Proteobacteria (Enterobacteriaceae and Desulfovibrionaceae families); 2) a decrease in the population of Bacteroidetes, including representatives of the families Prevotellacea (Prevotella spp.), Bacteroidaceae (Bacteroides spp.). Firmicutes belonging to the families Clostridiaceae and Ruminococcaceae (Fecalibacterium spp.).
Flow cytometry in the study of the subpopulation composition of T regulatory (Treg) lymphocytes in patients with IBS revealed an increase in the number of CD45R0+CD62L+ central memory cells (CM), which can regulate the processes of maturation and differentiation of lymphocytes in lymphoid tissue. A decrease in the expression of exonucleases CD39 and CD73 was detected, which can have a significant effect on their activity. A reduction in effector memory cells (EM) Treg was observed.
Changes in the expression level of exonucleases CD39 and CD73 were inversely correlated with the content of Proteobacteria and the representation of the genera Bifidobacterium spp. and Faecalibacterium spp. The content of СЫ Treg was directly correlated with the content of Dorea spp.
The results may be indicative of impairment in the processes of Treg differentiation, which are closely related to changes in key components of intestinal microbiocenosis in IBS.
Keywords
About the Authors
E. I. ErmolenkoRussian Federation
PhD, MD (Medicine), Associate Professor, Head, Laboratory of Biomedical Microecology, Department of Molecular Microbiology, IEM; Professor, Department of Physiology, St.PSU.
St. Petersburg
Competing Interests: not
I. V. Kudryavtsev
Russian Federation
PhD (Biology), Senior Research Associate, Department of Immunology, IEM; Associate Professor, Department of Immunology, First St. Petersburg State I. Pavlov MU.
St. PetersburgCompeting Interests: not
O. I. Solovyova
Russian Federation
PhD (Medicine), Associate Professor, Department of Internal Diseases, Clinical Pharmacology and Nephrology, North-Western State I. Mechnikov MU.
St. PetersburgCompeting Interests: not
A. B. Karaseva
Russian Federation
Research Associate, Department of Molecular Microbiology.
St. PetersburgCompeting Interests: not
A. N. Tsapieva
Russian Federation
Research Associate, Department of Molecular Microbiology.
St. Petersburg
Competing Interests: not
Yu. D. Kondratenko
Russian Federation
Software Engineer, Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St.PSU.
St. Petersburg, Russian Federation
Competing Interests: not
M. P. Kotyleva
Russian Federation
Research Associate, Department of Molecular Microbiology.
St. PetersburgCompeting Interests: not
M. K. Serebryakova
Russian Federation
Research Associate, Department of Immunology.
St. PetersburgCompeting Interests: not
I. A. Shumikhina
Russian Federation
Senior Laboratory Assistant, Department of Internal Diseases, Clinical Pharmacology and Nephrology, N-WS I. Mechnikov MU.
St. PetersburgCompeting Interests: not
A. N. Suvorov
Russian Federation
PhD, MD (Medicine), Сorresponding Member, Russian Academy of Sciences, Head, Department of Molecular Microbiology, IEM; Head, Department of Fundamental Medicine and Medical Technologies, St.PSU.
St. PetersburgCompeting Interests: not
References
1. Akehurst R.L., Brazier J.E., Mathers N., O’Keefe C., Kaltenthaler E., Morgan A., Platts M., Walters S.J. Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting. Pharmacoeconomics, 2002, Vol. 20, no. 7, pp. 455-462.
2. Averina O.V., Ermolenko E.I., Ratushniy A.Yu., Tarasova E.A., Borschev Yu.Yu., Leontieva G.F., Kramskaya T.A., Kotyleva M.P., Danilenko V.N., Suvorov A.N. Effect of probiotics on the production of cytokines in the systems in vitro. Medical Immunology (Russia), 2015, Vol. 17, no. 5, pp. 443-454. doi: 10.15789/1563-0625-2015-5-443-454.
3. Belmer S.V. Immunological aspects of irritable bowel syndrome. Physician, 2016, no. 8, pp. 14-18.
4. Chong P.P., Chin V.K., Looi C.Y., Wong W.F., Madhavan P, Yong V.C. The Microbiome and irritable bowel syndrome - a review on the pathophysiology, current research and future therapy. Front. Microbiol., 2019, Vol. 10, 1136. doi: 10.3389/fmicb.2019.01136.
