Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology135810.36233/0372-9311-270REVIEWSОБЗОРЫResearch ArticleRole of intestinal microbiota in regulation of immune reactions of gut-associated lymphoid tissue under stress and following the modulation of its composition by antibiotics and probiotics administrationРоль кишечной микробиоты в регуляции иммунных реакций в иммунной системе кишечника в условиях стресса и при модуляции её состава путём введения антибиотиков и пробиотиковhttps://orcid.org/0000-0001-7729-1465TopolInna A.ТополИнна Александровна
Russian Federation

Cand. Sci. (Biol.), Associate Professor, Department of biomedical disciplines

к.б.н., доцент каф. медико-биологических дисциплин

innatopol08@gmail.comhttps://orcid.org/0000-0002-0228-3513PolyakovaIrina S.ПоляковаИрина Сергеевна
Russian Federation

Cand. Sci. (Biol.), Associate Professor, Department of biomedical disciplines

к.б.н., доцент кафедры медико-биологических дисциплин

innatopol08@gmail.comhttps://orcid.org/0000-0002-9511-6895ElykovaAnna V.ЕлыковаАнна Владимировна
Russian Federation

Cand. Sci. (Biol.), Associate Professor, Department of biomedical disciplines

к.б.н., доцент кафедры медико-биологических дисциплин

innatopol08@gmail.comBelgorod State National Research UniversityБелгородский государственный национальный исследовательский университет151220229967227331001202310012023Copyright ©; 2022, Topol I.A., Polyakova I.S., Elykova A.V.Copyright ©; 2022, Топол И.А., Полякова И.С., Елыкова А.В.2022Topol I.A., Polyakova I.S., Elykova A.V.Топол И.А., Полякова И.С., Елыкова А.В.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/1358

Over the past two decades, active study of the microbial ecosystem of the host organism gastrointestinal tract has led to the recognition of gut microbiome as a "key player" that carries a significant immune pressure and is responsible both for the course of physiological processes and for the development of pathological conditions in humans and animals. A vast number of bacteria living in the human gastrointestinal tract are considered as an “organ functioning in dialogue” in formation of immunological tolerance, the regulation of normal functional activity of the immune system and maintaining the intestinal mucosa homeostasis. However, disturbances in interaction between these physiological systems is closely related to the pathogenesis of different immune-mediated diseases. In turn, in a large number of works chronic social stress, along with the use of antibiotics, pre- and probiotics, is recognized as one of the leading factors modulating in the microbiota of the gastrointestinal tract. This review focuses on the role of the gut microbiome in the regulation of immune responses of GALT under stress and modulation of its composition by antibiotics and probiotics administration.

Интенсивное изучение в течение последних двух десятилетий микробной экосистемы желудочно-кишечного тракта (ЖКТ) организма хозяина привело к тому, что кишечный микробиом был признан фундаментальным «игроком», который несет огромную иммунную нагрузку и отвечает как за течение физиологических процессов, так и за развитие патологических состояний человека и животных. Огромное количество бактерий, обитающих в ЖКТ человека, рассматривается как «функционирующий в диалоге орган» в формировании иммунологической толерантности, регуляции нормальной функциональной активности иммунной системы и поддержании гомеостаза слизистой оболочки кишечника. Нарушение взаимодействия между этими физиологическими системами тесно связано с патогенезом различных иммуноопосредованных заболеваний. В свою очередь, всё чаще хронический социальный стресс, наряду с приёмом антибиотиков, пре- и пробиотиков, признаётся одним из ведущих факторов, модулирующих состав микроорганизмов, обитающих в ЖКТ. Настоящий обзор посвящён изучению роли кишечного микробиома в регуляции иммунных реакций кишечно-ассоциированной лимфоидной ткани в условиях стресса и при модуляции её состава путём введения антибиотиков и пробиотиков.

