Skip to main content

Advertisement

SpringerLink
Log in

Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation

  • Original Paper
  • Published:
Archives of Microbiology Aims and scope Submit manuscript

Abstract

Advanced combinatorial treatments of surgery, chemotherapy, and radiotherapy do not have any effect on the enhancement of a 5-year survival rate of oral squamous cell carcinoma (OSCC). The discovery of early diagnostic non-invasive biomarkers is required to improve the survival rate of OSCC patients. Recently, it has been reported that oral microbiome has a significant contribution to the development of OSCC. Oral microbiome induces inflammatory response through the production of cytokines and chemokines that enhances tumor cell proliferation and survival. The study aims to develop saliva-based oral microbiome and cytokine biomarker panel that screen OSCC patients based on the level of the microbiome and cytokine differences. We compared the oral microbiome signatures and cytokine level in the saliva of OSCC patients and healthy individuals by 16S rRNA gene sequencing targeting the V3/V4 region using the MiSeq platform and cytokine assay, respectively. The higher abundance of Prevotella melaninogenica, Fusobacterium sp., Veillonella parvula, Porphyromonas endodontalis, Prevotella pallens, Dialister, Streptococcus anginosus, Prevotella nigrescens, Campylobacter ureolyticus, Prevotella nanceiensis, Peptostreptococcus anaerobius and significant elevation of IL-8, IL-6, TNF-α, GM-CSF, and IFN-γ in the saliva of patients having OSCC. Oncobacteria such as S. anginosus, V. parvula, P. endodontalis, and P. anaerobius may contribute to the development of OSCC by increasing inflammation via increased expression of inflammatory cytokines such as IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF. These oncobacteria and cytokines panels could potentially be used as a non-invasive biomarker in clinical practice for more efficient screening and early detection of OSCC patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, Gamonal J, Diaz PI (2013) The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J 7(5):1016–1025. https://doi.org/10.1038/ismej.2012.174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Hebshi NN, Nasher AT, Maryoud MY, Homeida HE, Chen T, Idris AM, Johnson NW (2017) Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma. Sci Rep 7(1):1834

    PubMed  PubMed Central  Google Scholar 

  • Amer A, Galvin S, Healy CM, Moran GP (2017) The microbiome of potentially malignant oral leukoplakia exhibits enrichment for Fusobacterium, Leptotrichia, Campylobacter, and Rothia species. Front Microbiol 8:2391

    PubMed  PubMed Central  Google Scholar 

  • Andrews S (2010) FastQC: A quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk?/projects/fastqc/. Accessed 2011 Oct 6

  • Aronesty E (2013) TOBioiJ: comparison of sequencing utility programs. https://doi.org/10.2174/1875036201307010001. https://code.google.com/archive/p/ea-utils/

  • Bagaitkar J, Demuth DR, Scott DA (2008) Tobacco use increases susceptibility to bacterial infection. Tob Induc Dis 4:12

    PubMed  PubMed Central  Google Scholar 

  • Began J, Sarrion G, Jimenez Y (2010) Oral cancer: clinical features. Oral Oncol 46:414–417

    Google Scholar 

  • Bertelsen A, Elborn JS, Schock BC (2019) Infection with Prevotella nigrescens induces TLR2 signalling and low levels of p65 mediated inflammation in Cystic Fibrosis bronchial epithelial cells. J Cyst Fibros 19:211–218

    PubMed  Google Scholar 

  • Börnigen D, Ren B, Pickard R, Li J, Ozer E, Hartmann EM, Xiao W, Tickle T, Rider J, Gevers D, Franzosa EA, Davey ME, Gillison ML, Huttenhower C (2017) Alterations in oral bacterial communities are associated with risk factors for oral and oropharyngeal cancer. Sci Rep 7(1):17686. https://doi.org/10.1038/s41598-017-17795-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burleigh MC, Liddle L, Monaghan C, Muggeridge DJ, Sculthorpe N, Butcher JP, Henriquez FL, Allen JD, Easton C (2018) Salivary nitrite production is elevated in individuals with a higher abundance of oral nitrate-reducing bacteria. Free Radic Biol Med 120:80–88

    CAS  PubMed  Google Scholar 

  • Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336. https://doi.org/10.1038/nmeth.f.303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cekici A, Kantarci A, Hasturk H, Van Dyke TE (2014) Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontology 64(1):57–80

    Google Scholar 

  • Choudhary MM, France TJ, Teknos TN, Kumar P (2016) Interleukin-6 role in head and neck squamous cell carcinoma progression. World J Otorhinolaryngol Head Neck Surg 2(2):90–97

