Chronic dust bronchitis: composition of the sputum bacterial microbiome and its association with chromosome damage in blood lymphocytes

Abstract

BACKGROUND: Recent studies show that the bacterial microbiome of the respiratory tract can influence the development of a number of diseases of the human respiratory system. Changes in the composition of the microbiome in patients are associated with dysbiosis, and in addition, many bacteria have a genotoxic potential and can directly or indirectly damage the genome in the cells of the host organism.

AIM: The aim of the study was to analyze the composition of the sputum microbiome and its relationship with chromosome damage in the blood leukocytes of patients with chronic dust bronchitis (CDB).

MATERIALS AND METHODS: The taxonomic composition of the sputum microbiome of 22 patients with CKD and 22 sputum donors from the control group was studied using next-generation sequencing (NGS) technology of 16S rRNA of bacterial genes. At the same time, the basic frequencies of chromosomal aberrations and micronuclei were determined in blood leukocytes.

RESULTS: The sputum microbiome of chronic dust bronchitis patients had a significant reduction in alpha and beta diversity parameters compared to healthy study participants. In addition, an increase in the relative abundance of the genus Streptococcus (29.97 ± 3.03 vs. 18.78 ± 2.47; p = 0.003) was found in the sputum of CP patients compared with the control. Thus, the results of metagenome sequencing indicate a common dysbiotic process with a predominance of one dominant genus of bacteria in this pulmonary pathology. The results of cytogenetic analysis of blood leukocytes showed a significant increase in the proportion of aberrant metaphases in CKD patients compared with healthy donors (3.41% vs. 1.84%; p < 0.01) and the absence of significant differences in frequency leukocytes with micronuclei between the compared groups (1.28% vs. 1.11%). Correlation analysis revealed the presence of significant direct relationships between the frequency of aberrant metaphases and the percentage of representatives of the genera Bacteroides in the sputum of patients with chronic dust bronchitis (r = 0.471; p = 0.031); Lachnoanaerobaculum (r = 0.446; p = 0.043) and Alloprevotella (r = 0.444; p = 0.044). Further studies should be devoted to the search for possible mechanisms of influence of these bacteria on clastogenic effects in the cells of the host organism.

Keywords

chronic dust bronchitis / bacterial microbiome / sputum / 16S RNA sequencing / leukocyte genome instability / chromosomal aberrations / micronuclei

References

[1] Zhdanov VF. Anti-inflammatory treatment of chronic bronchitis. Pulmonologiya. 2002;(5):102–107. (In Russ.)

[2] Жданов В.Ф. О противовоспалительном лечении хронических бронхитов // Пульмонология. 2002. № 5. С. 102–107.

[3] Fennelley KP, Stulbarg MS. Chronic bronchitis. Pulmonologiya. 1994;(2):6–13. (In Russ.)

[4] Фенелли К.П., Стулбарг М.С. Хронический бронхит // Пульмонология. 1994. № 2. С. 6–13.

[5] Bakirov AB, Mingazova SR, Karimova LK, et al. Risk of dust bronchopulmonary pathology development in workers employed in various economic brunches under impacts exerted by occupational risk factors: clinical and hygienic aspects. Health Risk Analysis. 2017;(3):83–91. (In Russ.) DOI: 10.21668/health.risk/2017.3.10

[6] Бакиров А.Б., Мингазова С.Р., Каримова Л.К., и др. Клинико-гигиенические аспекты риска развития и прогрессирования пылевой бронхолегочной патологии у работников различных отраслей экономики под воздействием производственных факторов риска // Анализ риска здоровью. 2017. № 3. С. 83–91. DOI: 10.21668/health.risk/2017.3.10

[7] Volobaev VP, Sinitsky MYu, Larionov AV, et al. Modifying influence of occupational inflammatory diseases on the level of chromosome aberrations in coal miners. Mutagenesis. 2016;31(2):225–229. DOI: 10.1093/mutage/gev080

