Abstract
Gut microbiota, especially human pathogens, has been shown to be involved in the occurrence and development of cancer. Esophageal squamous cell carcinoma and lung cancer are two malignant cancers, and their relationship with gut microbiota is still unclear. Virulence factor database (VFDB) is an integrated and comprehensive online resource for curating information about human pathogens. Here, based on VFDB database, we analyzed the differences of bacteria at genus level in the gut of patients with esophageal squamous cell carcinoma, lung cancer, and healthy controls. We proposed the possible cancer-associated bacteria in gut and put forward their possible effects. Apart from this, principal coordinate analysis (PCoA) and analysis of similarities (ANSOIM) suggested that some bacteria in the gut can be used as potential biomarkers to screen esophageal squamous cell carcinoma and lung cancer, and their effectiveness was preliminary verified. The relative abundance of Klebsiella and Streptococcus can be used to distinguish patients with esophageal squamous cell carcinoma and lung cancer from healthy controls. The absolute abundance of Klebsiella can further distinguish patients with esophageal squamous cell carcinoma from patients with lung cancer. In particular, the relative abundance of Fusobacterium can directly distinguish between patients with esophageal squamous cell carcinoma and healthy controls. Additionally, the absolute abundance of Haemophilus can distinguish lung cancer from healthy controls. Our study provided a new way based on VFDB database to explore the relationship between gut microbiota and cancer, and initially proposed a feasible cancer screening method.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnold M, Soerjomataram I, Ferlay J, Forman D (2015) Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64:381–387. https://doi.org/10.1136/gutjnl-2014-308124
Arthur JC et al (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338(6103):120–3. https://doi.org/10.1126/science.1224820
Baba Y, Iwatsuki M, Yoshida N, Watanabe M, Baba H (2017) Review of the gut microbiome and esophageal cancer: pathogenesis and potential clinical implications. Ann Gastroenterol Surg 1:99–104. https://doi.org/10.1002/ags3.12014
Chang MC et al (2018) Butyrate stimulates histone H3 acetylation, 8-isoprostane production, RANKL expression, and regulated osteoprotegerin expression/secretion in MG-63 osteoblastic cells. Int J Mol Sci 19:4071. https://doi.org/10.3390/ijms19124071
Cheng M et al (2014) Microbiota modulate tumoral immune surveillance in lung through a T17 immune cell-dependent mechanism. Cancer Res 74:4030–4041. https://doi.org/10.1158/0008-5472.CAN-13-2462
Cheng WT, Kantilal HK, Davamani F (2020) The mechanism of Bacteroides fragilis toxin contributes to colon cancer formation. Malays J Med Sci 27(4):9–21. https://doi.org/10.21315/mjms2020.27.4.2
Erdman SE, Poutahidis T (2015) Gut bacteria and cancer. Biochim Biophys Acta (BBA) 1856:86–90. https://doi.org/10.1016/j.bbcan.2015.05.007
Fenneman AC, Rampanelli E, Yin YS, Ames J, Blaser MJ, Fliers E, Nieuwdorp M (2020) Gut microbiota and metabolites in the pathogenesis of endocrine disease. Biochem Soc Trans 48:915–931. https://doi.org/10.1042/BST20190686
Goedert JJ et al (2015) Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. JNCI. https://doi.org/10.1093/jnci/djv147
He Z et al (2019) Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut 68:289–300. https://doi.org/10.1136/gutjnl-2018-317200
Huck O, Al-Hashemi J, Poidevin L, Poch O, Davideau JL, Tenenbaum H, Amar S (2017) Identification and characterization of MicroRNA differentially expressed in macrophages exposed to Porphyromonas gingivalis infection. Infect Immun 85:e00771-16. https://doi.org/10.1128/IAI.00771-16