reviewchronic stressgut microbiotaantibioticsprobioticsобзорхронический стресскишечная микробиотаантибиотикипробиотикиMackos A.R., Maltz R., Bailey M.T. The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation. Horm. Behav. 2017; 88: 70–8. https://doi.org/10.1016/j.yhbeh.2016.10.006Mackos A.R., Varaljay V.A., Maltz R., Gur T.L., Bailey M.T. Role of the intestinal microbiota in host responses to stressor exposure. Int. Rev. Neurobiol. 2016; 131: 1–19. https://doi.org/10.1016/bs.irn.2016.08.002Powell N. Psychosocial stress and inflammation in cancer. Brain. Behav. Immun. 2013; 30(Suppl.): 41–7. https://doi.org/10.1016/j.bbi.2012.06.015Delévaux I. Stress and auto-immunity. Rev. Med. Interne. 2013; 34(8): 487–92. https://doi.org/10.1016/j.revmed.2012.10.366Wei L., Li Y., Tang W., Sun Q., Chen L., Wang X., et al. Chronic unpredictable mild stress in rats induces colonic inflammation. Front. Physiol. 2019; 10: 1228. https://doi.org/10.3389/fphys.2019.01228Nishida A., Inoue R., Inatomi O., Bamba S., Naito Y., Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin. J. Gastroenterol. 2018; 11(1): 1–10. https://doi.org/10.1007/s12328-017-0813-5Reber S.O., Peters S., Slattery D.A., Hofmann C., Schölmerich J., Neumann I.D., et al. Mucosal immunosuppression and epithelial barrier defects are key events in murine psychosocial stress-induced colitis. Brain Behav. Immun. 2011; 25(6): 1153–61. https://doi.org/10.1016/j.bbi.2011.03.004Aadra P.B., Matthew R.R., Scott J.B. The role of the microbiome in cancer development and therapy CA. Cancer J. Clin. 2017; 67(4): 326–44. https://doi.org/10.3322/caac.21398Zheng P., Wu J., Zhang H., Perry S.W., Yin B., Tan X., et al. The gut microbiome modulates gut-brain axis glycerophospholipid metabolism in a region-specific manner in a nonhuman primate model of depression. Mol. Psychiatry. 2020; 26(6): 2380–92. https://doi.org/10.1038/s41380-020-0744-2Bharwani A., Mian M.F., Foster J.A., Surette M.G., Bienenstock J., Forsythe P. Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology. 2016; 63: 217–27. https://doi.org/10.1016/j.psyneuen.2015.10.001Ding F., Wu J., Liu C., Bian Q., Qiu W., Ma Q., et al. Effect of Xiaoyaosan on colon morphology and intestinal permeability in rats with chronic unpredictable mild stress. Front. Pharmacol. 2020; 11: 1069. https://doi.org/10.3389/fphar.2020.01069González-Torres M.L., Dos Santos C.V. Uncontrollable chronic stress affects eating behavior in rats. Stress. 2019; 22(4): 501–8. https://doi.org/10.1080/10253890.2019.1596079Gur T.L., Bailey M.T. Effects of stress on commensal microbes and immune system activity. Adv. Exp. Med. Biol. 2016; 874: 289–300. https://doi.org/10.1007/978-3-319-20215-0_14Karl J.P., Hatch A.M., Arcidiacono S.M., Pearce S.C., Pantoja-Feliciano I.G., Doherty L.A., et al. Effects of psychological, environmental and physical stressors on the gut microbiota. Front. Microbiol. 2018; 9: 2013. https://doi.org/10.3389/fmicb.2018.02013Molina-Torres G., Rodriguez-Arrastia M., Roman P., Sanchez-Labraca N., Cardona D. Stress and the Gut Microbiota-Brain axis. Behav. Pharmacol. 2019; 30(2 and 3 Spec. Issue): 187–200. https://doi.org/10.1097/FBP.0000000000000478Salonen A., Lahti L., Salojärvi J., Holtrop G., Korpela K., Duncan S.H., et al. Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men. ISME J. 2014; 8(11): 2218–30. https://doi.org/10.1038/ismej.2014.63Jung C., Hugot J.P., Barreau F. Peyer’s patches: the immune sensors of the intestine. Int. J. Inflam. 2010; 2010: 823710. https://doi.org/10.4061/2010/823710Vitetta L., Coulson S., Linnane A.W., Butt H. The gastrointestinal microbiome and musculoskeletal diseases: a beneficial role for probiotics and prebiotics. Pathogens. 2013; 2(4): 606–26. https://doi.org/10.3390/pathogens2040606Kim M., Kim C.H. Regulation of humoral immunity by gut microbial products. Gut Microbes. 