ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2024-1-166-175ssmu-5539Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESОсобенности микробиоты легких при туберкулезной инфекцииFeatures of the lung microbiota in tuberculosis infectionhttps://orcid.org/0000-0003-2169-0242ОрловаЕ. А.OrlovaE. A.

Орлова Елизавета Андреевна – аспирант, мл. науч. сотрудник, лаборатория эпидемиологически и социально значимых инфекций, Институт эпидемиологии и микробиологии

664003, г. Иркутск, ул. Тимирязева, 16

16, Timiryazeva Str., Irkutsk, 664003

elizaveta.a.orlova@gmail.comhttps://orcid.org/0000-0002-3168-1983ОгарковО. Б.OgarkovO. B.

Огарков Олег Борисович – д-р мед. наук, директор Института эпидемиологии и микробиологии

664003, г. Иркутск, ул. Тимирязева, 16

16, Timiryazeva Str., Irkutsk, 664003

obogarkov@mail.ruhttps://orcid.org/0000-0003-3354-2992КолесниковаЛ. И.KolesnikovaL. I.

Колесникова Любовь Ильинична – д-р мед. наук, профессор, академик РАН, науч. руководитель

664003, г. Иркутск, ул. Тимирязева, 16

16, Timiryazeva Str., Irkutsk, 664003

iphr@sbamsr.irk.ruНаучный центр проблем здоровья семьи и репродукции человека (НЦ ПЗСРЧ)РоссияScientific Center for Family Health and Human Reproduction Problems (SC FHHRP)Russian Federation202411042024231166175Copyright © Орлова Е.А., Огарков О.Б., Колесникова Л.И., 20242024Орлова Е.А., Огарков О.Б., Колесникова Л.И.Orlova E.A., Ogarkov O.B., Kolesnikova L.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/5539

Микробиота легких представляет собой маятник, который колеблется между двумя статическими состояниями – от небольшого количества транзиторных микробов в норме до моделей устойчивой микробной колонизации при патологии. Микробиота легких остается малоизученной и загадочной частью патогенеза туберкулезной инфекции.

В настоящем обзоре отражены общие патогенетические механизмы влияния микробиоты легких при респираторной патологии и представлены основные методологические трудности в изучении легочного микробиома. Рассмотрены результаты доступных исследований, посвященных изучению особенностей микробного разнообразия легких человека при туберкулезе с применением методов метагеномного секвенирования. Несмотря на высокую вариабельность представленных данных, дисбиоз при туберкулезе чаще характеризуется снижением бактериального разнообразия и обогащением легочной микробиоты анаэробными представителями. Acinetobacter, Campylobacter, Moraxella, Pseudomonas, Staphylococcus и Streptococcus, а также некоторые другие микроорганизмы указываются как важные патогенетические факторы дисбиоза при туберкулезе легких, роль которых еще предстоит выяснить.

Normal lung microbiota is a small number of transient microbes; however, respiratory pathology may be associated with persistent microbial colonization of the lungs. It remains a poorly understood and mysterious part of the pathogenesis of tuberculosis infection.

The review considers the general pathogenetic mechanisms of the effect of lung microbiota in respiratory pathology and presents the main methodological difficulties in the study of the lung microbiome. This review is aimed at analyzing the results of the available studies on diverse microbial composition of human lungs in tuberculosis using metagenomic sequencing methods. Despite high variability of the presented data, we can conclude that dysbiosis in tuberculosis is more often characterized by a decrease in bacterial diversity and enrichment of lung microbiota with anaerobic bacteria. Acinetobacter, Campylobacter, Moraxella, Pseudomonas, Staphylococcus, and Streptococcus, as well as some other microorganisms are indicated as important pathogenetic factors of dysbiosis in pulmonary tuberculosis, the role of which is yet to be elucidated.

 