    PubMed  PubMed Central  Google Scholar 

  • Chowdhry R, Singh N, Sahu DK, Tripathi RK, Mishra A, Singh A, Mukerjee I, Lal N, Bhatt MLB, Kant R (2019) Dysbiosis and variation in predicted functions of the granulation tissue microbiome in HPV positive and negative severe chronic periodontitis. Biomed Res Int 2019:8163591

    PubMed  PubMed Central  Google Scholar 

  • Cui X, Liu J, Xiao W, Chu Y, Ouyang X (2019) Subgingival microbiome in Chinese patients with generalized aggressive periodontitis compared to healthy controls. Arch Oral Biol 101:92–99. https://doi.org/10.1016/j.archoralbio.2019.02.012

    Article  CAS  PubMed  Google Scholar 

  • Decsi G, Soki J, Pap B, Dobra G, Harmati M, Kormondi S, Pankotai T, Braunitzer G, Minarovits J, Sonkodi I, Urban E, Nemeth IB, Nagy K, Buzas K (2019) Chicken or the egg: microbial alterations in biopsy samples of patients with oral potentially malignant disorders. Pathol Oncol Res 25(3):1023–1033. https://doi.org/10.1007/s12253-018-0457-x

    Article  CAS  PubMed  Google Scholar 

  • DeSantis TZ, Hugenholtz P, Larsen N, et al (2006) Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 72(7):5069–5072

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG (2010) The human oral microbiome. J Bacteriol 192(19):5002–5017. https://doi.org/10.1128/JB.00542-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drago L, Vassena C, Saibene AM, Del Fabbro M, Felisati G (2013) A case of coinfection in a chronic maxillary sinusitis of odontogenic origin: identification of Dialister pneumosintes. J Endod 39:1084–1087

    PubMed  Google Scholar 

  • Du Q, Fu M, Zhou Y, Cao Y, Guo T, Zhou Z, Li M, Peng X, Zheng X, Li Y, Xu X, He J, Zhou X (2020) Sucrose promotes caries progression by disrupting the microecological balance in oral biofilms: an in vitro study. Sci Rep 10(1):2961

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eberhard J, Jepsen S, Pohl L, Albers HK, Açil Y (2002) Bacterial challenge stimulates formation of arachidonic acid metabolites by human keratinocytes and neutrophils in vitro. Clin Diagn Lab Immunol 9(1):132–137

    CAS  PubMed  PubMed Central  Google Scholar 

  • Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26(19):2460–2461. https://doi.org/10.1093/bioinformatics/btq461

    Article  CAS  PubMed  Google Scholar 

  • Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D, Forman D, Bray F (2013) Globocan 2012 v1.0, cancer incidence and mortality worldwide: IARC cancerbase no. 11. Lyon (France): International Agency for Research on Cancer. http://globocan.iarc.fr. Accessed 8 Mar 2018

  • Furuya R, Onoye Y, Kanayama A, Saika T, Iyoda T, Tatewaki M, Matsuzaki K, Kobayashi I, Tanaka M (2007) Antimicrobial resistance in clinical isolates of Neisseria subflava from the oral cavities of a Japanese population. J Infect Chemother 13(5):302–304

    CAS  PubMed  Google Scholar 

  • Garavaglia M, Rossi E, Landini P (2012) The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm determinants in Escherichia coli. PLoS One 7(2):e31252

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gaujoux R, Seoighe C (2010) A flexible R package for nonnegative matrix factorization. BMC Bioinform 11:367. https://doi.org/10.1186/1471-2105-11-367

    Article  CAS  Google Scholar 

  • Gholizadeh P, Eslami H, Yousefi M, Asgharzadeh M, Aghazadeh M, Kafil HS (2016) Role of oral microbiome on oral cancers, a review. Biomed Pharmacother 84:552–558. https://doi.org/10.1016/j.biopha.2016.09.082

    Article  CAS  PubMed  Google Scholar 

  • Guerrero-Preston R, Godoy-Vitorino F, Jedlicka A, Rodríguez-Hilario A, González H, Bondy J, Lawson F, Folawiyo O, Michailidi C, Dziedzic A, Thangavel R, Hadar T, Noordhuis MG, Westra W, Koch W, Sidransky D (2016) 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment. Oncotarget 7(32):51320–51334