2017; 8(4): 392–9. https://doi.org/10.1080/19490976.2017.1299311Kim C.H. Immune regulation by microbiome metabolites. Immunology. 2018; 154(2): 220–9. https://doi.org/10.1111/imm.12930Zhao Q., Elson C.O. Adaptive immune education by gut microbiota antigens. Immunology. 2018; 154(1): 28–37. https://doi.org/10.1111/imm.12896Claes A.K., Zhou J.Y., Philpott D.J. NOD-like receptors: guardians of intestinal mucosal barriers. Physiology (Bethesda). 2015; 30(3): 241–50. https://doi.org/10.1152/physiol.00025.2014Sellge G., Kufer T.A. PRR-signaling pathways-learning from microbial tactics. Semin. Immunol. 2015; 27(2): 75–84. https://doi.org/10.1016/j.smim.2015.03.009Degen A.S., Kamyshnyy A.M. Expression of cytoplasmic NOD-2 and RIG-I receptors of innate immunity in intestine of rats in experimental diabetes mellitus. Rossiyskiy immunologicheskiy zhurnal. 2014; 8(3): 525–8. (in Russian)Деген А.С., Камышный А.М. Экспрессия цитоплазматических NOD-2 и RIG-I рецепторов врожденного иммунитета в кишечнике крыс при экспериментальном сахарном диабете. Российский иммунологический журнал. 2014; 8(3): 525–8.Shi N., Li N., Duan X., Niu H. Interaction between the gut microbiome and mucosal immune system. Mil. Med. Res. 2017; 4: 14. https://doi.org/10.1186/s40779-017-0122-9Zanin-Zhorov A., Cohen I.R. Signaling via TLR2 and TLR4 directly down-regulates T cell effector functions: the regulatory face of danger signals. Front. Immunol. 2013; 4: 211. https://doi.org/10.3389/fimmu.2013.00211Bailey M., Engler H., Powell N., Padgett D.A., Sheridan J.F. Repeated social defeat increases the bactericidal activity of splenic macrophages through a Toll-like receptor-dependent pathway. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007; 293(3): 1180–90. https://doi.org/10.1152/AJPREGU.00307.2007Bailey M., Dowd S., Galley J. Exposure to a social stress or alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav. Immun. 2011; 25: 397–407. https://doi.org/10.1016/j.bbi.2010.10.023Kamdar K., Nguyen V., DePaolo R.W. Toll-like receptor signaling and regulation of intestinal immunity. Virulence. 2013; 4(3): 207–12. https://doi.org/10.4161/viru.23354Liu G., Zhang L., Zhao Y. Modulation of immune responses through direct activation of Toll-like receptors to T cells. Clin. Exp. Immunol. 2010; 160(2): 168–75. https://doi.org/10.1111/j.1365-2249.2010.04091.xYue Y., Chen Y., Liu H., Xu L., Zhou X., Ming H., et al. Shugan Hewei decoction alleviates cecum mucosal injury and improves depressive- and anxiety-like behaviors in chronic stress model rats by regulating cecal microbiota and inhibiting NLRP3 inflammasome. Front. Pharmacol. 2021; 12: 766474. https://doi.org/10.3389/fphar.2021.766474Ivanov I.I., Atarashi K., Manel N., Brodie E.L., Shima T., Karaoz U., et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009; 139(3): 485–98. https://doi.org/10.1016/j.cell.2009.09.033Buchta C.M., Bishop G.A. Toll-like receptors and B cells: functions and mechanisms. Immunol. Res. 2014; 59(1-3): 12–22. https://doi.org/10.1007/s12026-014-8523-2Bailey M., Kierstein S., Sharma S., Spaits M., Kinsey S.G., Tliba O., et al. Social stress enhances allergen-induced airway inflammation in mice and inhibits corticosteroid responsiveness of cytokine production. J. Immunol. 2009; 182(12): 7888–96. https://doi.org/10.4049/jimmunol.0990062Powell N.D., Bailey M.T., Mays J.W., Stiner-Jones L.M., Hanke M.L., Padgett D.A., et al. Repeated social defeat activates dendritic cells and enhances Toll-like receptor dependent cytokine secretion. Brain Behav. Immun. 2009; 23(2): 225–31. https://doi.org/10.1016/j.bbi.2008.09.010Bailey M.T., Dowd S.E., Parry N.M., Galley J.D., Schauer D.B., Lyte M. Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium. Infect. Immun. 