Preview

Vavilov Journal of Genetics and Breeding

Advanced search

Composition of the sputum bacterial microbiome of patients with different pathomorphological forms of non-small-cell lung cancer

https://doi.org/10.18699/vjgb-24-25

Abstract

Recent studies have shown that the bacterial microbiome of the respiratory tract influences the development of lung cancer. Changes in the composition of the microbiome are observed in patients with chronic inflammatory processes. Such microbiome changes may include the occurrence of bacteria that cause oxidative stress and that are capable of causing genome damage in the cells of the host organism directly and indirectly. To date, the composition of the respiratory microbiome in patients with various histological variants of lung cancer has not been studied. In the present study, we determined the taxonomic composition of the sputum microbiome of 52 patients with squamous cell carcinoma of the lung, 52 patients with lung adenocarcinoma and 52 healthy control donors, using next-generation sequencing (NGS) on the V3-V4 region of the bacterial gene encoding 16S rRNA. The sputum microbiomes of patients with different histological types of lung cancer and controls did not show significant differences in terms of the species richness index (Shannon); however, the patients differed from the controls in terms of evenness index (Pielou). The structures of bacterial communities (beta diversity) in the adenocarcinoma and squamous cell carcinoma groups were also similar; however, when analyzed according to the matrix constructed by the Bray–Curtis method, there were differences between patients with squamous cell carcinoma and healthy subjects, but not between those with adenocarcinoma and controls. Using the LEFse method it was possible to identify an increase in the content of Bacillota (Streptococcus and Bacillus) and Actinomycetota (Rothia) in the sputum of patients with squamous cell carcinoma when compared with samples from patients with adenocarcinoma. There were no differences in the content of bacteria between the samples of patients with adenocarcinoma and the control ones. The content of representatives of the genera Streptococcus, Bacillus, Peptostreptococcus (phylum Bacillota), Prevotella, Macellibacteroides (phylum Bacteroidota), Rothia (phylum Actinomycetota) and Actinobacillus (phylum Pseudomonadota) was increased in the microbiome of sputum samples from patients with squamous cell carcinoma, compared with the control. Thus, the sputum bacterial microbiome of patients with different histological types of non-small-cell lung cancer has significant differences. Further research should be devoted to the search for microbiome biomarkers of lung cancer at the level of bacterial species using whole-genome sequencing.

About the Authors

V. G. Druzhinin
Kemerovo State University; Kemerovo State Medical University
Russian Federation

Kemerovo



E. D. Baranova
Kemerovo State University
Russian Federation

Kemerovo



P. S. Demenkov
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation

Novosibirsk



L. V. Matskova
Karolinska Institute
Sweden

Stockholm



A. V. Larionov
Kemerovo State University
Russian Federation

Kemerovo



References

1. Bolyen E., Rideout J.R., Dillon M.R., Bokulich N.A., Abnet C.C., AlGhalith G.A., Alexander H., … Willis A.D., Xu Z.Z., Zaneveld J.R., Zhang Y., Zhu Q., Knight R., Caporaso J.G. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 2019;37(8):852-857. DOI 10.1038/s41587-019-0209-9

2. Cameron S.J.S., Lewis K.E., Huws S.A., Hegarty M.J., Lewis P.D., Pachebat J.A., Mur L.A.J. 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

3. Chen Y., Wu F.H., Wu P.Q., Xing H.Y., Ma T. The role of the tumor microbiome in tumor development and its treatment. Front. Immunol. 2022;13:935846. DOI 10.3389/fimmu.2022.935846

4. Cheng C., Wang Z., Wang J., Ding C., Sun C., Liu P., Xu X., Liu Y., Chen B., Gu B. Characterization of the lung microbiome and exploration of potential bacterial biomarkers for lung cancer. Transl. Lung. Cancer Res. 2020;9(3):693-704. DOI 10.21037/tlcr-19-590

