Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House11375010.29296/24999490-2022-03-02ArticlesСтатьиReview ArticleThe role of the intestinal microbiota in the pathogenesis of bronchial asthmaРоль микробиоты кишечника в патогенезе бронхиальной астмыPotskherashviliNino DimitrovnaПоцхверашвилиНино Димитровна

PhD, Assistant Prof., Departament of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology

кандидат медицинских наук, ассистент кафедры пропедевтики внутренних болезней, гастроэнтерологии и гепатологии лечебного факультета

nino.med@mail.ruZolnikovaOxana YurievnaЗольниковаОксана Юрьевна

Dr. Sci. (Med.), Professor, Departament of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology

доктор медицинских наук, профессор кафедры пропедевтики внутренних болезней, гастроэнтерологии и гепатологии лечебного факультета

ks.med@mail.ruIvashkinVladimir TrofimovichИвашкинВладимир Трофимович

Dr. Sci. (Med.), RAS Academician, Professor, Departament Head, Departament of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology

доктор медицинских наук, профессор, академик РАН, заведующий кафедрой пропедевтики внутренних болезней, гастроэнтерологии и гепатологии лечебного факультета

kont07@yandex.ruSechenov First Moscow State University (Sechenov University)ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» (Сеченовский Университет) Министерства здравоохранения Российской Федерации15032022203VOL 20, NO3 (2022)ТОМ 20, №3 (2022)111918112022Copyright ©; 2022, Russkiy Vrach Publishing HouseCopyright ©; 2022, ИД "Русский врач"2022Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/113750

It is currently being discussed that the microbiota of the gastrointestinal tract and its metabolites affect the course of bronchial asthma (BA). The purpose to summarize the available data on the role of the intestinal microbiota in the pathogenesis of ВА. Material and methods. A analysis of the main foreign and domestic sources on PubMed / Medline, RSCI / elibrary databases over the last 25years has been carried out. Results. In the course of the analysis of published works, the key links in the pathogenesis of ВА and changes arising from disturbance of intestinal microbiota composition (hygienic hypothesis, early prescription of antibacterial drugs) were compared. The results of studies on the role of bacterial overgrowth syndrome in the small intestine are analyzed. The results of studies where microbiota correction by prescribing probiotics and prebiotics resulted in positive effects on the course and prognosis in ВА are presented. Conclusion. A lot of data has been accumulated confirming the significant pathogenetic role of the microbiota. The positive effects of pro-and prebiotics both on the microbial composition of the intestine and on the course and prognosis in ВА allow us to consider the microbiome as a marker and a possible target in ВА therapy. All of the above dictates the need for further research in this area.

Введение. Микробиота желудочно-кишечного тракта и ее метаболиты влияют на развитие бронхиальной астмы (БА). Цель. Обобщить имеющиеся данные о роли микробиоты кишечника в патогенезе БА. Материал и методы. Проведен анализ основных зарубежных и отечественных источников по базам данных PubMed/ Medline, РИНЦ/elibrary за последние 25лет. Результаты. В ходе анализа опубликованных работ сопоставлены ключевые звенья патогенеза БА и изменения, возникающие при нарушении состава микробиоты кишечника (гигиеническая гипотеза, раннее назначение антибактериальных препаратов). Анализируются результаты исследований, посвященных роли синдрома избыточного бактериального роста в тонкой кишке. Приведены результаты исследований положительных эффектов коррекции микробиоты путем назначения пробиотиков и пребиотиков на течение и прогноз при БА. Заключение: Накоплено много данных, подтверждающих значимую патегенетическую роль микробиоты. Положительные эффекты про- и пребиотиков как на микробный состав кишки, так и на течение и прогноз при БА позволяют рассматривать микробиом как маркер и возможную мишень в терапии БА, что диктует необходимость проведения дальнейших исследований в данной области.