5. Drossman D.A., Hasler W.L. Rome IV - Functional GI disorders: disorders of gut-brain interaction. Gastroenterology, 2016, Vol. 150, no. 6, pp. 1257-1261.
6. Eeckhaut V, Machiels K., Perrier C., Romero C., Maes S., Flahou B., Steppe M., Haesebrouck F., Sas B., Ducatelle R., Vermeire S., van Immerseel F. Butyricicoccus pullicaecorum in inflammatory bowel disease. Gut, 2013, Vol. 62, no. 12, pp. 1745-1752.
7. Forshammar J., Isaksson S., Strid H., Stotzer P.O., Sjbvall H., Simren M., Ohman L. A pilot study of colonic B cell pattern in irritable bowel syndrome. Scand. J. Gastroenterol., 2008, Vol. 43, no. 12, pp. 1461-1466.
8. Golovkin A.S., Asadullina I.A., Kudryavtsev I.V. Purinergic regulation of basic physiological and pathological processes. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 4, pp. 463-476. doi: 10.15789/1563-0625-2018-4-463-476.
9. Gonsalkorale W.M., Perrey C., Pravica V, Whorwell P.J., Hutchinson I.V. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut, 2003, Vol. 52, no. 1, pp. 91-93.
10. Grant C.R., Liberal R., Mieli-Vergani G., Vergani D., Longhi M.S. Regulatory T-cells in autoimmune diseases: challenges, controversies and - yet - unanswered questions. Autoimmun. Rev., 2015, Vol. 14, pp. 105-116.
11. Hod K., Ringel-Kulka T., Martin C.F., Maharshak N., Ringel Y. High-sensitive C-reactive protein as a marker for inflammation in irritable bowel syndrome. J. Clin. Gastroenterol., 2016, Vol. 50, no. 3, pp. 227-232.
12. Holmen N., Isaksson S., Simren M., Sjbvall H., Ohman L. CD4+CD25+ regulatory T cells in irritable bowel syndrome patients. Neurogastroenterol. Motil., 2007, Vol. 19, no. 2, pp. 119-125.
13. Ivashkin V.T., Maev I.V., Sheptulin A.A., Trukhmanov A.S., Alexeyeva O.P., Baranskaya E.K., Ivashkin K.V., Kalinin A.V., Korochanskaya N.V., Kucherya Y.A., Lapina T.L., Plotnikova E.Y., Poluektova E.A., Simanenkov V.I., Partova, A.V. Tkachev O.A., Shifrin O.S., Tarasova L.V., Khlynov I.B. Resolution of Advisory council “How to improve treatment results functional dyspepsia and irritable bowel syndrome”? Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2016, no. 2, pp. 101-104.
14. Kassinen A., Krogius-Kurikka L., Makivuokko H., Rinttila T., Paulin L., Corander J., Malinen E., Apajalahti J., Palva A. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology, 2007, Vol. 133, no. 1, pp. 24-33.
15. Kim H.Y., Kim T.S., Kim B.H. Degradation of organic sulfur compounds and the reduction of dibenzothiophene to biphenyl and hydrogen sulfide by Desulfovibrio desulfuricans M6. Biotechnol. Let., 1990, Vol. 12, no. 10, pp. 761-764.
16. Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolian Areg A. Standardized technology “Research of subpopulation composition of peripheral blood lymphocytes using pro-tread cytofluorimeters-analyzers” (Project). Medical Immunology (Russia), 2012, Vol. 14, no. 3, pp. 255-268. doi: 10.15789/1563-0625-2012-3-255-268.
17. Kindt S., van Oudenhove L., Broekaert D., Kasran A., Ceuppens J.L., Bossuyt X., Fischler B., Tack J. Immune dysfunction in patients with functional gastrointestinal disorders. Neurogastroenterol. Motil., 2009, Vol. 21, no. 4, pp. 389-398.