[8] Volobaev V.P., Sinitsky M.Yu., Larionov A.V., et al. Modifying influence of occupational inflammatory diseases on the level of chromosome aberrations in coal miners // Mutagenesis. 2016. Vol. 31, No. 2. P. 225–229. DOI: 10.1093/mutage/gev080

[9] Lemercier C. When our genome is targeted by pathogenic bacteria. Cell Mol Life Sci. 2015;72(14):2665–2676. DOI: 10.1007/s00018-015-1900-8

[10] Lemercier C. When our genome is targeted by pathogenic bacteria // Cell Mol Life Sci. 2015. Vol. 72, No. 14. P. 2665–2676. DOI: 10.1007/s00018-015-1900-8

[11] Druzhinin VG, Baranova ED, Buslaev VY, et al. Bacterial DNA damage effectors in host cells. Ecological genetics. 2018;16(3):26–36. (In Russ.) DOI: 10.17816/ecogen16326-36

[12] Дружинин В.Г., Баранова Е.Д., Буслаев В.Ю., и др. Бактериальные эффекторы повреждений ДНК в клетках организма хозяина // Экологическая генетика. 2018. Т. 16, № 3. С. 26–36. DOI: 10.17816/ecogen16326-36

[13] Han MK, Huang YJ, Lipuma JJ, et al. Significance of the microbiome in obstructive lung disease. Thorax. 2012;67(5):456–463. DOI: 10.1136/thoraxjnl-2011-201183

[14] Han M.K., Huang Y.J., Lipuma J.J., et al. Significance of the microbiome in obstructive lung disease // Thorax. 2012. Vol. 67, No. 5. P. 456–463. DOI: 10.1136/thoraxjnl-2011-201183

[15] Sze MA, Dimitriu PA, Hayashi S, et al. The lung tissue microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(10):1073–1080. DOI: 10.1164/rccm.201111-2075OC

[16] Sze M.A., Dimitriu P.A., Hayashi S., et al. The lung tissue microbiome in chronic obstructive pulmonary disease // Am J Respir Crit Care Med. 2012. Vol. 185, No. 10. P. 1073–1080. DOI: 10.1164/rccm.201111-2075OC

[17] Qi Y-J, Sun X-J, Wang Z, et al. Richness of sputum microbiome in acute exacerbations of eosinophilic chronic obstructive pulmonary disease. Chin Med J (Engl). 2020;133(5):542–551. DOI: 10.1097/CM9.0000000000000677

[18] Qi Y.-J., Sun X.-J., Wang Z., et al. Richness of sputum microbiome in acute exacerbations of eosinophilic chronic obstructive pulmonary disease // Chin Med J (Engl). 2020. Vol. 133, No. 5. P. 542–551. DOI: 10.1097/CM9.0000000000000677

[19] Lin K-W, Li J, Finn PW. Emerging pathways in asthma: Innate and adaptive interactions. Biochim Biophys Acta. 2011;1810(11): 1052–1058. DOI: 10.1016/j.bbagen.2011.04.015

[20] Lin K.-W., Li J., Finn P.W. Emerging pathways in asthma: Innate and adaptive interactions // Biochim Biophys Acta. 2011. Vol. 1810, No. 11. P. 1052–1058. DOI: 10.1016/j.bbagen.2011.04.015

[21] Kozik AJ, Huang YJ. The microbiome in asthma: Role in pathogenesis, phenotype, and response to treatment. Ann Allergy Asthma Immunol. 2019;122(3):270–275. DOI: 10.1016/j.anai.2018.12.005

[22] Kozik A.J., Huang Y.J. The microbiome in asthma: Role in pathogenesis, phenotype, and response to treatment // Ann Allergy Asthma Immunol. 2019. Vol. 122, No. 3. P. 270–275. DOI: 10.1016/j.anai.2018.12.005

[23] Wootton DG, Cox MJ, Gloor GB, et al. A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease. Sci Rep. 2019;9(1):2388. DOI: 10.1038/s41598-018-38090-5