    PubMed  PubMed Central  Google Scholar 

  • Ha NH, Woo BH, Kim DJ, Ha ES, Choi JI, Kim SJ, Park BS, Lee JH, Park HR (2015) Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties. Tumour Biol 36(12):9947–9960

    CAS  PubMed  Google Scholar 

  • Hashimoto K, Shimizu D, Hirabayashi S, Ueda S, Miyabe S, Oh-Iwa I, Nagao T, Shimozato K, Nomoto S (2019) Changes in oral microbial profiles associated with oral squamous cell carcinoma vs leukoplakia. J Investig Clin Dent 10:e12445

    PubMed  Google Scholar 

  • Hayes RB, Ahn J, Fan X, Peters BA, Ma Y, Yang L, Agalliu I, Burk RD, Ganly I, Purdue MP, Freedman ND, Gapstur SM, Pei Z (2018) Association of oral microbiome with risk for incident head and neck squamous cell cancer. JAMA Oncol 4(3):358–365. https://doi.org/10.1001/jamaoncol.2017.4777

    Article  PubMed  PubMed Central  Google Scholar 

  • Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J (2019) Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci USA 116(26):12672–12677

    CAS  PubMed  Google Scholar 

  • Hernandez BY, Zhu X, Goodman MT, Gatewood R, Mendiola P, Quinata K, Paulino YC (2017) Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS One 12(2):e0172196

    PubMed  PubMed Central  Google Scholar 

  • Hooper SJ, Crean SJ, Lewis MA, Spratt DA, Wade WG, Wilson MJ (2006) Viable bacteria present within oral squamous cell carcinoma tissue. J Clin Microbiol 44(5):1719–1725

    PubMed  PubMed Central  Google Scholar 

  • Horvath A, Rainer F, Bashir M, Leber B, Schmerboeck B, Klymiuk I, Groselj-Strele A, Durdevic M, Freedberg DE, Abrams JA, Fickert P, Stiegler P, Stadlbauer V (2019) Biomarkers for oralization during long-term proton pump inhibitor therapy predict survival in cirrhosis. Sci Rep 9(1):12000

    PubMed  PubMed Central  Google Scholar 

  • Hu X, Zhang Q, Hua H, Chen F (2016) Changes in the salivary microbiota of oral leukoplakia and oral cancer. Oral Oncol 56:e6–e8

    PubMed  Google Scholar 

  • Hu YL, Pang W, Huang Y, Zhang Y, Zhang CJ (2018) The gastric microbiome is perturbed in advanced gastric adenocarcinoma identified through shotgun metagenomics. Front Cell Infect Microbiol 8:433

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huson DH, Auch AF, Qi J, Schuster SC (2007) MEGAN analysis of metagenomic data. Genome Res 17(3):377–386

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jensen A, Fagö-Olsen H, Sørensen CH, Kilian M (2013) Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One 8(2):e56418

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jie Bao G, Kari K, Tervahartiala T, Sorsa T, Meurman JH (2008) Proteolytic activities of oral bacteria on ProMMP-9 and the effect of synthetic proteinase inhibitors. Open Dent J. 2:96–102

    PubMed  PubMed Central  Google Scholar 

  • Kaakoush NO, Castaño-Rodríguez N, Mitchell HM, Man SM (2015) Global epidemiology of Campylobacter infection. Clin Microbiol Rev 28(3):687–720

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kajikawa A, Midorikawa E, Masuda K et al (2016) Characterization of flagellins isolated from a highly motile strain of Lactobacillus agilis. BMC Microbiol 16:49

    PubMed  PubMed Central  Google Scholar 

  • Kirst ME, Li EC, Alfant B, Chi YY, Walker C, Magnusson I, Wang GP (2015) Dysbiosis and alterations in predicted functions of the subgingival microbiome in chronic periodontitis. Appl Environ Microbiol 81(2):783–793. https://doi.org/10.1128/AEM.02712-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi T, Uchibori S, Tsuzukibashi O, Goto H, Aida M (2012) A selective medium for Rothia mucilaginosa and its distribution in oral cavities. J Microbiol Methods 91:364–365

    PubMed  Google Scholar 

  • Kondo Y, Sato K, Nagano K, Nishiguchi M, Hoshino T, Fujiwara T, Nakayama K (2018) Involvement of PorK, a component of the type IX secretion system, Prevotella melaninogenica pathogenicity. Microbiol Immunol 62(9):554–566

    CAS  PubMed  Google Scholar 

  • Lam SY, Yu J, Wong SH, Peppelenbosch MP, Fuhler GM (2017) The gastrointestinal microbiota and its role in oncogenesis. Best Pract Res Clin Gastroenterol 31(6):607–618