18. Kudryavtsev I.V., Ermolenko E.I., Solovyova O.I., Serebryakova M.K., Shumikhina I.A., Suvorov A.N. Subpopulation composition oft-lymphocytes in irritable bowel syndrome. Experimental and Clinical Gastroenterology (Russia), 2019, no. 5, pp. 22-28.
19. Lovell R.M., Ford A.C. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin. Gastroenterol. Hepatol., 2012, Vol. 10, no. 7, pp. 712-721.
20. Lucas K. Role of the Toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol. Neurobiol., 2013, Vol. 48, pp. 190-204.
21. Mazmanian S.K. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 2008, Vol. 453, pp. 620-625.
22. Miquel S., Martin R., Rossi O., Bermudez-Humaran L., Chatel J., Sokol H., Thomas M., Wells J., Langella P Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol., 2013, Vol. 16, no. 3, pp. 255-261.
23. Nasser Y., Petes C., Simmers C., Basso L., Altier C., Gee K., Vanner S.J.. Activation of peripheral blood CD4+ T-cells in IBS is not associated with gastrointestinal or psychological symptoms. Sci. Rep., 2019, Vol. 9, no. 1, 3710. doi: 10.1038/s41598-019-40124-5.
24. Nurkhametova D., Kudryavtsev I., Khayrutdinova O., Serebryakova M., Altunbaev R., Malm T., Giniatullin R. Purinergic profiling of regulatory T-cells in patients with episodic migraine. Front. Cell. Neurosci., 2018, Vol. 12, 326. doi: 10.3389/fncel.2018.00326.
25. Pozuelo M., Panda S., Santiago A., Mendez S., Accarino A., Santos J., Guarner F., Azpiroz F., Manichanh C. Reduction of butyrate-and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci. Rep., 2015, Vol. 5, 12693. doi: 10.1038/srep12693.
26. Rajilic-Stojanovic M., Biagi E., Heilig H.G., Kajander K., Kekkonen R.A., Tims S., de Vos W.M. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology, 2011, Vol. 141, no. 5, pp. 1792-1801.
27. Rigsbee L., Agans R., Shankar V., Kenche H., Khamis H.J., Michail S., Paliy O. Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome. Am. J. Gastroenterol., 2012, Vol. 107, no. 11, pp. 1740-1751.
28. Rissiek A., Baumann I., Cuapio A., Mautner A., Kolster M., Arck P.C., Dodge-Khatami A., Mittrucker H.W., Koch-Nolte F., Haag F., Tolosa E. The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation. J. Autoimmun., 2015, Vol. 58, pp. 12-20.
29. Rodes L., Khan A., Paul A., Coussa-Charley M., Marinescu D., Tomaro-Duchesneau C., Shao W., Kahouli I., Prakash S. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J. Microbiol. Biotechnol., 2013, Vol. 23, pp. 518-526.
30. Sakaguchi S., Miyara M., Costantino C.M., Hafler D.A. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol., 2010, Vol. 10, pp. 490-500.
31. Schirmer M., Smeekens S.P., Vlamakis H., Jaeger M., Oosting M., Franzosa E.A., Ter Horst R., Jansen T., Jacobs L., Bonder M.J., Kurilshikov A., Fu J., Joosten L.A.B., Zhernakova A., Huttenhower C., Wijmenga C., Netea M.G., Xavier R.J. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell, 2016, Vol. 167, no. 4, pp. 1125-1136.
32. Sitkin S.I., Tkachenko E.I., Vakhitov T.Ya. Metabolic bowel dysbiosis and its biomarkers. Experimental and Clinical Gastroenterology, 2015, no. 12, pp. 6-29.
33. Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly-Y M., Glickman J.N., Garrett W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013, Vol. 341, pp. 569-573.
34. Solovyova O.I., Simanenkov V.I., Suvorov A.N., Ermolenko E.I., Shumihina I.A., Svirido D.A. Use of probiotics and pre-probiotics in the treatment ofirritable bowel syndrome. Experimental and Clinical Gastroenterology (Russia), 2017, no. 7, pp. 115-120.
35. Suzuki D., Ueki A., Amaishi A., Ueki K. Desulfovibrio portus sp. nov., a novel sulfate-reducing bacterium in the class Deltaproteobacteria isolated from an estuarine sediment. J. Gen. Appl. Microbiol., 2009, Vol. 55, no. 2, pp. 125-133.