[24] Wootton D.G., Cox M.J., Gloor G.B., et al. A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease // Sci Rep. 2019. Vol. 9, No. 1. ID2388. DOI: 10.1038/s41598-018-38090-5

[25] Acosta N, Heirali A, Somayaji R, et al. Sputum microbiota is predictive of long-term clinical outcomes in young adults with cystic fibrosis. Thorax. 2018;73(11):1016–1025. DOI: 10.1136/thoraxjnl-2018-211510

[26] Acosta N., Heirali A., Somayaji R., et al. Sputum microbiota is predictive of long-term clinical outcomes in young adults with cystic fibrosis // Thorax. 2018. Vol. 73, No. 11. P. 1016–1025. DOI: 10.1136/thoraxjnl-2018-211510

[27] Hewitt RJ, Molyneaux PL. The respiratory microbiome in idiopathic pulmonary fibrosis. Ann Transl Med. 2017;5(12):250. DOI: 10.21037/atm.2017.01.56

[28] Hewitt R.J., Molyneaux P.L. The respiratory microbiome in idiopathic pulmonary fibrosis // Ann Transl Med. 2017. Vol. 5, No. 12. P. 250. DOI: 10.21037/atm.2017.01.56

[29] Maddi A, Sabharwal A, Violante T, et al. The microbiome and lung cancer. J Thorac Dis. 2019;11(1):280–291. DOI: 10.21037/jtd.2018.12.88

[30] Maddi A., Sabharwal A., Violante T., et al. The microbiome and lung cancer // J Thorac Dis. 2019. Vol. 11, No. 1. P. 280–291. DOI: 10.21037/jtd.2018.12.88

[31] Druzhinin VG, Matskova LV, Demenkov PS, et al. Genetic damage in lymphocytes of lung cancer patients is correlated to the composition of the respiratory tract microbiome. Mutagenesis. 2021;36(2):143–153. DOI: 10.1093/mutage/geab004

[32] Druzhinin V.G., Matskova L.V., Demenkov P.S., et al. Genetic damage in lymphocytes of lung cancer patients is correlated to the composition of the respiratory tract microbiome // Mutagenesis. 2021. Vol. 36, No. 2. P. 143–153. DOI: 10.1093/mutage/geab004

[33] Hungerford DA. Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl. Stain Techn. 1965;40(6):333–338. DOI: 10.3109/10520296509116440

[34] Hungerford D.A. Leukocytes cultured from small inocula of whole blood and the preparation of metaphase chromosomes by treatment with hypotonic KCl // Stain Techn. 1965. Vol. 40, No. 6. P. 333–338. DOI: 10.3109/10520296509116440

[35] Fenech M, Chang WP, Kirsch-Volders M, et al. HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res Genet Toxicol Enviton Mutag. 2003;534(1–2):65–75. DOI: 10.1016/s1383-5718(02)00249-8

[36] Fenech M., Chang W.P., Kirsch-Volders M., et al. HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures // Mutat Res Genet Toxicol Enviton Mutag. 2003. Vol. 534, No. 1–2. P. 65–75. DOI: 10.1016/s1383-5718(02)00249-8

[37] Druzhinin VG, Baranova ED, Golovina TA, et al. The baseline level of cytogenetic damage in lymphocytes and buccal epitheliocytes of lung cancer patients. Russian Journal of Genetics. 2019;55(10): 1189–1197. (In Russ.) DOI: 10.1134/S0016675819100047

[38] Дружинин В.Г., Минина В.И., Баранова Е.Д., и др. Базовый уровень цитогенетических повреждений в лимфоцитах и буккальных эпителиоцитах больных раком легкого // Генетика. 2019. Т. 55, № 10. С. 1189–1197. DOI: 10.1134/S0016675819100047

[39] Savage JR. Classification and relationships of induced chromosomal structural changes. J Med Genet. 1976;13(2):103–122. DOI: 10.1136/jmg.13.2.103