5. Cheng T.Y., Cramb S.M., Baade P.D., Youlden D.R., Nwogu C., Reid M.E. The international epidemiology of lung cancer: latest trends, disparities, and tumor characteristics. J. Thorac. Oncol. 2016; 11(10):1653-1671. DOI 10.1016/j.jtho.2016.05.021

6. Chiu C.Y., Miller S.A. Clinical metagenomics. Nat. Rev. Genet. 2019; 20(6):341-355. DOI 10.1038/s41576-019-0113-7

7. Costello E.K., Stagaman K., Dethlefsen L., Bohannan B.J., Relman D.A. The application of ecological theory toward an understanding of the human microbiome. Science. 2012;336(6086):12551262. DOI 10.1126/science.1224203

8. Druzhinin V.G., Matskova L.V., Demenkov P.S., Baranova E.D., Volobaev V.P., Minina V.I., Apalko S.V., Churina M.A., Romanyuk S.A., Shcherbak S.G., Ivanov V.I., Larionov A.V. Taxonomic diversity of sputum microbiome in lung cancer patients and its relationship with chromosomal aberrations in blood lymphocytes. Sci. Rep. 2020; 10(1):9681. DOI 10.1038/s41598-020-66654-x

9. Druzhinin V.G., Matskova L.V., Demenkov P.S., Baranova E.D., Volobaev V.P., Minina V.I., Larionov A.V., Titov V.A., Fucic A. 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

10. Goldstraw P. New staging system: How does it affect our practice? J. Clin. Oncol. 2013;31(8):984-991. DOI 10.1200/JCO.2012.42.7922

11. Gomes S., Cavadas B., Ferreira J.C., Marques P.I., Monteiro C., Sucena M., Sousa C., Vaz Rodrigues L., Teixeira G., Pinto P., Tavares de Abreu T., Bárbara C., Semedo J., Mota L., Carvalho A.S., Matthiesen R., Pereira L., Seixas S. Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. Sci. Rep. 2019;9(1):12838. DOI 10.1038/s41598-019-49195-w

12. Haldar K., George L., Wang Z., Mistry V., Ramsheh M.Y., Free R.C., John C., Reeve N.F., Miller B.E., Tal-Singer R., Webb A.J., Brookes A.J., Tobin M.D., Singh D., Donaldson G.C., Wedzicha J.A., Brown J.R., Barer M.R., Brightling C.E. The sputum microbiome is distinct between COPD and health, independent of smoking history. Respir. Res. 2020;21(1):183. DOI 10.1186/s12931020-01448-3

13. Hasegawa A., Sato T., Hoshikawa Y., Ishida N., Tanda N., Kawamura Y., Kondo T., Takahashi N. Detection and identification of oral anaerobes in intraoperative bronchial fluids of patients with pulmonary carcinoma. Microbiol. Immunol. 2014;58(7):375-381. DOI 10.1111/1348-0421.12157

14. Herbst R.S., Heymach J.V., Lippman S.M. Lung cancer. N. Engl. J. Med. 2008;359(13):1367-1380. DOI 10.1056/NEJMra0802714

15. Hosgood H.D. 3rd, Sapkota A.R., Rothman N., Rohan T., Hu W., Xu J., Vermeulen R., He X., White J.R., Wu G., Wei F., Mongodin E.F., Lan Q. 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

16. Hosgood H.D. 3rd, Mongodin E.F., Wan Y., Hua X., Rothman N., Hu W., Vermeulen R., Seow W.J., Rohan T., Xu J., Li J., He J., Huang Y., Yang K., Wu G., Wei F., Shi J., Sapkota A.R., Lan Q. The respiratory tract microbiome and its relationship to lung cancer and environmental exposures found in rural China. Environ. Mol. Mutagen. 2019;60(7):617-623. DOI 10.1002/em.22291

17. Huang C., Shi G. Smoking and microbiome in oral, airway, gut and some systemic diseases. J. Transl. Med. 2019;17(1):225. DOI 10.1186/s12967-019-1971-7