микробиотамикробиомлегкиетуберкулезметагеномикаmicrobiotamicrobiomelungstuberculosismetagenomicsРабота выполнена в рамках темы государственного задания № 121022500179-0The study was carried out within state assignment No. 121022500179-0ReferencesRogan M.P., Geraghty P., Greene C.M., O’Neill S.J., Taggart C.C., McElvaney N.G. Antimicrobial proteins and polypeptides in pulmonary innate defence. Respir. Res. 2006;7(1):29. DOI: 10.1186/1465-9921-7-29.Rogan M.P., Geraghty P., Greene C.M., O’Neill S.J., Taggart C.C., McElvaney N.G. Antimicrobial proteins and polypeptides in pulmonary innate defence. Respir. Res. 2006;7(1):29. DOI: 10.1186/1465-9921-7-29.Cvejic L., Harding R., Churchward T., Turton A., Finlay P., Massey D. et al. Laryngeal penetration and aspiration in individuals with stable COPD. Respirology. 2011;16(2):269–275. DOI: 10.1111/j.1440-1843.2010.01875.x.Cvejic L., Harding R., Churchward T., Turton A., Finlay P., Massey D. et al. Laryngeal penetration and aspiration in individuals with stable COPD. Respirology. 2011;16(2):269–275. DOI: 10.1111/j.1440-1843.2010.01875.x.Field S.K., Underwood M., Brant R., Cowie R.L. Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996;109(2):316–322. DOI: 10.1378/CHEST.109.2.316.Field S.K., Underwood M., Brant R., Cowie R.L. Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996;109(2):316–322. DOI: 10.1378/CHEST.109.2.316.Scott R.B., O’Loughlin E. V., Gall D.G. Gastroesophageal reflux in patients with cystic fibrosis. J. Pediatr. 1985;106(2):223– 227. DOI: 10.1016/s0022-3476(85)80291-2.Scott R.B., O’Loughlin E. V., Gall D.G. Gastroesophageal reflux in patients with cystic fibrosis. J. Pediatr. 1985;106(2):223– 227. DOI: 10.1016/s0022-3476(85)80291-2.Morse C.A., Quan S.F., Mays M.Z., Green C., Stephen G., Fass R. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin. Gastroenterol. Hepatol. 2004;2(9):761–768. DOI: 10.1016/s1542-3565(04)00347-7.Morse C.A., Quan S.F., Mays M.Z., Green C., Stephen G., Fass R. Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease? Clin. Gastroenterol. Hepatol. 2004;2(9):761–768. DOI: 10.1016/s1542-3565(04)00347-7.Koh W.J., Lee J.H., Kwon Y.S., Lee K.S., Suh G.Y., Chung M.P. et al. Prevalence of gastroesophageal reflux disease in patients with nontuberculous mycobacterial lung disease. Chest. 2007;131(6):1825–1830. DOI: 10.1378/chest.06-2280.Koh W.J., Lee J.H., Kwon Y.S., Lee K.S., Suh G.Y., Chung M.P. et al. Prevalence of gastroesophageal reflux disease in patients with nontuberculous mycobacterial lung disease. Chest. 2007;131(6):1825–1830. DOI: 10.1378/chest.06-2280.Beck J.M., Schloss P.D., Venkataraman A., Twigg H., Jablonski K.A., Bushman F.D. et al. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am. J. Respir. Crit. Care Med. 2015;192(11):1335– 1344. DOI: 10.1164/rccm.201501-0128OC.Beck J.M., Schloss P.D., Venkataraman A., Twigg H., Jablonski K.A., Bushman F.D. et al. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am. J. Respir. Crit. Care Med. 2015;192(11):1335– 1344. DOI: 10.1164/rccm.201501-0128OC.Kovaleva O.V., Kushlinskii N.E., Podlesnaya P.A., Stilidi I.S., Gratchev A.N. Diagnostic and prognostic potential of the resident non-small cell lung cancer microbiome. Klin. Lab. Diagn. 2022;67(8):458–462. DOI: 10.51620/0869-2084-2022-67-8-458-462.Kovaleva O.V., Kushlinskii N.E., Podlesnaya P.A., Stilidi I.S., Gratchev A.N. Diagnostic and prognostic potential of the resident non-small cell lung cancer microbiome. Klin. Lab. Diagn. 2022;67(8):458–462. DOI: 10.51620/0869-2084-2022-67-8-458-462.Огарков О.Б., Бадлеева М.В., Белькова Н.Л., Адельшин Р.В., Цыренова Т.А., Хромова П.А. и др. Феномен образования биопленок штаммами Brevibacillus spp. и Bacillus spp. в присутствии клинических штаммов Mycobacterium tuberculosis. Молекулярная генетика, микробиология и вирусология. 2017;35(3):103. DOI: 10.18821/0208-0613-2017-35-3-98-103.Огарков О.Б., Бадлеева М.В., Белькова Н.Л., Адельшин Р.В., Цыренова Т.А., Хромова П.А. и др. Феномен образования биопленок штаммами Brevibacillus spp. и Bacillus spp. в присутствии клинических штаммов Mycobacterium tuberculosis. Молекулярная генетика, микробиология и вирусология. 2017;35(3):103. DOI: 10.18821/0208-0613-2017-35-3-98-103.