intestinal microbiotabronchial asthmaprobioticscytokinesмикробиота кишечникабронхиальная астмапробиотикицитокиныThursby E., Nathalie J.Introduction to the human gut microbiota. Biochemical J. 2017; 474: 1823-36. https://doi.org/10.1042/BCJ20160510Aagaard K., Riehle K., Ma J., Segata N., Mistretta T.-A., Coarfa C. Ametagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS ONE. 2012; 7: 36-46. https://doi.org/10.1371/journal.pone.0036466Backhed F, Roswall J., Peng Y, Feng Q., Jia H., Kovatcheva-Datchary P. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015; 17: 5. https://doi.org/10.1016/j.chom.2015.04.004Jakobsson H.E., Abrahamsson T.R., Jenmalm M.C., Harris K., Quince C., Jernberg C. Decreased gut microbiota diversity, delayed Bacteroidetescolonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2012; 63: 559-66. https://doi.org/10.1136/gutjnl-2012-303249Avershina E., Storr0 O., 0ien T., Johnsen R., Pope P., Rudi K. Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children. FEMS Microbiol. Ecol. 2014; 87: 280-90. https://doi.org/10.1111/1574-6941.12223Koenig J.E., Spor A., Scalfone N., Fricker A.D., Stombaugh J. Succession of microbial consortia in the developing infant gut microbiome. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 4578-85. https://doi.org/10.1073/pnas.1000081107Aagaard K., Ma J., Antony K.M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci. Transl. Med. 2014; 6: 237. https://doi.org/10.1126/scitranslmed.3008599David L.A., Maurice C.F., Carmody R.N., Gootenberg D.B., Button J.E., Wolfe B.E. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2012; 505: 559-63. https://doi.org/10.1038/nature12820De Filippo C., Cavalieri D., Di Paola M., Ramazzotti M., Poullet J.B., Massart S. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 14691-6. https://doi.org/10.1073/pnas.1005963107Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project Nature. 2019; 569 (7758): 641-8. https://doi.org/10.1038/s41586-019-1238-8Bouhnik Y, Alain S., Attar A., Flourie B., Raskine L., Sanson-Le Pors M.J., Rambaud J.C. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999; 94: 1327-31. https://doi.org/10.1111/j.1572-0241.1999.01016.xGrace E., Shaw C., Whelan K., Andreyev H.J. Review article: small intestinal bacterial overgrowth prevalence, clinical features, current and developing diagnostic tests, and treatment. Aliment Pharmacol Ther. 2013; 38 (7): 88. https://doi.org/10.1111/apt.12456Sachdev, A.H. Gastrointestinal Bacterial Overgrowth Pathogenesis and Clinical Significance. Ther. Adv Chronic Dis. 2013; 4 (5): 22331. https://doi.org/10.1177/2040622313496126Quigley E.M. Small Intestinal Bacterial Overgrowth: What It Is and What It Is Not Current Opinion in Gastroenterology. 2014; 30 (2): 141-6. https://doi.org/10.1097/MOG.0000000000000040Hoog C.M., Lindberg G., Sjoqvist U. Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy BMC Gastroenterol. 2007; 7: 29. https://doi.org/10.1186/1471-230X-7-29Dibaise J.K., Young R.J., Vanderhoof J.A. Enteric microbial flora, bacterial overgrowth, and short-bowel syndrome. Clin Gastroenterol Hepatol. 2006; 4: 11-20. https://doi.org/10.1016/j.cgh.2005.10.020Nelis G.F, Vermeeren M.A., Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology. 1990; 99: 1016-20. https://doi.org/10.1016/0016-5085(90)90621-7Nucera G., Gabrielli M., Lupascu A., Lauritano E.C., Santoliquido A., Cremonini F, Cammarota G., Tondi P., Pola P., Gasbarrini G., Gasbarrini A. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2005; 21: 1391-5. https://doi.org/10.1111/j.1365-2036.2005.02493.x.Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, auto immunity and cancer. Physiol Rev. 2011; 91: 151-75. https://doi.org/10.1152/physrev.00003.2008Garate I., Garcia-Bueno В., Madrigal J.L.M. Origin and consequences of brain toll-like receptor 4 pathway stimulation in an experimental model of depression. J. Neuroinflamm. 2011; 8: 1-31. https://doi.org/10.1186/1742-2094-8-151.Gasbarrini A., Lauritano E.C., Gabrielli M., Scarpellini E., Lupascu A., Ojetti V, Gasbarrini G. Small intestinal bacterial overgrowth: diagnosis and treatment. Dig Dis. 2007; 25: 237-40. https://doi.org/10.1159/000103892.Fan X., Sellin J.H. Review article: Small intestinal bacterialovergrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhoea. Aliment Pharmacol Ther. 2009; 29: 1069-77. https://doi.org/10.1111/j.1365-2036.2009.03970.x.Vanderhoof J.A., Young R.J. Etiology and pathogenesis of bacterial overgrowth. J. Pediatr Gastroenterol Nutr. 2010; 50 (6): 88-90. https://doi.org/10.1097/MPG.0b013e3181c15f60Quera R.P. Small intestinal bacterial overgrowth. Rev. Med. Chil. 2005; 133: 1361-70. https://doi.org/10.4067/s0034-98872005001100013.Riordan S.M., McIver C.J., Walker B.M., Duncombe VM., Bolin T.D., Thomas M.C. The lactulose breath hydrogen test and small intestinal bacterial overgrowth. Am. J. Gastroenterol. 1996; 91: 1795-803. PMID: 8792701Kerlin P., Wong L. Breath hydrogen testing in bacterial overgrowth of the small intestine. Gastroenterology. 1988; 95: 982-8. https://doi.org/10.1016/0016-5085(88)90173-4.Gasbarrini A. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference Aliment. Pharmacol. Ther. 2009; 29 (1): 1-49. https://doi.org/10.1111/j.1365-2036.2009.03951.xShah S.C. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth Aliment. Pharmacol. Ther. 2013; 38 (8): 925-34. https://doi.org/10.1111/apt.12479Lauritano E.C., Gabrielli M., Scarpellini E., Lupascu A., Novi M., Sottili S., Vitale G., Cesario V, Serricchio M., Cammarota G., Gasbarrini G., Gasbarrini A. Small intestinal bacterial overgrowth recurrence after antibiotic therapy. Am. J. Gastroenterol. 2008; 103 (8): 2031-5. https://doi.org/10.1111/j.1572-0241.2008.02030.x.Barclay L. Benefits of probiotics reviewed. Am. Fam Physician. 2008; 78: 1073e8. PMID: 19007054Lin H.V., Frassetto A., Kowalik EJ. Jr., Nawrocki A.R., Lu M.M., Kosinski J.R., Hubert J.A., Szeto D., Yao X., Forrest G., Marsh D.J. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mecha nisms. PLoS One. 2012; 7 (4): 35240. https://doi.org/10.1371/journal.pone.0035240Samuelson D.R., Welsh D.A. and Shellito J.E. Regulation of lung immunity and host defense by the intestinal microbiota. Front. Microbiol. 2015; 6: 1085. https://doi.org/10.3389/fmicb.2015.01085Brown A.J. The Orphan G protein-coupled receptors GPR41 and GPR43 are activatedby propionate and other short chain carboxylic acids. J. Biol. Chem. 2003; 278 (13): 11312-9. https://doi.org/10.1074/jbc.M211609200Ang Z., Ding J. GPR41 and GPR43 in Obesity and Inflammation -Protective or Causative? Front Immunol. 2016; 7: 28. https://doi.org/10.3389/fimmu.2016.00028Larsen J.M., Steen-Jensen D.B., Laursen J.M. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota. PLoS One. 2012; 7 (2): 31976. https://doi.org/10.1371/journal.pone.0031976Arrieta M., Leah T. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Translational Medicine. 