18. Huang D., Su X., Yuan M., Zhang S., He J., Deng Q., Qiu W., Dong H., Cai S. The characterization of lung microbiome in lung cancer patients with different clinicopathology. Am. J. Cancer Res. 2019;9(9): 2047-2063

19. Kim O.H., Choi B.Y., Kim D.K., Kim N.H., Rho J.K., Sul W.J., Lee S.W. The microbiome of lung cancer tissue and its association with pathological and clinical parameters. Am. J. Cancer. Res. 2022;12(5):2350-2362

20. Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Zborovskaya I., Mochalnikova V., Kataev V., Khlopko Y., Plot nikov A., Gratchev A. 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

21. Lee S.H., Sung J.Y., Yong D., Chun J., Kim S.Y., Song J.H., Chung K.S., Kim E.Y., Jung J.Y., Kang Y.A., Kim Y.S., Kim S.K., Chang J., Park M.S. Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions. Lung Cancer. 2016;102:89-95. DOI 10.1016/j.lungcan.2016.10.016

22. Leng Q., Holden V.K., Deepak J., Todd N.W., Jiang F. Microbiota biomarkers for lung cancer. Diagnostics (Basel). 2021;11(3):407. DOI 10.3390/diagnostics11030407

23. Liu H.X., Tao L.L., Zhang J., Zhu Y.G., Zheng Y., Liu D., Zhou M., Ke H., Shi M.M., Qu J.M. Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects. Int. J. Cancer. 2018;142(4):769-778. DOI 10.1002/ijc.31098

24. Liu N.N., Ma Q., Ge Y., Yi C.X., Wei L.Q., Tan J.C., Chu Q., Li J.Q., Zhang P., Wang H. Microbiome dysbiosis in lung cancer: from composition to therapy. NPJ Precis. Oncol. 2020;4(1):33. DOI 10.1038/s41698-020-00138-z

25. 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

26. Maddi A., Sabharwal A., Violante T., Manuballa S., Genco R., Patnaik S., Yendamuri S. The microbiome and lung cancer. J. Thorac. Dis. 2019;11(1):280-291. DOI 10.21037/jtd.2018.12.88

27. Mao Q., Jiang F., Yin R., Wang J., Xia W., Dong G., Ma W., Yang Y., Xu L., Hu J. Interplay between the lung microbiome and lung cancer. Cancer Lett. 2018;415:40-48. DOI 10.1016/j.canlet.2017.11.036

28. Molina J.R., Yang P., Cassivi S.D., Schild S.E., Adjei A.A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin. Proc. 2008;83(5):584-94. DOI 10.4065/83.5.584

29. Parte A.C., Sardà Carbasse J., Meier-Kolthoff J.P., Reimer L.C., Göker M. List of Prokaryotic names with Standing in Nomenclature (LPSN) moves to the DSMZ. Int. J. Syst. Evol. Microbiol. 2020; 70(11):5607-5612. DOI 10.1099/ijsem.0.004332

30. Peters B.A., Hayes R.B., Goparaju C., Reid C., Pass H.I., Ahn J. The microbiome in lung cancer tissue and recurrence-free survival. Cancer Epidemiol. Biomark. Prev. 2019;28(4):731-740. DOI 10.1158/1055-9965.EPI-18-0966

31. Ran Z., Liu J., Wang F., Xin C., Shen X., Zeng S., Song Z., Xiong B. Analysis of pulmonary microbial diversity in patients with advanced lung cancer based on high-throughput sequencing technology. Zhongguo Fei Ai Za Zhi. 2020;23(12):1031-1038. DOI 10.3779/j.issn.1009-3419.2020.103.16 (in Chinese)

32. Segata N., Izard J., Waldron L., Gevers D., Miropolsky L., Garrett W.S., Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60. DOI 10.1186/gb-2011-12-6-r60

33. Shanahan E.R., Shah A., Koloski N., Walker M.M., Talley N.J., Morrison M., Holtmann G.J. Influence of cigarette smoking on the human duodenal mucosa-associated microbiota. Microbiome. 2018;6(1): 150. DOI 10.1186/s40168-018-0531-3