Огарков О., Суздальницкий А., Хромова П., Цыренова Т., Сокольникова Н., Жданова С. и др. Продукция биофильмов клиническими штаммами возбудителя туберкулеза. Инфекция и иммунитет. 2018;8(4):435–440. DOI: 10.15789/2220-7619-2018.Огарков О., Суздальницкий А., Хромова П., Цыренова Т., Сокольникова Н., Жданова С. и др. Продукция биофильмов клиническими штаммами возбудителя туберкулеза. Инфекция и иммунитет. 2018;8(4):435–440. DOI: 10.15789/2220-7619-2018.Орлова Е.А., Огарков О.Б., Суздальницкий А.Е., Хромова П.А., Синьков В.В., Плотников А.О. и др. Анализ микробного разнообразия казеозного некроза туберкулезных очагов. Молекулярная генетика, микробиология и вирусология. 2021;39(3):18–24. DOI: 10.17116/molgen20213903118.Орлова Е.А., Огарков О.Б., Суздальницкий А.Е., Хромова П.А., Синьков В.В., Плотников А.О. и др. Анализ микробного разнообразия казеозного некроза туберкулезных очагов. Молекулярная генетика, микробиология и вирусология. 2021;39(3):18–24. DOI: 10.17116/molgen20213903118.Пузанов В.А., Комиссарова О.Г., Никоненко Б.В. Бактериальная микробиота нижних отделов кишечника и бронхов у больных туберкулезом. Туберкулез и болезни легких. 2020;98(5):37–43. DOI: 10.21292/2075-1230-2020-98-5-37-43.Пузанов В.А., Комиссарова О.Г., Никоненко Б.В. Бактериальная микробиота нижних отделов кишечника и бронхов у больных туберкулезом. Туберкулез и болезни легких. 2020;98(5):37–43. DOI: 10.21292/2075-1230-2020-98-5-37-43.Каюкова С.И., Панова А.Е., Авербах М.М., Никоненко Б.В., Грачева А.Н., Компанцева Н.И. и др. Состояние легочной микробиоты у мышей С57bl/6 в модели экспериментального туберкулеза. Туберкулез и болезни легких. 2023;101(2):94–99. DOI: 10.58838/2075-1230-2023-101-2-94-99.Каюкова С.И., Панова А.Е., Авербах М.М., Никоненко Б.В., Грачева А.Н., Компанцева Н.И. и др. Состояние легочной микробиоты у мышей С57bl/6 в модели экспериментального туберкулеза. Туберкулез и болезни легких. 2023;101(2):94–99. DOI: 10.58838/2075-1230-2023-101-2-94-99.Mokrousov I., Chernyaeva E., Vyazovaya A., Sinkov V., Zhuravlev V., Narvskaya O.N. Next-generation sequencing of Mycobacterium tuberculosis. Emerg. Infect. Dis. 2016;22(6):1127–1129. DOI: 10.3201/eid2206.152051.Mokrousov I., Chernyaeva E., Vyazovaya A., Sinkov V., Zhuravlev V., Narvskaya O.N. Next-generation sequencing of Mycobacterium tuberculosis. Emerg. Infect. Dis. 2016;22(6):1127–1129. DOI: 10.3201/eid2206.152051.Sinkov V.V., Ogarkov O.B., Plotnikov A.O., Gogoleva N.E., Zhdanova S.N., Pervanchuk V.L. et al. Metagenomic analysis of mycobacterial transrenal DNA in patients with HIV and tuberculosis coinfection. Infect. Genet. Evol. 2020;77:104057. DOI: 10.1016/j.meegid.2019.104057.Sinkov V.V., Ogarkov O.B., Plotnikov A.O., Gogoleva N.E., Zhdanova S.N., Pervanchuk V.L. et al. Metagenomic analysis of mycobacterial transrenal DNA in patients with HIV and tuberculosis coinfection. Infect. Genet. Evol. 2020;77:104057. DOI: 10.1016/j.meegid.2019.104057.Galeeva J., Babenko V., Bakhtyev R., Baklaushev V., Balykova L., Bashkirov P. et al. 16S rRNA gene sequencing data of the upper respiratory tract microbiome in the SARS-CoV-2 infected patients. Data Br. 2022;40. DOI: 10.1016/j.dib.2021.107770.Galeeva J., Babenko V., Bakhtyev R., Baklaushev V., Balykova L., Bashkirov P. et al. 16S rRNA gene sequencing data of the upper respiratory tract microbiome in the SARS-CoV-2 infected patients. Data Br. 2022;40. DOI: 10.1016/j.dib.2021.107770.Worlitzsch D., Tarran R., Ulrich M., Schwab U., Cekici A., Meyer K.C. et al. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J. Clin. Invest. 2002;109(3):317–325. DOI: 10.1172/jci13870.Worlitzsch D., Tarran R., Ulrich M., Schwab U., Cekici A., Meyer K.C. et al. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J. Clin. Invest. 2002;109(3):317–325. DOI: 10.1172/jci13870.Kanangat S., Meduri G.U., Tolley E.A., Patterson D.R., Meduri C.U., Pak C. et al. Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infect. Immun. 1999;67(6): 2834–2840. DOI: 10.1128/iai.67.6.2834-2840.1999.Kanangat S., Meduri G.U., Tolley E.A., Patterson D.R., Meduri C.U., Pak C. et al. Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infect. Immun. 1999;67(6): 2834–2840. DOI: 10.1128/iai.67.6.2834-2840.1999.Segal L.N., Clemente J.C., Tsay J.C.J., Koralov S.B., Keller B.C., Wu B.G. et al. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat. Microbiol. 