2015; 7: 307ra152. https://doi.org/10.1126/scitranslmed.aab2271Abrahamsson T.R., Jakobsson H.E., Andersson A.F., Bjorksten B., Engstrand L., Jenmalm M.C. Low gut microbiota diversity in early infancy precedes asthma at school age. ClinExp Allergy 2014; 44 (6): 842-50. https://doi.org/10.1111/cea.12253Kalliomaki M., Kirjavainen P., Eerola E., Kero P., Salminen S., Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J. Allergy Clinlmmunol. 2001; 1: 129-34. https://doi.org/10.1067/mai.2001.111237.Gerrard J.W., Vickers P., Gerrard C.D. The familial incidence of allergic disease. Ann Allergy 1976; 36: 10-5. PMID: 1247187Strachan D.P. Family size, infection and atopy: the first decade of the «hygiene hypothesis» Thorax. 2000; 55: 2-10. https://doi.org/10.1136/thorax.55.suppl_1.s2.Winkler P., Ghadimi D., Schrezenmeir J., Kraehenbuhl J.P. Molecular and cellular basis of microfloraehostinteractions. J. Nutr, 2007; 137: 756-72. https://doi.org/10.1093/jn/137.3.756STang R.B., Chen S.J. Soluble interleukin 2 receptor and interleukin 4 in sera of asthmatic children before and after a prednisolone course. Ann Allergy Asthma Immunol. 2001; 86 (3): 314-7. https://doi.org/10.1016/S1081-1206(10)63305-4.Herbst T., Sichelstiel A., Schar C., Yadava K., Burki K., Cahenzli J., McCoy K., Marsland B.J., Harris N.L. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respir Crit Care Med. 2011; 184 (2): 198-205. https://doi.org/10.1164/rccm.201010-1574OCDe Kivit S., Tobin M.C., DeMeo M.T. In vitro evaluation of intestinal epithelial TLR activation in preventing food allergic responses. Clin. Immunol. 2014; 154 (2): 91-9. https://doi.org/10.1016/j.clim.2014.07.002Bjorksten B., Naaber P., Sepp E., Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin. Exp Allergy 1999; 29: 342-6. https://doi.org/10.1046/j.1365-2222.1999.00560.x.Toh Z.Q., Anzela A., Tang M.L., Licciardi P.V. Probiotic therapy as a novel approach for allergic disease. Front Pharmacol. 2012; 3: 171. https://doi.org/10.3389/fphar.2012.00171Ventura M., Turroni F, Canchaya C., Vaughan E.E., O'Toole P.W., van Sinderen D. Microbial diversity in the human intestine and novel insights from metagenomics. Front Biosci (Landmark Ed). 2009; 14: 3214-21. https://doi.org/10.2741/3445Hevia A., Milani Ch., Lopez P., DonadoC. D. Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis. PLoS ONE. 2011; 11 (2): e0147809. https://doi.org/10.1371/journal.pone.0147809Rogers G.B., Wesselingh S. Precision respiratory medicine and the microbiome. Lancet Respir Med. 2016; 4 (1): 73-82. https://doi.org/10.1016/S2213-2600(15)00476-2.Venkataraman A., BassisCh.M., Beck J.M., Young V. B. Application of a Neutral Community Model To Assess Structuring of the Human Lung Microbiome. mBio. 2015; 6: 02284-14. https://doi.org/10.1128/mBio.02284-14.Trompette A., Gollwitzer E. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nature Medicine. 2014; 20: 159-66. https://doi.org/10.1038/nm.3444Ganesh В.Р., Versalovic J. Luminal Conversion and Immunoregulation by Probiotics. Front Pharmacol. 2015; 6: 269. https://doi.org/10.3389/fphar.2015.00269Isolauri E, Joensuu J, Suomalainen H, Luomala M, Vesikari T. Improved immunogenicity of oral DxRRVreassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine. 1995; 13: 310-2. https://doi.org/10.1016/0264-410x(95)93319-5.Smolinska S., Jutel M., Crameri R., O'Mahony L. Histamine and gut mucosal immune regulation. Allergy 2014; 6: 273-81. https://doi.org/10.1111/all.12330Barcik W., Wawrzyniak M., Akdis C., O'Mahony L. Immune regulation by histamine and histamine-secreting bacteria. Current Opinion in Immunology 2017; 48: 108-13. https://doi.org/10.1016/j.coi.2017.08.011Jutel M., Akdis M., Akdis C.A. Histamine, histamine receptors and their role in immune pathology. Clin. Exp Allergy. 