Huston JR et al (2000) Redefined duplex ultrasonographic criteria for diagnosis of carotid artery stenosis. Mayo Clin Proc 75:1133–1140. https://doi.org/10.4065/75.11.1133
Huycke MM, Abrams V, Moore DR (2002) Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23:529–536. https://doi.org/10.1093/carcin/23.3.529
Kaur CP, Vadivelu J, Chandramathi S (2018) Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases. J Dig Dis 19:262–271. https://doi.org/10.1111/1751-2980.12595
Khan Z, Siddiqui N, Saif MW (2018) Enterococcus faecalis infective endocarditis and colorectal carcinoma: case of new association gaining ground. Gastroenterol Res 11:238–240. https://doi.org/10.14740/gr996w
Kim JY, Lee J-L (2014) Multipurpose assessment for the quantification of Vibrio spp. and total bacteria in fish and seawater using multiplex real-time polymerase chain reaction. J Sci Food Agric 94:2807–2817. https://doi.org/10.1002/jsfa.6699
Li Y et al (2020) Age-related shifts in gut microbiota contribute to cognitive decline in aged rats. Aging (Albany NY) 12:7801–7817. https://doi.org/10.18632/aging.103093
Liang Q et al (2017) Fecal bacteria act as novel biomarkers for noninvasive diagnosis of colorectal cancer. Clin Cancer Res 23:2061–2070. https://doi.org/10.1158/1078-0432.CCR-16-1599
Liu B, Zheng D, Jin Q, Chen L, Yang J (2019) VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res 47:D687–D692. https://doi.org/10.1093/nar/gky1080
Liu F et al (2019) Dysbiosis of the gut microbiome is associated with tumor biomarkers in lung cancer. Int J Biol Sci 15:2381–2392. https://doi.org/10.7150/ijbs.35980
Lu L, Wu Y, Zuo L, Luo X, Large PJ (2014) Intestinal microbiome and digoxin inactivation: meal plan for digoxin users? World J Microbiol Biotechnol 30:791–799. https://doi.org/10.1007/s11274-013-1507-x
Lu MC et al (2017) Colibactin contributes to the hypervirulence of pks(+) K1 CC23 Klebsiella pneumoniae in mouse meningitis infections. Front Cell Infect Microbiol 7:103. https://doi.org/10.3389/fcimb.2017.00103
Matos R et al (2021) Adhesion of Helicobacter species to the human gastric mucosa: a deep look into glycans role. Front Mol Biosci 8:656439. https://doi.org/10.3389/fmolb.2021.656439
Mejia R et al (2020) Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study. Parasit Vectors 13:200. https://doi.org/10.1186/s13071-020-04073-7
Meng C, Bai C, Brown TD, Hood LE, Tian Q (2018) Human gut microbiota and gastrointestinal cancer. Genomics Proteomics Bioinform 16:33–49. https://doi.org/10.1016/j.gpb.2017.06.002
Oehmcke-Hecht S, Mandl V, Naatz LT, Duhring L, Kohler J, Kreikemeyer B, Maletzki C (2020) Streptococcus gallolyticus abrogates anti-carcinogenic properties of tannic acid on low-passage colorectal carcinomas. Sci Rep 10:4714. https://doi.org/10.1038/s41598-020-61458-5
Pere-Vedrenne C et al (2017) The cytolethal distending toxin subunit CdtB of Helicobacter hepaticus promotes senescence and endoreplication in xenograft mouse models of hepatic and intestinal cell lines. Front Cell Infect Microbiol 7:268. https://doi.org/10.3389/fcimb.2017.00268
Pushalkar S et al (2018) The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 8:403–416. https://doi.org/10.1158/2159-8290.CD-17-1134
Qin N et al (2014) Alterations of the human gut microbiome in liver cirrhosis. Nature 513:59–64. https://doi.org/10.1038/nature13568
Ren Z et al (2017) Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China. Oncotarget 8:95176–95191. https://doi.org/10.18632/oncotarget.18820
Rezasoltani S et al (2018) Applying simple linear combination, multiple logistic and factor analysis methods for candidate fecal bacteria as novel biomarkers for early detection of adenomatous polyps and colon cancer. J Microbiol Methods 155:82–88. https://doi.org/10.1016/j.mimet.2018.11.00