2016;1:16031. DOI: 10.1038/nmicrobiol.2016.31.Segal L.N., Clemente J.C., Tsay J.C.J., Koralov S.B., Keller B.C., Wu B.G. et al. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat. Microbiol. 2016;1:16031. DOI: 10.1038/nmicrobiol.2016.31.Marsland B.J., Gollwitzer E.S. Host-microorganism interactions in lung diseases. Nat. Rev. Immunol. 2014;14(12):827– 835. DOI: 10.1038/nri3769.Marsland B.J., Gollwitzer E.S. Host-microorganism interactions in lung diseases. Nat. Rev. Immunol. 2014;14(12):827– 835. DOI: 10.1038/nri3769.Dickson R.P., Erb-Downward J.R., Martinez F.J., Huffnagle G.B. The microbiome and the respiratory tract. Annu. Rev. Physiol. 2016;78:481–504. DOI: 10.1146/annurev-physiol-021115-105238.Dickson R.P., Erb-Downward J.R., Martinez F.J., Huffnagle G.B. The microbiome and the respiratory tract. Annu. Rev. Physiol. 2016;78:481–504. DOI: 10.1146/annurev-physiol-021115-105238.Ulrichs T., Kaufmann S.H.E. New insights into the function of granulomas in human tuberculosis. J. Pathol. 2006;208(2):261–269. DOI: 10.1002/path.1906.Ulrichs T., Kaufmann S.H.E. New insights into the function of granulomas in human tuberculosis. J. Pathol. 2006;208(2):261–269. DOI: 10.1002/path.1906.Domingue J.C., Drewes J.L., Merlo C.A., Housseau F., Sears C.L. Host responses to mucosal biofilms in the lung and gut. Mucosal. Immunol. 2020;13(3):413–422. DOI: 10.1038/s41385-020-0270-1.Domingue J.C., Drewes J.L., Merlo C.A., Housseau F., Sears C.L. Host responses to mucosal biofilms in the lung and gut. Mucosal. Immunol. 2020;13(3):413–422. DOI: 10.1038/s41385-020-0270-1.Bjarnsholt T., Jensen P.Ø., Fiandaca M.J., Pedersen J., Hansen C.R., Andersen C.B. et al. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol. 2009;44(6):547–558. DOI: 10.1002/ppul.21011.Bjarnsholt T., Jensen P.Ø., Fiandaca M.J., Pedersen J., Hansen C.R., Andersen C.B. et al. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol. 2009;44(6):547–558. DOI: 10.1002/ppul.21011.Starner T.D., Zhang N., Kim G.H., Apicella M.A., McCray P.B. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am. J. Respir. Crit. Care Med. 2006;174(2):213–220. DOI: 10.1164/rccm.200509-1459OC.Starner T.D., Zhang N., Kim G.H., Apicella M.A., McCray P.B. Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am. J. Respir. Crit. Care Med. 2006;174(2):213–220. DOI: 10.1164/rccm.200509-1459OC.Воронкова О.В., Уразова О.И., Новицкий В.В., Чурина Е.Г., Хасанова Р.Р., Наследникова И.О. и др. Особенности иммунного дисбаланса при различных клиникопатогенетических вариантах остропрогрессирующего туберкулеза легких. Бюллетень сибирской медицины. 2010;9(3):42–50. DOI: 10.20538/1682-0363-2010-3-42-5027.Воронкова О.В., Уразова О.И., Новицкий В.В., Чурина Е.Г., Хасанова Р.Р., Наследникова И.О. и др. Особенности иммунного дисбаланса при различных клиникопатогенетических вариантах остропрогрессирующего туберкулеза легких. Бюллетень сибирской медицины. 2010;9(3):42–50. DOI: 10.20538/1682-0363-2010-3-42-5027.Urazova O.I., Smolyagina R.R., Churina E.G., Novitskiy V.V. The factors of dendritic cells dysfunction at pulmonary tuberculosis. 2018;25(3):230. DOI: 10.1016/j.pathophys.2018.07.150.Urazova O.I., Smolyagina R.R., Churina E.G., Novitskiy V.V. The factors of dendritic cells dysfunction at pulmonary tuberculosis. 2018;25(3):230. DOI: 10.1016/j.pathophys.2018.07.150.Naidoo C.C., Nyawo G.R., Wu B.G., Walzl G., Warren R.M., Segal L.N. et al. The microbiome and tuberculosis: state of the art, potential applications, and defining the clinical research agenda. Lancet Respir. Med. 2019;7(10):892–906. DOI: 10.1016/s2213-2600(18)30501-0.Naidoo C.C., Nyawo G.R., Wu B.G., Walzl G., Warren R.M., Segal L.N. et al. The microbiome and tuberculosis: state of the art, potential applications, and defining the clinical research agenda. Lancet Respir. Med. 2019;7(10):892–906. DOI: 10.1016/s2213-2600(18)30501-0.Balcells M.E., Yokobori N., Hong B., Corbett J., Cervantes J. The lung microbiome, vitamin D, and the tuberculous granuloma: A balance triangle. Microb. Pathog. 2019;131:158–163. DOI: 10.1016/j.micpath.2019.03.041.Balcells M.E., Yokobori N., Hong B., Corbett J., Cervantes J. The lung microbiome, vitamin D, and the tuberculous granuloma: A balance triangle. Microb. Pathog. 