2010; 78(4): 1509–19. https://doi.org/10.1128/IAI.00862-09Bartolomucci A. Social stress, immune functions and disease in rodents. Front. Neuroendocrinol. 2007; 28(1): 28–49. https://doi.org/10.1016/j.yfrne.2007.02.001Whiteley M., Diggle S.P., Greenberg E.P. Progress in and promise of bacterial quorum sensing research. Nature. 2017; 551(7680): 313–20. https://doi.org/10.1038/nature24624Schwab M., Bergonzi C., Sakkos J., Staley C., Zhang Q., Sadowsky M.J., et al. Corrigendum: signal disruption leads to changes in bacterial community population. Front. Microbiol. 2021; 12: 691552. https://doi.org/10.3389/fmicb.2021.691552Sperandio V., Torres A., Jarvis B., Kaper J.B. Bacteria-host communication: the language of hormones. Proc. Natl Acad. Sci. USA. 2003; 100(15): 8951–6. https://doi.org/10.1073/pnas.1537100100Wahlstrom A., Sayin S.I., Marschall H., Backhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016; 24(1): 41–50. https://doi.org/10.1016/j.cmet.2016.05.005Gareau M.G., Sherman P.M., Walker W.A. Рrobiotics and the gut microbiota in intestinal health and disease. Nat. Rev. Gastroenterol. Hepatol. 2010; 7(9): 503–14. https://doi.org/10.1038/nrgastro.2010.117Bosco N., Noti M. The aging gut microbiome and its impact on host immunity. Genes Immun. 2021; 22(5-6): 289–303. https://doi.org/10.1038/s41435-021-00126-8Francino M.P., Moya A. Effects of antibiotic use on the microbiota of the gut and associated alterations of immunity and metabolism. EMJ Gastroenterol. 2013; (1): 74–80. https://doi.org/10.3389/fmicb.2015.01543Robinson C., Young V. Antibiotic administration alters the community structure of the gastrointestinal microbiota. Gut Microbes. 2010; (1): 279–84. https://doi.org/10.4161/gmic.1.4.12614Willing B., Russell S., Finlay B. Shifting the balance: antibiotic effects on host — microbiota mutualism. Nat. Rev. Microbiol. 2011; 9(4): 233–43. https://doi.org/10.1038/nrmicro2536Sandra R.S., González Núñez L., García Del Barco Herrera D., Santos Febles E., Maza Ares D., Millares López R., et al. Role of epidermal growth factor and growth hormone-releasing peptide-6 in acceleration of renal tissue repair after kanamycin overdosing in rats. Iran J. Kidney. Dis. 2014; 8(5): 382–8.Tahoun A., Mahajan S., Paxton E., Malterer G., Donaldson D.S., Wang D., et al. Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion. Cell Host Microbe. 2012; 12(5): 645–56. https://doi.org/10.1016/j.chom.2012.10.009Zelante T., Iannitti R.G., Cunha C., De Luca A., Giovannini G., Pieraccini G., et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013; 39(2): 372–85. https://doi.org/10.1016/j.immuni.2013.08.003Wu W., Sun M., Chen F., Cao A.T., Liu H., Zhao Y., et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota, which is mediated by GPR43. Mucosal. Immunol. 2017; 10(4): 946–56. https://doi.org/10.1038/mi.2016.114Park J., Kim M., Kang S.G., Jannasch A.H., Cooper B., Patterson J., et al. Short chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTORS6K pathway. Mucosal. Immunol. 2015; 8(1): 80–93. https://doi.org/10.1038/mi.2014.44Kazantseva A.V., Davydova Y.D., Enikeeva R.F., Valinurov R.G., Gareeva A.E., Khusnutdinova N.N., et al. The association study of polymorphic variants of hypothalamic-pituitary-adrenal system genes (AVPR1B, OXTR) and aggressive behavior manifestation: a focus on social environment. Res. Results Biomed. 