[40] Savage J.R. Classification and relationships of induced chromosomal structural changes // J Med Genet. 1976. Vol. 13, No. 2. P. 103–122. DOI: 10.1136/jmg.13.2.103

[41] Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc. 2007;2(5):1084–1104. DOI: 10.1038/nprot.2007.77

[42] Fenech M. Cytokinesis-block micronucleus cytome assay // Nat Protoc. 2007. Vol. 2, No. 5. P. 1084–1104. DOI: 10.1038/nprot.2007.77

[43] Ingel FI. Perspectives of micronuclear test in human lymphocytes cultivated in cytogenetic block conditions. Part 1: Cell proliferation. Ecological genetics. 2006;4(3):7–19. (In Russ.) DOI: 10.17816/ecogen437-19

[44] Ингель Ф.И. Перспективы использования микроядерного теста на лимфоцитах крови человека, культивируемых в условиях цитокинетического блока. Часть 1: пролиферация клеток // Экологическая генетика. 2006. Т. 4, № 3. С. 7–19. DOI: 10.17816/ecogen437-19

[45] Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME2. Nat Biotechnol. 2019;37(8):852–857. DOI: 10.1038/s41587-019-0209-9

[46] Bolyen E., Rideout J.R., Dillon M.R., et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME2 // Nat Biotechnol. 2019. Vol. 37, No. 8. P. 852–857. DOI: 10.1038/s41587-019-0209-9

[47] Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71(12):8228–8235. DOI: 10.1128/AEM.71.12.8228-8235.2005

[48] Lozupone C., Knight R. UniFrac: a new phylogenetic method for comparing microbial communities // Appl Environ Microbiol. 2005. Vol. 71, No. 12. P. 8228–8235. DOI: 10.1128/AEM.71.12.8228-8235.2005

[49] Ulker OC, Ustundag A, Duydu Y, et al. Cytogenetic monitoring of coal workers and patients with coal workers’ pneumoconiosis in Turkey. Environ Mol Mutagen. 2008;49(3):232–237. DOI: 10.1002/em.20377

[50] Ulker O.C., Ustundag A., Duydu Y., et al. Cytogenetic monitoring of coal workers and patients with coal workers’ pneumoconiosis in Turkey // Environ Mol Mutagen. 2008. Vol. 49, No. 3. P. 232–237. DOI: 10.1002/em.20377

[51] Vodicka P, Polivkova Z, Sytarova S, et al. Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls. Carcinogenesis. 2010;31(7):1238–1241. DOI: 10.1093/carcin/bgq056

[52] Vodicka P., Polivkova Z., Sytarova S., et al. Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls // Carcinogenesis. 2010. Vol. 31, No. 7. P. 1238–1241. DOI: 10.1093/carcin/bgq056

[53] Vodenkova S, Polivkova Z, Musak L, et al. Structural chromosomal aberrations as potential risk markers in incident cancer patients. Mutagenesis. 2015;30(4):557–563. DOI: 10.1093/mutage/gev018

[54] Vodenkova S., Polivkova Z., Musak L., et al. Structural chromosomal aberrations as potential risk markers in incident cancer patients // Mutagenesis. 2015. Vol. 30, No. 4. P. 557–563. DOI: 10.1093/mutage/gev018

[55] Cottliar AS, Fundia AF, Morán C, et al. Evidence of chromosome instability in chronic pancreatitis. J Exp Clin Cancer Res. 2000;19(4):513–517.

[56] Cottliar A.S., Fundia A.F., Morán C., et al. Evidence of chromosome instability in chronic pancreatitis // J Exp Clin Cancer Res. 2000. Vol. 19, No. 4. P. 513–517.