2019;131:158–163. DOI: 10.1016/j.micpath.2019.03.041.Shah T., Shah Z., Baloch Z., Cui X.M. The role of microbiota in respiratory health and diseases, particularly in tuberculosis. Biomed. Pharmacother. 2021;143:112108. DOI: 10.1016/j.biopha.2021.112108.Shah T., Shah Z., Baloch Z., Cui X.M. The role of microbiota in respiratory health and diseases, particularly in tuberculosis. Biomed. Pharmacother. 2021;143:112108. DOI: 10.1016/j.biopha.2021.112108.Comberiati P., Di Cicco M., Paravati F., Pelosi U., Di Gangi A., Arasi S. et al. The role of gut and lung microbiota in susceptibility to tuberculosis. Int. J. Environ. Res. Public Health. 2021;18(22):12220. DOI: 10.3390/ijerph182212220.Comberiati P., Di Cicco M., Paravati F., Pelosi U., Di Gangi A., Arasi S. et al. The role of gut and lung microbiota in susceptibility to tuberculosis. Int. J. Environ. Res. Public Health. 2021;18(22):12220. DOI: 10.3390/ijerph182212220.Cui Z., Zhou Y., Li H., Zhang Y., Zhang S., Tang S. et al. Complex sputum microbial composition in patients with pulmonary tuberculosis. BMC Microbiol. 2012;12:276. DOI: 10.1186/1471-2180-12-276.Cui Z., Zhou Y., Li H., Zhang Y., Zhang S., Tang S. et al. Complex sputum microbial composition in patients with pulmonary tuberculosis. BMC Microbiol. 2012;12:276. DOI: 10.1186/1471-2180-12-276.Valdez-Palomares F., Torrico M.M., Palacios-González B., Soberón X., Silva-Herzog E. Altered microbial composition of drug-sensitive and drug-resistant TB patients compared with healthy volunteers. Microorganisms. 2021;9(8):1762. DOI: 10.3390/microorganisms9081762.Valdez-Palomares F., Torrico M.M., Palacios-González B., Soberón X., Silva-Herzog E. Altered microbial composition of drug-sensitive and drug-resistant TB patients compared with healthy volunteers. Microorganisms. 2021;9(8):1762. DOI: 10.3390/microorganisms9081762.Wu J., Liu W., He L., Huang F., Chen J., Cui P. et al. Sputum microbiota associated with new, recurrent and treatment failure tuberculosis. PLoS One. 2013;8(12):83445. DOI: 10.1371/journal.pone.0083445.Wu J., Liu W., He L., Huang F., Chen J., Cui P. et al. Sputum microbiota associated with new, recurrent and treatment failure tuberculosis. PLoS One. 2013;8(12):83445. DOI: 10.1371/journal.pone.0083445.Vázquez-Pérez J.A., Carrillo C.O., Iñiguez-García M.A., Romero-Espinoza I., Márquez-García J.E. et al. Alveolar microbiota profile in patients with human pulmonary tuberculosis and interstitial pneumonia. Microb. Pathog. 2020;139:103851. DOI: 10.1016/j.micpath.2019.103851.Vázquez-Pérez J.A., Carrillo C.O., Iñiguez-García M.A., Romero-Espinoza I., Márquez-García J.E. et al. Alveolar microbiota profile in patients with human pulmonary tuberculosis and interstitial pneumonia. Microb. Pathog. 2020;139:103851. DOI: 10.1016/j.micpath.2019.103851.Hu Y., Kang Y., Liu X., Cheng M., Dong J., Sun L. et al. Distinct lung microbial community states in patients with pulmonary tuberculosis. Sci. China Life Sci. 2020;63(10):1522– 1533. DOI: 10.1007/s11427-019-1614-0.Hu Y., Kang Y., Liu X., Cheng M., Dong J., Sun L. et al. Distinct lung microbial community states in patients with pulmonary tuberculosis. Sci. China Life Sci. 2020;63(10):1522– 1533. DOI: 10.1007/s11427-019-1614-0.Hu Y., Cheng M., Liu B., Dong J., Sun L., Yang J. et al. Metagenomic analysis of the lung microbiome in pulmonary tuberculosis – a pilot study. Emerg. Microbes Infect. 2020;9(1):1444– 1452. DOI: 10.1080/22221751.2020.1783188.Hu Y., Cheng M., Liu B., Dong J., Sun L., Yang J. et al. Metagenomic analysis of the lung microbiome in pulmonary tuberculosis – a pilot study. Emerg. Microbes Infect. 2020;9(1):1444– 1452. DOI: 10.1080/22221751.2020.1783188.Xiao G., Cai Z., Guo Q., Ye T., Tang Y., Guan P. et al. Insights into the unique lung microbiota profile of pulmonary tuberculosis patients using metagenomic next-generation sequencing. Microbiol .Spectr. 2022;10(1):e01901-21. DOI: 10.1128/spectrum.01901-21.Xiao G., Cai Z., Guo Q., Ye T., Tang Y., Guan P. et al. Insights into the unique lung microbiota profile of pulmonary tuberculosis patients using metagenomic next-generation sequencing. Microbiol .Spectr. 