34. Tsao M.S., Yoon J.Y. The eighth TNM classification for lung cancer – What is next? Lung Cancer. 2018;121:97-98. DOI 10.1016/j.lungcan.2018.04.018

35. Tsay J.J., Wu B.G., Badri M.H., Clemente J.C., Shen N., Meyn P., Li Y., Yie T.A., Lhakhang T., Olsen E., Murthy V., Michaud G., Sulaiman I., Tsirigos A., Heguy A., Pass H., Weiden M.D., Rom W.N., Sterman D.H., Bonneau R., Blaser M.J., Segal L.N. Airway mcrobiota is associated with upregulation of the PI3K pathway in lung cancer. Am. J. Respir. Crit. Care. Med. 2018;198:1188-1198. DOI 10.1164/rccm.201710-2118OC

36. Wang K., Huang Y., Zhang Z., Liao J., Ding Y., Fang X., Liu L., Luo J., Kong J. A preliminary study of microbiota diversity in saliva and bronchoalveolar lavage fluid from patients with primary bronchogenic carcinoma. Med. Sci. Monit. 2019;25:2819-2834. DOI 10.12659/MSM.915332

37. Wu Y., Jiao N., Zhu R., Zhang Y., Wu D., Wang A.J., Fang S., Tao L., Li Y., Cheng S., He X., Lan P., Tian C., Liu N.N., Zhu L. Identification of microbial markers across populations in early detection of colorectal cancer. Nat. Commun. 2021;12(1):3063. DOI 10.1038/s41467-021-23265-y

38. Xavier J.B., Young V.B., Skufca J., Ginty F., Testerman T., Pearson A.T., Macklin P., … Johnson W.E., Jobin C., Ridlon J.M., Koh A.Y., Yu M., Kelly L., Wargo J.A. The cancer microbiome: distinguishing direct and indirect effects requires a systemic view. Trends Cancer. 2020;6(3):192-204. DOI 10.1016/j.trecan.2020.01.004

39. Yagi K., Huffnagle G.B., Lukacs N.W., Asai N. The lung microbiome during health and disease. Int. J. Mol. Sci. 2021;22(19):10872. DOI 10.3390/ijms221910872

40. Yan X., Yang M., Liu J., Gao R., Hu J., Li J., Zhang L., Shi Y., Guo H., Cheng J., Razi M., Pang S., Yu X., Hu S. Discovery and validation of potential bacterial biomarkers for lung cancer. Am. J. Cancer Res. 2015;5(10):3111-3122

41. Ying K.L., Brasky T.M., Freudenheim J.L., McElroy J.P., Nickerson Q.A., Song M.A., Weng D.Y., Wewers M.D., Whiteman N.B., Mathe E.A., Shields P.G. Saliva and lung microbiome associations with electronic cigarette use and smoking. Cancer Prev. Res. ( Phila). 2022;15(7):435-446. DOI 10.1158/1940-6207.CAPR-21-0601

42. Zhang W., Luo J., Dong X., Zhao S., Hao Y., Peng C., Shi H., Zhou Y., Shan L., Sun Q., Li Y., Zhao X. Salivary microbial dysbiosis is associated with systemic inflammatory markers and predicted oral metabolites in non-small cell lung cancer patients. J. Cancer. 2019; 10(7):1651-1662. DOI 10.7150/jca.28077

43. Zheng L., Sun R., Zhu Y., Li Z., She X., Jian X., Yu F., Deng X., Sai B., Wang L., Zhou W., Wu M., Li G., Tang J., Jia W., Xiang J. Lung microbiome alterations in NSCLC patients. Sci. Rep. 2021;11(1): 11736. DOI 10.1038/s41598-021-91195-2

44. Zhuo M., An T., Zhang C., Wang Z. Characterization of microbiota in cancerous lung and the contralateral non-cancerous lung within lung cancer patients. Front. Oncol. 2020;10:1584. DOI 10.3389/fonc.2020.01584


Review

Views: 561


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2500-3259 (Online)