Risch HA, Yu H, Lu L, Kidd MS (2010) ABO blood group, Helicobacter pylori seropositivity and risk of pancreatic cancer: a case-control study. J Natl Cancer Inst 102:502–505. https://doi.org/10.1093/jnci/djq007
Risch HA, Lu L, Kidd MS, Wang J, Zhang W, Ni Q, Gao YT, Yu H (2014) Helicobacter pylori seropositivities and risk of pancreatic carcinoma. Cancer Epidemiol Biomark Prev 23:172–178. https://doi.org/10.1158/1055-9965.EPI-13-0447
Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, Tuohy K (2018) Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr 57:1–24. https://doi.org/10.1007/s00394-017-1445-8
Schulz MD et al (2014) High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature 514:508–512. https://doi.org/10.1038/nature13398
Sender R, Fuchs S, Milo R (2016) Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:337–340. https://doi.org/10.1016/j.cell.2016.01.013
Shin NR, Whon TW, Bae JW (2015) Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 33:496–503. https://doi.org/10.1016/j.tibtech.2015.06.011
Wang Y et al (2019) L. pseudomesenteroides and L. johnsonii isolated from yaks in Tibet modulate gut microbiota in mice to ameliorate enteroinvasive Escherichia coli-induced diarrhea. Microb Pathog 132:1–9. https://doi.org/10.1016/j.micpath.2019.04.020
Wilson MR et al (2019) The human gut bacterial genotoxin colibactin alkylates DNA. Science 363:eaar7785. https://doi.org/10.1126/science.aar7785
Wong SH, Kwong TNY, Wu CY, Yu J (2019) Clinical applications of gut microbiota in cancer biology. Semin Cancer Biol 55:28–36. https://doi.org/10.1016/j.semcancer.2018.05.003
Wu S, Morin PJ, Maouyo D, Sears CL (2003) Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology 124:392–400. https://doi.org/10.1053/gast.2003.50047
Yan L, Liu D, Wang XH, Wang Y, Zhang B, Wang M, Xu H (2017) Bacterial plasmid-mediated quinolone resistance genes in aquatic environments in China. Sci Rep 7:40610. https://doi.org/10.1038/srep40610
Yang T, Zeng CW, Zheng R, Zhang Y, Li Z, Qi J, Wnag M, Chen T, Lou J, Lu L, Zhou T, Dai S, Cai M, You W, Pan K (2016) Helicobacter pylori infection, H19 and LINC00152 expression in serum and risk of gastric cancer in a Chinese population. Cancer Epidemiol 44:147–153. https://doi.org/10.1016/j.canep.2016.08.015
Yang TW et al (2019) Enterotype-based analysis of gut microbiota along the conventional adenoma-carcinoma colorectal cancer pathway. Sci Rep 9:10923. https://doi.org/10.1038/s41598-019-45588-z
Youden WJ (1950) Index for rating diagnostic tests. Cancer 3:32–35. https://doi.org/10.1002/1097-0142(1950)3:1%3c32:aid-cncr2820030106%3e3.0.co;2-3
Zheng Y et al (2020) Specific gut microbiome signature predicts the early-stage lung cancer. Gut Microbes 11:1–13. https://doi.org/10.1080/19490976.2020.1737487
Zhu G, Su H, Johnson CH, Khan SA, Kluger H, Lu L (2021) Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma. Eur J Cancer 161:25–34. https://doi.org/10.1016/j.ejca.2021.03.053
Acknowledgements
We thank Eno Ernest Essien, for editing the English text of a draft of this manuscript. This study was funded by National Natural Science Foundation of China grants (81872579, 81573108, and 81172747) and New Century Excellent Talents in University from Ministry of Education (NCET-13-012).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All the authors declare no conflict of interests.
Ethical approval
The protocol was approved by the ethics committee of Zhongda Hospital of Southeast University.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Shen, W., Tang, D., Deng, Y. et al. Association of gut microbiomes with lung and esophageal cancer: a pilot study. World J Microbiol Biotechnol 37, 128 (2021). https://doi.org/10.1007/s11274-021-03086-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11274-021-03086-3