2022;10(1):e01901-21. DOI: 10.1128/spectrum.01901-21.Ueckermann V., Lebre P., Geldenhuys J., Hoosien E., Cowan D., van Rensburg L.J. et al. The lung microbiome in HIV-positive patients with active pulmonary tuberculosis. Sci. Rep. 2022;12(1):8975. DOI: 10.1038/s41598-022-12970-3.Ueckermann V., Lebre P., Geldenhuys J., Hoosien E., Cowan D., van Rensburg L.J. et al. The lung microbiome in HIV-positive patients with active pulmonary tuberculosis. Sci. Rep. 2022;12(1):8975. DOI: 10.1038/s41598-022-12970-3.Cheung M.K., Lam W.Y., Fung W.Y.W., Law P.T.W., Au C.H., Nong W. et al. Sputum microbiota in tuberculosis as revealed by 16S rRNA pyrosequencing. PLoS One. 2013;8(1):e54574. DOI: 10.1371/journal.pone.0054574.Cheung M.K., Lam W.Y., Fung W.Y.W., Law P.T.W., Au C.H., Nong W. et al. Sputum microbiota in tuberculosis as revealed by 16S rRNA pyrosequencing. PLoS One. 2013;8(1):e54574. DOI: 10.1371/journal.pone.0054574.Botero L.E., Delgado-Serrano L., Cepeda M.L., Bustos J.R., Anzola J.M., Del Portillo P. et al. Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis. Microbiome. 2014;2:29. DOI: 10.1186/2049-2618-2-29.Botero L.E., Delgado-Serrano L., Cepeda M.L., Bustos J.R., Anzola J.M., Del Portillo P. et al. Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis. Microbiome. 2014;2:29. DOI: 10.1186/2049-2618-2-29.HaileMariam M., Yu Y., Singh H., Teklu T., Wondale B., Worku A. et al. Protein and microbial biomarkers in sputum discern acute and latent tuberculosis in investigation of pastoral ethiopian cohort. Front. Cell. Infect. Microbiol. 2021;11:595554. DOI: 10.3389/fcimb.2021.595554.HaileMariam M., Yu Y., Singh H., Teklu T., Wondale B., Worku A. et al. Protein and microbial biomarkers in sputum discern acute and latent tuberculosis in investigation of pastoral ethiopian cohort. Front. Cell. Infect. Microbiol. 2021;11:595554. DOI: 10.3389/fcimb.2021.595554.Zhang M., Shen L., Zhou X., Chen H. The microbiota of human lung of pulmonary tuberculosis and the alteration caused by anti-tuberculosis drugs. Curr. Microbiol. 2022;79(11):321. DOI: 10.1007/s00284-022-03019-9.Zhang M., Shen L., Zhou X., Chen H. The microbiota of human lung of pulmonary tuberculosis and the alteration caused by anti-tuberculosis drugs. Curr. Microbiol. 2022;79(11):321. DOI: 10.1007/s00284-022-03019-9.Krishna P., Jain A., Bisen P.S. Microbiome diversity in the sputum of patients with pulmonary tuberculosis. Eur. J. Clin. Microbiol. Infect. Dis. 2016;35(7):1205–1210. DOI: 10.1007/s10096-016-2654-4.Krishna P., Jain A., Bisen P.S. Microbiome diversity in the sputum of patients with pulmonary tuberculosis. Eur. J. Clin. Microbiol. Infect. Dis. 2016;35(7):1205–1210. DOI: 10.1007/s10096-016-2654-4.Xia X., Chen J., Cheng Y., Chen F., Lu H., Liu J. et al. Comparative analysis of the lung microbiota in patients with respiratory infections, tuberculosis, and lung cancer: A preliminary study. Front. Cell. Infect. Microbiol. 2022;12:1024867. DOI: 10.3389/fcimb.2022.1024867.Xia X., Chen J., Cheng Y., Chen F., Lu H., Liu J. et al. Comparative analysis of the lung microbiota in patients with respiratory infections, tuberculosis, and lung cancer: A preliminary study. Front. Cell. Infect. Microbiol. 2022;12:1024867. DOI: 10.3389/fcimb.2022.1024867.Ticlla M.R., Hella J., Hiza H., Sasamalo M., Mhimbira F., Rutaihwa L.K. et al. The sputum microbiome in pulmonary tuberculosis and its association with disease manifestations: A cross-sectional study. Front. Microbiol. 2021;12:633396. DOI: 10.3389/fmicb.2021.633396.Ticlla M.R., Hella J., Hiza H., Sasamalo M., Mhimbira F., Rutaihwa L.K. et al. The sputum microbiome in pulmonary tuberculosis and its association with disease manifestations: A cross-sectional study. Front. Microbiol. 2021;12:633396. DOI: 10.3389/fmicb.2021.633396.Ding L., Liu Y., Wu X., Wu M., Luo X., Ouyang H. et al. Pathogen metagenomics reveals distinct lung microbiota signatures between bacteriologically confirmed and negative tuberculosis patients. Front. Cell. Infect. Microbiol. 2021;11:708827. DOI: 10.3389/fcimb.2021.708827.Ding L., Liu Y., Wu X., Wu M., Luo X., Ouyang H. et al. Pathogen metagenomics reveals distinct lung microbiota signatures between bacteriologically confirmed and negative tuberculosis patients. Front. Cell. Infect. Microbiol. 2021;11:708827. DOI: 10.3389/fcimb.2021.708827.Nakhaee M., Rezaee A., Basiri R., Soleimanpour S., Ghazvini K. Relation between lower respiratory tract microbiota and type of immune response against tuberculosis. Microb. Pathog. 