[57] Holland N, Harmatz P, Golden D, et al. Cytogenetic damage in blood lymphocytes and exfoliated epithelial cells of children with inflammatory bowel disease. Pediatr Res. 2007;61(2):209–214. DOI: 10.1203/pdr.0b013e31802d77c7

[58] Holland N., Harmatz P., Golden D., et al. Cytogenetic damage in blood lymphocytes and exfoliated epithelial cells of children with inflammatory bowel disease // Pediatr Res. 2007. Vol. 61, No. 2. P. 209–214. DOI: 10.1203/pdr.0b013e31802d77c7

[59] Chao M-R, Rossner P, Haghdoost S, et al. Nucleic acid oxidation in human health and disease. Oxid Med Cell Longev. 2013;2013:368651. DOI: 10.1155/2013/368651

[60] Chao M.-R., Rossner P., Haghdoost S., et al. Nucleic acid oxidation in human health and disease // Oxid Med Cell Longev. 2013. Vol. 2013. ID368651. DOI: 10.1155/2013/368651

[61] Druzhinin VG, Matskova LV, Fucic A. Induction and modulation of genotoxicity by the bacteriome in mammals. Mutat Res Rev Mutat Res. 2018;776:70–77. DOI: 10.1016/j.mrrev.2018.04.002

[62] Druzhinin V.G., Matskova L.V., Fucic A. Induction and modulation of genotoxicity by the bacteriome in mammals // Mutat Res Rev Mutat Res. 2018. Vol. 776. P. 70–77. DOI: 10.1016/j.mrrev.2018.04.002

[63] Xu N, Wang L, Li C, et al. (2020) Microbiota dysbiosis in lung cancer: evidence of association and potential mechanisms. Transl Lung Cancer Res. 2020;9(4):1554–1568. DOI: 10.21037/tlcr-20-156

[64] Xu N., Wang L., Li C., et al. (2020) Microbiota dysbiosis in lung cancer: evidence of association and potential mechanisms // Transl Lung Cancer Res. 2020. Vol. 9, No. 4. P. 1554–1568. DOI: 10.21037/tlcr-20-156

[65] Dickson RP, Huffnagle GB. The lung microbiome: new principles for respiratory bacteriology in health and disease. PLOS Pathog. 2015;11(7): e1004923. DOI: 10.1371/journal.ppat.1004923

[66] Dickson R.P., Huffnagle G.B. The lung microbiome: new principles for respiratory bacteriology in health and disease // PLOS Pathog. 2015. Vol. 11, No. 7. ID e1004923. DOI: 10.1371/journal.ppat.1004923

[67] Molyneaux PL, Cox MJ, Willis-Owen SAG, et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;190(8):906–913. DOI: 10.1164/rccm.201403-0541OC

[68] Molyneaux P.L., Cox M.J., Willis-Owen S.A.G., et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis // Am J Respir Crit Care Med. 2014. Vol. 190, No. 8. P. 906–913. DOI: 10.1164/rccm.201403-0541OC

[69] Han MK, Zhou Y, Murray S, et al. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. Lancet Respir Med. 2014;2(7):548–556. DOI: 10.1016/S2213-2600(14)70069-4

[70] Han M.K., Zhou Y., Murray S., et al. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study // Lancet Respir Med. 2014. Vol. 2, No. 7. P. 548–556. DOI: 10.1016/S2213-2600(14)70069-4

[71] Cameron SJS, Lewis KE, Huws SA, et al. A pilot study using metagenomic sequencing of the sputum microbiome suggests potential bacterial biomarkers for lung cancer. PLoS One. 2017;12(5): e0177062. DOI: 10.1371/journal.pone.0177062

[72] Cameron S.J.S., Lewis K.E., Huws S.A., et al. A pilot study using metagenomic sequencing of the sputum microbiome suggests potential bacterial biomarkers for lung cancer // PLoS One. 2017. Vol. 12, No. 5. ID e0177062. DOI: 10.1371/journal.pone.0177062

[73] Hosgood HD III, Sapkota AR, Rothman N, et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures. Environ Mol Mutagen. 2014;55(8):643–651. DOI: 10.1002/em.21878

