gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2016-26-3-11-16gastro-j-55Research ArticleЛЕКЦИИ И ОБЗОРЫLECTURES AND REVIEWSРоль микробиома в развитии болезней пищеводаMicrobiome in development of esophageal diseasesЕвсютинаЮ. В.YevsyutinaYu. V.uselina@mail.ruИвашкинВ. Т.IvashkinV. T.noemail@neicon.ruГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» ;РоссияState educational government-financed institution of higher professional education «Sechenov First Moscow state medical university»Russian FederationГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова»РоссияState educational government-financed institution of higher professional education «Sechenov First Moscow state medical university»Russian Federation2016120820162631116Copyright © Евсютина Ю.В., Ивашкин В.Т., 20162016Евсютина Ю.В., Ивашкин В.Т.Yevsyutina Y.V., Ivashkin V.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/55

Цель обзора. Представить современные данные о роли микробиома в развитии различных заболеваний пищевода и возможностях его коррекции с помощью пробиотиков. Основные положения. Микробиом желудочно кишечного тракта представляет собой невидимый орган нашего организма, объединяющий порядка 1014 микроорганизмов. Основными типами бактерий пищевода являются Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria и TM7. Микробиом нормальной слизистой пищевода представлен грамположительными бактериями типа Firmicutes, микробиом у пациентов с пищеводом Баррета и эзофагитом - преимущественно грамотрицательными анаэробами из типа Bacteroidetes, Proteobacteria, Fusobacteria и Spirochaete, у больных с эозинофильным эзофагитом - Proteobacteria. Экспрессия опухолевых и воспалительных медиаторов (толлподобные рецепторы, интерлейкины, ядерный фактор κВ, циклооксигеназа-2) может быть обусловлена составом микробиома. Заключение. Результаты проведенных исследований свидетельствуют об изменении микробиома пищевода у пациентов с гастроэзофагеальной рефлюксной болезнью, пищеводом Баррета, аденокарциномой пищевода и эозинофильным эзофагитом. Потенциальными медиаторами воспаления и канцерогенеза выступают толл-подобные рецепторы, цитокины, ядерный фактор κВ, циклооксигеназа-2, экспрессия которых может модифицироваться в зависимости от состава микробиома. Приоритетным направлением в лечении пациентов с заболеваниями пищевода могут стать пробиотики.

Aim of review. To present up-to-date data on microbiome role in development of various esophageal diseases and options of probiotics application in esophageal diseases treatment. Summary. Gastro-intestinal microbiome is an invisible organ of our body integrating about 1014 microorganisms. Main bacteria types for the esophagus are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and TM7. The microbiome of the normal esophageal mucosa is represented by gram-positive bacteria like Firmicutes; microbiome in patients with Barret's esophagus and esophagitis is constituted mainly by gram-negative anaerobe bacteria: Bacteroidetes, Proteobacteria, Fusobacteria and Spirochaete; patients with eosinophilic esophagitis have Proteobacteria. Expression of tumor and inflammatory mediators (toll-like receptors, interleukins, nuclear factor κB, cyclooxygenase-2) can be determined by microbiome pattern. Conclusion. Results of original studies demonstrate microbiome changes of the esophagus at gastroesophageal reflux disease, Barret's esophagus, adenocarcinoma of the esophagus and eosinophilic esophagitis. Toll-like receptors, cytokines, nuclear factor κB, cyclooxygenase-2 can be potential mediators of inflammation and carcinogenesis which expression can be modified by microbiome spectrum. Probiotics can become the priority trend in treatment of diseases of the esophagus.