2018;120:161–165. DOI: 10.1016/j.micpath.2018.04.054.Nakhaee M., Rezaee A., Basiri R., Soleimanpour S., Ghazvini K. Relation between lower respiratory tract microbiota and type of immune response against tuberculosis. Microb. Pathog. 2018;120:161–165. DOI: 10.1016/j.micpath.2018.04.054.Zhou Y., Lin F., Cui Z., Zhang X., Hu C., Shen T. et al. Correlation between either Cupriavidus or Porphyromonas and primary pulmonary tuberculosis found by analysing the microbiota in patients’ bronchoalveolar lavage fluid. PloS One. 2015;10(5):e0124194. DOI: 10.1371/journal.pone.0124194.Zhou Y., Lin F., Cui Z., Zhang X., Hu C., Shen T. et al. Correlation between either Cupriavidus or Porphyromonas and primary pulmonary tuberculosis found by analysing the microbiota in patients’ bronchoalveolar lavage fluid. PloS One. 2015;10(5):e0124194. DOI: 10.1371/journal.pone.0124194.Sala C., Benjak A., Goletti D., Banu S., Mazza-Stadler J., Jaton K. et al. Multicenter analysis of sputum microbiota in tuberculosis patients. PLoS One. 2020;15(10):e0240250. DOI: 10.1371/journal.pone.0240250.Sala C., Benjak A., Goletti D., Banu S., Mazza-Stadler J., Jaton K. et al. Multicenter analysis of sputum microbiota in tuberculosis patients. PLoS One. 2020;15(10):e0240250. DOI: 10.1371/journal.pone.0240250.Kateete D.P., Mbabazi M.M., Nakazzi F., Katabazi F.A., Kigozi E., Ssengooba W. et al. Sputum microbiota profiles of treatment-naïve TB patients in Uganda before and during first-line therapy. Sci. Rep. 2021;11(1):24486. DOI: 10.1038/s41598-021-04271-y.Kateete D.P., Mbabazi M.M., Nakazzi F., Katabazi F.A., Kigozi E., Ssengooba W. et al. Sputum microbiota profiles of treatment-naïve TB patients in Uganda before and during first-line therapy. Sci. Rep. 2021;11(1):24486. DOI: 10.1038/s41598-021-04271-y.Segal L.N., Clemente J.C., Li Y., Ruan C., Cao J., Danckers M. et al. Anaerobic bacterial fermentation products increase tuberculosis risk in antiretroviral treated HIV-patients. Cell. Host. Microbe. 2017;21(4):530–537. DOI: 10.1016/j.chom.2017.03.003.Segal L.N., Clemente J.C., Li Y., Ruan C., Cao J., Danckers M. et al. Anaerobic bacterial fermentation products increase tuberculosis risk in antiretroviral treated HIV-patients. Cell. Host. Microbe. 2017;21(4):530–537. DOI: 10.1016/j.chom.2017.03.003.Trompette A., Gollwitzer E.S., Yadava K., Sichelstiel A.K., Sprenger N., Ngom-Bru C. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 2014;2(2):159–166. DOI: 10.1038/nm.3444.Trompette A., Gollwitzer E.S., Yadava K., Sichelstiel A.K., Sprenger N., Ngom-Bru C. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 2014;2(2):159–166. DOI: 10.1038/nm.3444.Ribeiro-Rodrigues R., Resende Co T., Rojas R., Toossi Z., Dietze R., Boom W.H. et al. A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis. Clin. Exp. Immunol. 2006;144(1):25–34. DOI: 10.1111/j.1365-2249.2006.03027.x.Ribeiro-Rodrigues R., Resende Co T., Rojas R., Toossi Z., Dietze R., Boom W.H. et al. A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis. Clin. Exp. Immunol. 2006;144(1):25–34. DOI: 10.1111/j.1365-2249.2006.03027.x.Sharma P.K., Saha P.K., Singh A., Sharma S.K., Ghosh B., Mitra D.K. FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis. Am. J. Respir. Crit. Care Med. 2009;179(11):1061–1070. DOI: 10.1164/rccm.200804-529oc.Sharma P.K., Saha P.K., Singh A., Sharma S.K., Ghosh B., Mitra D.K. FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis. Am. J. Respir. Crit. Care Med. 2009;179(11):1061–1070. DOI: 10.1164/rccm.200804-529oc.Dickson R.P., Erb-Downward J.R., Freeman C.M., McCloskey L., Beck J.M., Huffnagle G.B. et al. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann. Am. Thorac. Soc. 2015;12(6):821– 830. DOI: 10.1513/annalsats.201501-029oc.Dickson R.P., Erb-Downward J.R., Freeman C.M., McCloskey L., Beck J.M., Huffnagle G.B. et al. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann. Am. Thorac. Soc. 2015;12(6):821– 830. DOI: 10.1513/annalsats.201501-029oc.Berger G., Wunderink R.G. Lung microbiota: Genuine or artifact? Isr. Med. Assoc. J. 2013;15(12):731–733.Berger G., Wunderink R.G. Lung microbiota: Genuine or artifact? Isr. Med. Assoc. J. 2013;15(12):731–733.Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Zborovskaya I. et al. Lung microbiome differentially impacts survival of patients with non-small cell lung cancer depending on tumor stroma phenotype. Biomedicines. 2020;8(9):349. DOI: 10.3390/biomedicines8090349.Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Zborovskaya I. et al. Lung microbiome differentially impacts survival of patients with non-small cell lung cancer depending on tumor stroma phenotype. Biomedicines. 2020;8(9):349. DOI: 10.3390/biomedicines8090349.Yu G., Gail M.H., Consonni D., Carugno M., Humphrys M., Pesatori A.C. et al. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome Biol. 2016;17(1):163. DOI: 10.1186/s13059-016-1021-1.Yu G., Gail M.H., Consonni D., Carugno M., Humphrys M., Pesatori A.C. et al. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome Biol. 2016;17(1):163. DOI: 10.1186/s13059-016-1021-1.Carney S.M., Clemente J.C., Cox M.J., Dickson R.P., Huang Y.J., Kitsios G.D. et al. Methods in lung microbiome research. Am. J. Respir. Cell. Mol. Biol. 2020;62(3):283–299. DOI: 10.1165/rcmb.2019-0273tr.Carney S.M., Clemente J.C., Cox M.J., Dickson R.P., Huang Y.J., Kitsios G.D. et al. Methods in lung microbiome research. Am. J. Respir. Cell. Mol. Biol. 2020;62(3):283–299. DOI: 10.1165/rcmb.2019-0273tr.Twigg H.L., Morris A., Ghedin E., Curtis J.L., Huffnagle G.B., Crothers K. et al. Use of bronchoalveolar lavage to assess the respiratory microbiome: signal in the noise. Lancet Respir. Med. 2013;1(5):354–356. DOI: 10.1016/s2213-2600(13)70117-6.Twigg H.L., Morris A., Ghedin E., Curtis J.L., Huffnagle G.B., Crothers K. et al. Use of bronchoalveolar lavage to assess the respiratory microbiome: signal in the noise. Lancet Respir. Med. 2013;1(5):354–356. DOI: 10.1016/s2213-2600(13)70117-6.Salter S.J., Cox M.J., Turek E.M., Calus S.T., Cookson W.O., Moffatt M.F. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 2014;12:87. DOI: 10.1186/s12915-014-0087-z.Salter S.J., Cox M.J., Turek E.M., Calus S.T., Cookson W.O., Moffatt M.F. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 2014;12:87. DOI: 10.1186/s12915-014-0087-z.Charlson E.S., Bittinger K., Haas A.R., Fitzgerald A.S., Frank I., Yadav A. et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am. J.Respir. Crit. Care Med. 2012;184(8):957–963. DOI: 10.1164/rccm.201104-0655oc.Charlson E.S., Bittinger K., Haas A.R., Fitzgerald A.S., Frank I., Yadav A. et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am. J.Respir. Crit. Care Med. 2012;184(8):957–963. DOI: 10.1164/rccm.201104-0655oc.Marotz C.A., Sanders J.G., Zuniga C., Zaramela L.S., Knight R., Zengler K. Improving saliva shotgun metagenomics by chemical host DNA depletion. Microbiome. 2018;6(1):42. DOI: 10.1186/s40168-018-0426-3.Marotz C.A., Sanders J.G., Zuniga C., Zaramela L.S., Knight R., Zengler K. Improving saliva shotgun metagenomics by chemical host DNA depletion. Microbiome. 2018;6(1):42. DOI: 10.1186/s40168-018-0426-3.Клименко Е.С., Погодина А.В., Рычкова Л.В., Белькова Н.Л. Возможность таксономической идентификации бифидобактерий на основании различных вариабельных районов гена 16S рРНК. Генетика. 2020;56(8):904–914. DOI: 10.31857/s001667582008007x.Клименко Е.С., Погодина А.В., Рычкова Л.В., Белькова Н.Л. Возможность таксономической идентификации бифидобактерий на основании различных вариабельных районов гена 16S рРНК. Генетика. 2020;56(8):904–914. DOI: 10.31857/s001667582008007x.Sulaiman I., Wu B.G., Li Y., Scott A.S., Malecha P., Scaglione B. et al. Evaluation of the airway microbiome in nontuberculous mycobacteria disease. Eur. Respir. J. 2018;52(4):1800810. DOI: 10.1183/13993003.00810-2018.Sulaiman I., Wu B.G., Li Y., Scott A.S., Malecha P., Scaglione B. et al. Evaluation of the airway microbiome in nontuberculous mycobacteria disease. Eur. Respir. J. 2018;52(4):1800810. DOI: 10.1183/13993003.00810-2018.Erb-Downward J.R., Thompson D.L., Han M.K., Freeman C.M., McCloskey L., Schmidt L.A. et al. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS One. 2011;6(2):e16384. DOI: 10.1371/journal.pone.0016384.Erb-Downward J.R., Thompson D.L., Han M.K., Freeman C.M., McCloskey L., Schmidt L.A. et al. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS One. 2011;6(2):e16384. DOI: 10.1371/journal.pone.0016384.

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