2021; 7(3): 232–44. https://doi.org/10.18413/2658-6533-2021-7-3-0-3Shi L.Z., Wang R., Huang G., Vogel P., Neale G., Green D.R., et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 2011; 208(7): 1367–76. https://doi.org/10.1084/jem.20110278Chang P.V., Hao L., Offermanns S., Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA. 2014; 111(6): 2247–52. https://doi.org/10.1073/pnas.1322269111Singh N., Gurav A., Sivaprakasam S., Brady E., Padia R., Shi H., et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014; 40(1): 128–39. https://doi.org/10.1016/j.immuni.2013.12.007Lee E.Y., Lee Z.H., Song Y.W. CXCL10 and autoimmune diseases. Autoimmun. Rev. 2009; 8(5): 379–83. https://doi.org/10.1016/j.autrev.2008.12.002Avdeeva A.S. IFN-γ-induced protein 10 (IP-10) in rheumatoid arthritis: literature review and the authors own data. Nauchno-prakticheskaya revmatologiya. 2017; 55(6): 655–61. https://doi.org/10.14412/1995-4484-2017-655-661 (in Russian)Авдеева А.С. ИФН γ-индуцируемый белок 10 (IP-10) при ревматоидном артрите: обзор литературы и собственные данные. Научно-практическая ревматология. 2017; 55(6): 655–61. https://doi.org/10.14412/1995-4484-2017-655-661Round J.L., Mazmanian S.K. Inducible Foxp3+regulatory T-cell development by a commensal bacterium of the intestinal microbiota. PNAS. 2010; 107(27): 12204–9. https://doi.org/10.1073/pnas.0909122107Shida K., Nanno M., Nagata S. Flexible cytokine production by macrophages and T cells in response to probiotic bacteria: a possible mechanism by which probiotics exert multifunctional immune regulatory activities. Gut Microbes. 2011; 2(2): 109–14. https://doi.org/10.4161/gmic.2.2.15661Verma R., Lee C., Jeun E., Yi J., Kim K.S., Ghosh A., et al. Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3(+) regulatory T cells. Sci. Immunol. 2018; 3(28): eaat6975. https://doi.org/10.1126/sciimmunol.aat6975Ghadimi D., Helwig U., Schrezenmeir J., Heller K.J., de Vrese M. Epigenetic imprinting by commensal probiotics inhibits the IL-23/IL-17 axis in an in vitro model of the intestinal mucosal immune system. J. Leukocyte Biol. 2012; 92(4): 895–911. https://doi.org/10.1189/jlb.0611286Chen L., Zou Y., Peng J., Lu F., Yin Y., Li F., et al. Lactobacillus acidophilus suppresses colitis-associated activation of the IL-23/Th17 axis. J. Immunol. Res. 2015; 2015: 909514. https://doi.org/10.1155/2015/909514Trabelsi I., Ktari N., Ben Slima S., Hamden K., Ben Salah R. Effect of the probiotic strain Lactobacillus plantarum TN8 on trinitrobenzenesulfonic acid induced colitis in rats. J. Anim. Physiol. Anim. Nutr. (Berl.). 2017; 101(2): 311–19. https://doi.org/10.1111 / jpn.12536Azad A.K., Sarker M., Li T., Yin J. Probiotic species in the modulation of gut microbiota: an overview. Biomed. Res. Int. 2018; 2018: 9478630. https://doi.org/10.1155/2018/9478630Abdollahi-Roodsaz S., Joosten L.A., Koenders M.I., Devesa I., Roelofs M.F., Radstake T.R., et al. Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J. Clin. Invest. 2008; 118(1): 205–16. https://doi.org/10.1172/JCI32639Chiba Y., Shida K., Nagata S. Well-controlled pro-inflammatory cytokine responses of Peyer’s patch cells to probiotic Lactobacillus casei. Immunol. 2010; 130(3): 352–62. https://doi.org/10.1111/j.1365-2567.2009.03204.xLiu Y., Fatheree N., Mangalat N. Lactobacillus reuteri strains reduce incidence and severity of experimental necrotizing enterocolitis via modulation of TLR4 and NF-κB signaling in the intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 2012; 15: 608–17. https://doi.org/10.1152/ajpgi.00266.2011Zarrati M., Shidfar F., Nourijelyani K. Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 modulate gene expression of subset specific transcription factors and cytokines in peripheral blood mononuclear cells of obese and overweight people. Biofactors. 2013; 39(6): 633–43. https://doi.org/10.1002/biof.1128Shimazu T., Villena J., Tohno M., Fujie H., Hosoya S., Shimosato T., et al. Immunobiotic Lactobacillus jensenii elicits anti-inflammatory activity in porcine intestinal epithelial cells by modulating negative regulators of the Toll-like receptor signaling pathway. Infect. Immun. 2012; 80(1): 276–88. https://doi.org/10.1128/IAI.05729-11