микробиомэзофагитпищевод Барретааденокарцинома пищеводаэозинофильный эзофагитпробиотикиReferencesШульпекова Ю.О. Кишечный микробиом как особый орган. Рос журн гастроэнтерол гепатол колопроктол 2014; 24(6):82-8.Шульпекова Ю.О. Кишечный микробиом как особый орган. Рос журн гастроэнтерол гепатол колопроктол 2014; 24(6):82-8.Полуэктова Е.А., Ляшенко О.С., Шифрин О.С., Шептулин А.А., Ивашкин В.Т. Современные методы изучения микрофлоры желудочно-кишечного тракта человека. Рос журн гастроэнтерол гепатол колопроктол 2014; 24(5):85-91.Полуэктова Е.А., Ляшенко О.С., Шифрин О.С., Шептулин А.А., Ивашкин В.Т. Современные методы изучения микрофлоры желудочно-кишечного тракта человека. Рос журн гастроэнтерол гепатол колопроктол 2014; 24(5):85-91.Ivashkin V., Drapkina O., Poluektova Ye., Kuchu- mova S., Sheptulin A., Shifrin O. The effect of a multi- strain probiotic on the symptoms and small intestinal bacterial overgrowth in constipation-predominant irritable bowel syndrome: A randomized, simple-blind, placebo- controlled trial. Am J Clin Med Res 2015; 3(2):18-23.Ivashkin V., Drapkina O., Poluektova Ye., Kuchu- mova S., Sheptulin A., Shifrin O. The effect of a multi- strain probiotic on the symptoms and small intestinal bacterial overgrowth in constipation-predominant irritable bowel syndrome: A randomized, simple-blind, placebo- controlled trial. Am J Clin Med Res 2015; 3(2):18-23.Gagliardi D., Makihara S., Corsi P.R., et al. Microbial flora of the normal esophagus. Diseases of the esophagus: official journal of the International Society for Diseases of the Esophagus / ISDE1998; 11:248-50.Gagliardi D., Makihara S., Corsi P.R., et al. Microbial flora of the normal esophagus. Diseases of the esophagus: official journal of the International Society for Diseases of the Esophagus / ISDE1998; 11:248-50.Oliver J.D. Recent findings on the viable but nonculturable state in pathogenic bacteria. FEMS microbiology reviews 2010; 34:415-25.Oliver J.D. Recent findings on the viable but nonculturable state in pathogenic bacteria. FEMS microbiology reviews 2010; 34:415-25.Pei Z., Bini E.J., Yang L., Zhou M., Francois F., Blaser M.J. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci USA 2004; 101:4250-5.Pei Z., Bini E.J., Yang L., Zhou M., Francois F., Blaser M.J. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci USA 2004; 101:4250-5.Yang L., Lu X., Nossa C.W., Francois F., Peek R.M., Pei Z. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology 2009; 137:588-97.Yang L., Lu X., Nossa C.W., Francois F., Peek R.M., Pei Z. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology 2009; 137:588-97.Liu N., Ando T., Ishiguro K., et al. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett’s esophagus. BMC Infect Dis 2013; 13:130-5.Liu N., Ando T., Ishiguro K., et al. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett’s esophagus. BMC Infect Dis 2013; 13:130-5.Amir I., Konikoff F.M., Oppenheim M., Gophna U., Half E.E. Gastric microbiota is altered in esophagitis and Barrett’s esophagus and further modified by proton pump inhibitors. Environ Microbiol 2013; 20:141-7Amir I., Konikoff F.M., Oppenheim M., Gophna U., Half E.E. Gastric microbiota is altered in esophagitis and Barrett’s esophagus and further modified by proton pump inhibitors. Environ Microbiol 2013; 20:141-7Rajilic-Stojanovic M., Biagi E., Heilig H.G., et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141(5):1792-801.Rajilic-Stojanovic M., Biagi E., Heilig H.G., et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011; 141(5):1792-801.Fischbach L.A., Graham D.Y., Kramer J.R., et al. Association between Helicobacter pylori and Barrett’s Esophagus: A Case-Control Study. Am J Gastroenterol 2014; 109(3):357-68.Fischbach L.A., Graham D.Y., Kramer J.R., et al. Association between Helicobacter pylori and Barrett’s Esophagus: A Case-Control Study. Am J Gastroenterol 2014; 109(3):357-68.Pohl H., Welch H.G. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005; 97:142-6.Pohl H., Welch H.G. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005; 97:142-6.Каприн А.Д., Старинский В.В., Петрова Г.В. Состояние онкологической помощи населению России в 2012 году. М.:ФГУ «МНИОИ им. П.