[74] Hosgood H.D. III, Sapkota A.R., Rothman N., et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures // Environ Mol Mutagen. 2014. Vol. 55, No. 8. P. 643–651. DOI: 10.1002/em.21878

[75] Bello S, Vengoechea JJ, Ponce-Alonso M, et al. Core microbiota in central lung cancer with streptococcal enrichment as a possible diagnostic marker. Archivos de Bronconeumol. (Engl Ed). 2020;57(11):681–689. DOI: 10.1016/j.arbres.2020.05.034

[76] Bello S., Vengoechea J.J., Ponce-Alonso M., et al. Core microbiota in central lung cancer with streptococcal enrichment as a possible diagnostic marker // Archivos de Bronconeumol. (Engl Ed). 2020. Vol. 57, No. 11. P. 681–689. DOI: 10.1016/j.arbres.2020.05.034

[77] Pragman AA, Kim HB, Reilly CS, et al. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 2012;7(10): e47305. DOI: 10.1371/journal.pone.0047305

[78] Pragman A.A., Kim H.B., Reilly C.S., et al. The lung microbiome in moderate and severe chronic obstructive pulmonary disease // PLoS One. 2012. Vol. 7, No. 10. ID e47305. DOI: 10.1371/journal.pone.0047305

[79] Einarsson GG, Comer DM, McIlreavey L, et al. Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers. Thorax. 2016;71(9):795–803. DOI: 10.1136/thoraxjnl-2015-207235

[80] Einarsson G.G., Comer D.M., McIlreavey L., et al. Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers // Thorax. 2016. Vol. 71, No. 9. P. 795–803. DOI: 10.1136/thoraxjnl-2015-207235

[81] Haldar K, George L, Wang Z, et al. The sputum microbiome is distinct between COPD and health, independent of smoking history. Respir Res. 2020;21(1):183. DOI: 10.1186/s12931-020-01448-3

[82] Haldar K., George L., Wang Z., et al. The sputum microbiome is distinct between COPD and health, independent of smoking history // Respir Res. 2020. Vol. 21, No. 1. ID183. DOI: 10.1186/s12931-020-01448-3

[83] Wang Z, Liu H, Wang F, et al. A refined view of airway microbiome in chronic obstructive pulmonary disease at species and strain-levels. Front Microbiol. 2020;11:1758. DOI: 10.3389/fmicb.2020.01758

[84] Wang Z., Liu H., Wang F., et al. A refined view of airway microbiome in chronic obstructive pulmonary disease at species and strain-levels // Front Microbiol. 2020. Vol. 11. ID 1758. DOI: 10.3389/fmicb.2020.01758

[85] Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev. 2009;22(2):349–369. DOI:10.1128/CMR.00053-08

[86] Sears C.L. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes // Clin Microbiol Rev. 2009. Vol. 22, No. 2. P. 349–369. DOI:10.1128/CMR.00053-08

[87] Goodwin AC, Destefano Shields CE, Wu S, et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. PNAS. 2011;108(37):15354–15359. DOI: 10.1073/pnas.1010203108

[88] Goodwin A.C., Destefano Shields C.E., Wu S., et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis // PNAS. 2011. Vol. 108, No. 37. P. 15354–15359. DOI: 10.1073/pnas.1010203108

[89] Allen J, Rosendahl Huber A, Pleguezuelos-Manzano C, et al. Colon tumors in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice do not display a unique mutational signature but instead possess host-dependent alterations in the APC gene. Microbiol Spectr. 2022;10(3): e0105522. DOI: 10.1128/spectrum.01055-22

[90] Allen J., Rosendahl Huber A., Pleguezuelos-Manzano C., et al. Colon Tumors in Enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice do not display a unique mutational signature but instead possess host-dependent alterations in the APC gene // Microbiol Spectr. 2022. Vol. 10, No. 3. ID e0105522. DOI: 10.1128/spectrum.01055-22

Funding

Российский научный фондRussian Science Foundation(18-14-00022п)

RIGHTS & PERMISSIONS

Eco-Vector