36. Tana C., Umesaki Y., Imaoka A., Handa T., Kanazawa M., Fukudo S. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol. Motil., 2010, Vol. 22, no. 5, pp. 512-519.
37. Tap J., Derrien M., Tbrnblom H., Brazeilles R., Cools-Portier S., Dore J., Stbrsrud S., le Neve B., Ohman L., Simren M. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology, 2017, Vol. 152, pp. 111-123.
38. Taras D., Simmering R., Collins M.D., Lawson P.A., Blaut M. Reclassification of Eubacterium formicigenerans Holdeman and Moore 1974 as Dorea formicigenerans gen. nov., comb. nov., and description of Dorea longicatena sp. nov., isolated from human faeces. Int. J. Syst. Evol. Microbiol., 2002, Vol. 52, Pt 2, pp. 423-428.
Supplementary files
![]() |
1. метаданные | |
Subject | ||
Type | Other | |
Download
(81KB)
|
Indexing metadata ▾ |
![]() |
2. литература | |
Subject | ||
Type | Other | |
Download
(49KB)
|
Indexing metadata ▾ |
![]() |
3. литература таблица | |
Subject | ||
Type | Other | |
Download
(266KB)
|
Indexing metadata ▾ |
![]() |
4. литература таблица | |
Subject | ||
Type | Other | |
Download
(266KB)
|
Indexing metadata ▾ |
![]() |
5. рисунок 1 | |
Subject | ||
Type | Other | |
Download
(896KB)
|
Indexing metadata ▾ |
![]() |
6. Рисунок 2 | |
Subject | ||
Type | Other | |
Download
(128KB)
|
Indexing metadata ▾ |
![]() |
7. Рисунок 3 | |
Subject | ||
Type | Other | |
Download
(178KB)
|
Indexing metadata ▾ |
![]() |
8. Рисунок 3 | |
Subject | ||
Type | Other | |
Download
(178KB)
|
Indexing metadata ▾ |
![]() |
9. Рисунок 4 | |
Subject | ||
Type | Other | |
Download
(B)
|
Indexing metadata ▾ |
![]() |
10. Рисунок 5 | |
Subject | ||
Type | Other | |
Download
(23KB)
|
Indexing metadata ▾ |
![]() |
11. Рисунок 6 | |
Subject | ||
Type | Other | |
Download
(141KB)
|
Indexing metadata ▾ |
![]() |
12. Рисунок 7 | |
Subject | ||
Type | Other | |
Download
(20KB)
|
Indexing metadata ▾ |
![]() |
13. Рисунок 8. | |
Subject | ||
Type | Other | |
Download
(20KB)
|
Indexing metadata ▾ |
![]() |
14. Подписи к рисункам | |
Subject | ||
Type | Other | |
Download
(79KB)
|
Indexing metadata ▾ |
![]() |
15. метданные | |
Subject | ||
Type | Other | |
Download
(81KB)
|
Indexing metadata ▾ |
![]() |
16. Титульный лист | |
Subject | ||
Type | Other | |
Download
(72KB)
|
Indexing metadata ▾ |
![]() |
17. таблица 1 | |
Subject | ||
Type | Other | |
Download
(53KB)
|
Indexing metadata ▾ |
![]() |
18. таблица 2. | |
Subject | ||
Type | Other | |
Download
(101KB)
|
Indexing metadata ▾ |
![]() |
19. Таблица 3. | |
Subject | ||
Type | Other | |
Download
(62KB)
|
Indexing metadata ▾ |
Review
For citations:
Ermolenko E.I., Kudryavtsev I.V., Solovyova O.I., Karaseva A.B., Tsapieva A.N., Kondratenko Yu.D., Kotyleva M.P., Serebryakova M.K., Shumikhina I.A., Suvorov A.N. Profile of subpopulation composition of regulatory T lymphocytes and intestinal microbiota in patients with irritable bowel syndrome. Medical Immunology (Russia). 2020;22(2):335-346. https://doi.org/10.15789/1563-0625-POS-1905