А. Герцена Минздравсоцразвития России» 2014. 260 с.Каприн А.Д., Старинский В.В., Петрова Г.В. Состояние онкологической помощи населению России в 2012 году. М.:ФГУ «МНИОИ им. П.А. Герцена Минздравсоцразвития России» 2014. 260 с.Ивашкин В.Т., Маев И.В., Трухманов А.С., Соколов В.В., Пирогов С.С., Зайратьянц О.В., Шептулин А.А., Лапина Т.Л., Зайратьянц Г.О., Кайбышева В.О. Пищевод Баррета. Клинические реко- мендации. Российская гастроэнтерологическая ассоциа- ция 2014. М., 31 с.Ивашкин В.Т., Маев И.В., Трухманов А.С., Соколов В.В., Пирогов С.С., Зайратьянц О.В., Шептулин А.А., Лапина Т.Л., Зайратьянц Г.О., Кайбышева В.О. Пищевод Баррета. Клинические реко- мендации. Российская гастроэнтерологическая ассоциа- ция 2014. М., 31 с.Baghdadi J., Chaudhary N., Pei Z., Yang L. Microbiome, innate immunity, and esophageal adenocarcinoma. Clin Lab Med 2014; 34(4):721-32.Baghdadi J., Chaudhary N., Pei Z., Yang L. Microbiome, innate immunity, and esophageal adenocarcinoma. Clin Lab Med 2014; 34(4):721-32.Oh D.S., DeMeester S.R., Vallbohmer D., et al. Reduc- tion of interleukin 8 gene expression in reflux esophagitis and Barrett’s esophagus with antireflux surgery. Arch Surg 2007; 142:554-9.Oh D.S., DeMeester S.R., Vallbohmer D., et al. Reduc- tion of interleukin 8 gene expression in reflux esophagitis and Barrett’s esophagus with antireflux surgery. Arch Surg 2007; 142:554-9.O’Riordan J.M., Abdel-latif M.M., Ravi N., et al.O’Riordan J.M., Abdel-latif M.M., Ravi N., et al.Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia- adenocarcinoma sequence in the esophagus. Am J Gastroenterol 2005; 100:1257-64.Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia- adenocarcinoma sequence in the esophagus. Am J Gastroenterol 2005; 100:1257-64.Isomoto H., Inoue K., Kohno S. Interleukin-8 levels in esophageal mucosa and long-term clinical outcome of patients with reflux esophagitis. Scand J Gastroenterol 2007; 42:410-1.Isomoto H., Inoue K., Kohno S. Interleukin-8 levels in esophageal mucosa and long-term clinical outcome of patients with reflux esophagitis. Scand J Gastroenterol 2007; 42:410-1.Ivashkin V., Evsyutina Y., Trukhmanov A., Lyamina S., Malyshev I. Systemic inflammatory response in patients with gastroesophageal reflux disease. Am J Clin Med Res 2015; 3(4):64-9.Ivashkin V., Evsyutina Y., Trukhmanov A., Lyamina S., Malyshev I. Systemic inflammatory response in patients with gastroesophageal reflux disease. Am J Clin Med Res 2015; 3(4):64-9.Blackett K.L., Siddhi S.S., Cleary S., Steed H., Mil- ler M.H., Macfarlane S., Macfarlane G.T., Dillon J.F. Esophageal bacterial biofilm changes in gastroesophageal reflux disease, Barrett’s and esophageal carcinoma: association or causality? Aliment Pharmacol Ther 2013; 37(11):1084-92.Blackett K.L., Siddhi S.S., Cleary S., Steed H., Mil- ler M.H., Macfarlane S., Macfarlane G.T., Dillon J.F. Esophageal bacterial biofilm changes in gastroesophageal reflux disease, Barrett’s and esophageal carcinoma: association or causality? Aliment Pharmacol Ther 2013; 37(11):1084-92.Babar M., Ryan A.W., Anderson L.A., Segurado R., Turner G., Murray L.J., Murphy S.J., Johnston B.T., Comber H., Reynolds J.V., McManus R. Genes of the interleukin-18 pathway are associated with susceptibility to Barrett’s esophagus and esophageal adenocarcinoma. Am J Gastroenterol 2012; 107(9):1331-41.Babar M., Ryan A.W., Anderson L.A., Segurado R., Turner G., Murray L.J., Murphy S.J., Johnston B.T., Comber H., Reynolds J.V., McManus R. Genes of the interleukin-18 pathway are associated with susceptibility to Barrett’s esophagus and esophageal adenocarcinoma. Am J Gastroenterol 2012; 107(9):1331-41.Yang L., Francois F., Pei Z. Molecular Pathways: Pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett’s esophagus. Clin Cancer Res 2012; 18(8):2138-44.Yang L., Francois F., Pei Z. Molecular Pathways: Pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett’s esophagus. Clin Cancer Res 2012; 18(8):2138-44.Zhou X., Li D., Resnick M.B., Wands J., Cao W. NADPH oxidase NOX5-S and nuclear factor kappaB1 mediate acid-induced microsomal prostaglandin E synthase-1 expression in Barrett’s esophageal adenocarcinoma cells. Mol Pharmacol 2013; 83:978-90.Zhou X., Li D., Resnick M.B., Wands J., Cao W. NADPH oxidase NOX5-S and nuclear factor kappaB1 mediate acid-induced microsomal prostaglandin E synthase-1 expression in Barrett’s esophageal adenocarcinoma cells. Mol Pharmacol 2013; 83:978-90.Zaidi A.H., Kelly L.A., Kreft R.E., Barlek M., Omstead A.N., Matsui D., Boyd N.H., Gazarik K.E., Heit M.I., Nistico L., Kasi P.M., Spirk T.L., Byers B., Lloyd E.J., Landreneau R.J., Jobe B.A. Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma. BMC Cancer 2016; 16(1):52.Zaidi A.H., Kelly L.A., Kreft R.E., Barlek M., Omstead A.N., Matsui D., Boyd N.H., Gazarik K.E., Heit M.I., Nistico L., Kasi P.M., Spirk T.L., Byers B., Lloyd E.J., Landreneau R.J., Jobe B.A. Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma. BMC Cancer 2016; 16(1):52.Sherrill J.D., Kc K., Wu D., Djukic Z., Caldwell J.M., Stucke E.M., et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol 2014; 7(3):718-Sherrill J.D., Kc K., Wu D., Djukic Z., Caldwell J.M., Stucke E.M., et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol 2014; 7(3):718-Yousefi S., Gold J.A., Andina N., Lee J.J., Kelly A.M., Kozlowski E., et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Natl Med 2008; 14(9):949-53.Yousefi S., Gold J.A., Andina N., Lee J.J., Kelly A.M., Kozlowski E., et al. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Natl Med 2008; 14(9):949-53.Harris K.J., Fang R., Wagner D., Choe H.N., Kelly C.J., Schroeder S., et al. Esophageal microbiome in eosinophilic esophagitis. PLoS One 2015; 10(5):e0128346.Harris K.J., Fang R., Wagner D., Choe H.N., Kelly C.J., Schroeder S., et al. Esophageal microbiome in eosinophilic esophagitis. PLoS One 2015; 10(5):e0128346.Stefka A.T., Feehley T., Tripathi P., Qiu J., McCoy K., Mazmanian S.K., et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci USA 2014; 111(36):13145-50.Stefka A.T., Feehley T., Tripathi P., Qiu J., McCoy K., Mazmanian S.K., et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci USA 2014; 111(36):13145-50.Cao A.T., Yao S., Stefka A.T., Liu Z., Qin H., Liu H., et al. TLR4 regulates IFN-gamma and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation. J Leukoc Biol 2014; 96:895-905.Cao A.T., Yao S., Stefka A.T., Liu Z., Qin H., Liu H., et al. TLR4 regulates IFN-gamma and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation. J Leukoc Biol 2014; 96:895-905.Benitez A.J., Hoffmann C.M., Muir A.B., Dods K.K., Spergel J.M., et al. Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome 2015; 3:23.Benitez A.J., Hoffmann C.M., Muir A.B., Dods K.K., Spergel J.M., et al. Inflammation-associated microbiota in pediatric eosinophilic esophagitis. Microbiome 2015; 3:23.Mozaffari N.B., Daryani N.E., Mirshafiey A., Yazdi M.K., Dallal M.M. Effect of probiotics on the expression of Barrett’s esophagus biomarkers. J Med Microbiol 2015; 64(4):348-54.Mozaffari N.B., Daryani N.E., Mirshafiey A., Yazdi M.K., Dallal M.M. Effect of probiotics on the expression of Barrett’s esophagus biomarkers. J Med Microbiol 2015; 64(4):348-54.Madsen, K.L. Enhancement of epithelial barrier function by probiotics. J Epithel Biol Pharmacol 2012; 5:55-9.Madsen, K.L. Enhancement of epithelial barrier function by probiotics. J Epithel Biol Pharmacol 2012; 5:55-9.Smith A.R., Macfarlane G.T., Reynolds N., O’May G.A., Bahrami B. Macfarlane S. Effect of a synbiotic on microbial community structure in a continuous culture model of the gastric microbiota in enteral nutrition patients. FEMS Microbiol Ecol 2012; 80:135-45.Smith A.R., Macfarlane G.T., Reynolds N., O’May G.A., Bahrami B. Macfarlane S. Effect of a synbiotic on microbial community structure in a continuous culture model of the gastric microbiota in enteral nutrition patients. FEMS Microbiol Ecol 2012; 80:135-45.Quigley E.M. Prebiotics and probiotics:their role in the management of gastrointestinal disorders in adults. Nutr Clin Pract 2012; 27:195-200.Quigley E.M. Prebiotics and probiotics:their role in the management of gastrointestinal disorders in adults. Nutr Clin Pract 2012; 27:195-200.

The authors declare that there are no conflicts of interest present.