2009; 39: 1786-800. https://doi.org/10.1111/j.1365-2222.2009.03374.xLiang X., Bushman FD., Fitz Gerald GA. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock. Proc Natl Acad Sci USA. 2015; 112 (33): 10479-84. https://doi.org/10.1073/pnas.1501305112Salyers A.A. Bacteroides of the human lower intestinaltract. Annu Rev Microbiol. 1984; 38: 293-313. https://doi.org/10.1146/annurevmi.38.100184.001453Hol J., van Leer E.H., Elink-Schuurman B.E., de Ruiter L.F., Samsom J.N., Hop W. et al. The acquisition of tolerance toward cow's milk through probiotic supplementation: a randomized, controlled trial. J. Allergy ClinImmunol. 2008; 121 (6): 1448-54. https://doi.org/10.1016/j.jaci.2008.03.018The Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome. Nature. 2012; 486: 207-14. https://doi.org/10.1038/nature11234.Kirjavainen P.V., Gibson G.R. Healthy gut microflora and allergy: factors influencing development of the microbiota. Ann Med. 1999; 31 (2): 88-92. https://doi.org/10.3109/07853899908995892Pande C., Kumar A., Sarin Pande S. K., C. Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease. Aliment. Pharmacol. Ther. 2009; 29 (12): 1273-81. https://doi.org/10.1111/j.1365-2036.2009.03994.x.Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A. World Allergy Organization-McMaster University Guidelines for allergic disease prevention (GLAD-P): probiotics. World Allergy Organ J. 2015; 8 (1): 4-10. https://doi.org/10.1186/s40413-015-0055-2Helin T., Haahtela S., Haahtela T. No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC 53103), on birch-pollen allergy: a placebo-controlled double-blind study. Allergy. 2002; 5: 243-6. https://doi.org/10.1034/j.1398-9995.2002.1s3299.x.Turnbaugh P., Ley R., Hamady M., Fraser-Liggett C., Knight R., Gordon J. Gordon Nature The human microbiome project: exploring the microbial part of ourselves in a changing world. PMC. 2013; 449 (7164): 804-10. https://doi.org/10.1038/nature06244Cabana M., McKean M., Caughey A., Fong L., Lynch L., Wong A., Leong R., Boushey H., Hiltonn J. Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial. Pediatrics. 2017; 140 (3): e20163000. https://doi.org/10.1542/peds.2016-3000Michail S. The role of probiotics in allergic diseases. Allergy Asthma ClinImmunol. 2009; 5 (1): 5. 10.1186/1710-1492-5-5.Giovannini M., Agostoni C., Riva E., Salvini F., Ruscitto A., Zuccotti G.V A randomized prospective double blind controlled trial on effects of long-term consumption of fermented milk containing Lactobacillus casei in pre-school children with allergic asthma and/or rhinitis. Pediatr Res. 2007; 62 (2): 15-20. https://doi.org/10.1203/ PDR.0b013e3180a76d94Ismai I.H., Licciardi P.V., Tang M.L.K. Probiotic effects in allergic disease. J. Paediatr Child Health. 2013; 49 (9): 709-15. https://doi.org/10.1111/jpc.12175Del Giudice M.M., Leonardi S., Maiello N., Brunese F.P. Food allergy and probiotics in childhood. J. Clin. Gastroenterol. 2010; 44: 22-5. https://doi.org/10.1097/MCG.0b013e3181e102a7Van de Pol M.A., Lutter R., Smids B.S., Weersink E.J., van der Zee J.S. Synbiotics reduce allergen-induced T-helper 2 response and improve peak expiratory flow in allergic asthmatics Allergy 2010; 66 (1): 39-47. https://doi.org/10.1111/j.1398-9995.2010.02454.x