    CAS  PubMed  Google Scholar 

  • Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C (2013) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31(9):814–821. https://doi.org/10.1038/nbt.2676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen JM (2017) The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology 151(4):363–374

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lax AJ, Thomas W (2002) How bacteria could cause cancer: one step at a time. Trends Microbiol 10:293–299

    CAS  PubMed  Google Scholar 

  • Le B, Yang SH (2018) Efficacy of Lactobacillus plantarum in prevention of inflammatory bowel disease. Toxicol Rep 5:314–317

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee WH, Chen HM, Yang SF, Liang C, Peng CY, Lin FM, Tsai LL, Wu BC, Hsin CH, Chuang CY, Yang T, Yang TL, Ho SY, Chen WL, Ueng KC, Huang HD, Huang CN, Jong YJ (2017) Bacterial alterations in salivary microbiota and their association in oral cancer. Sci Rep 7(1):16540. https://doi.org/10.1038/s41598-017-16418-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee LT, Wong YK, Hsiao HY, Wang YW, Chan MY, Chang KW (2018) Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg 47(6):699–707

    CAS  PubMed  Google Scholar 

  • Lim Y, Fukuma N, Totsika M, Kenny L, Morrison M, Punyadeera C (2018) The performance of an oral microbiome biomarker panel in predicting oral cavity and oropharyngeal cancers. Front Cell Infect Microbiol 8:267

    PubMed  PubMed Central  Google Scholar 

  • Lisa Cheng YS, Jordan L, Gorugantula LM, Schneiderman E, Chen HS, Rees T (2014) Salivary interleukin-6 and -8 in patients with oral cancer and patients with chronic oral inflammatory diseases. J Periodontol 85:956–965

    PubMed  Google Scholar 

  • Liu S, Chen M, Wang Y, Zhou X, Peng X, Ren B, Li M, Cheng L (2020) Effect of Veillonella parvula on the physiological activity of Streptococcus mutans. Arch Oral Biol 109:104578

    CAS  PubMed  Google Scholar 

  • Long X, Wong CC, Tong L, Chu ESH, Ho Szeto C, Go MYY, Coker OO, Chan AWH, Chan FKL, Sung JJY, Yu J (2019) Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity. Nat Microbiol 4(12):2319–2330

    PubMed  Google Scholar 

  • Ma N, Yang D, Okamura H, Teramachi J, Hasegawa T, Qiu L, Haneji T (2017) Involvement of interleukin-23 induced by Porphyromonas endodontalis lipopolysaccharide in osteoclastogenesis. Mol Med Rep 15(2):559–566

    CAS  PubMed  Google Scholar 

  • Mashima I, Theodorea CF, Thaweboon B, Thaweboon S, Scannapieco FA, Nakazawa F (2017) Exploring the salivary microbiome of children stratified by the oral hygiene index. PLoS One 12(9):e0185274

    PubMed  PubMed Central  Google Scholar 

  • Matera G, Muto V, Vinci M, Zicca E, Abdollahi-Roodsaz S, van de Veerdonk FL, Kullberg BJ, Liberto MC, van der Meer JW, Focà A, Netea MG, Joosten LA (2009) Receptor recognition of and immune intracellular pathways for Veillonella parvula lipopolysaccharide. Clin Vaccine Immunol 16(12):1804–1809

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mirucki CS, Abedi M, Jiang J, Zhu Q, Wang YH, Safavi KE, Clark RB, Nichols FC (2014) Biologic activity of Porphyromonas endodontalis complex lipids. J Endod 40(9):1342–1348

    PubMed  PubMed Central  Google Scholar 

  • Moffatt CE, Whitmore SE, Griffen AL, Leys EJ, Lamont RJ (2011) Filifactor alocis interactions with gingival epithelial cells. Mol Oral Microbiol 26(6):365–373

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nishimata H, Ohara-Nemoto Y, Baba TT, Hoshino T, Fujiwara T, Shimoyama Y, Kimura S, Nemoto TK (2014) Identification of dipeptidyl-peptidase (DPP) 5 and DPP7 in Porphyromonas endodontalis, distinct from those in Porphyromonas gingivalis. PLoS One 9(12):e114221

    PubMed  PubMed Central  Google Scholar 

  • Ohara-Nemoto Y, Shimoyama Y, Nakasato M et al (2018) Distribution of dipeptidyl peptidase (DPP) 4, DPP5, DPP7 and DPP11 in human oral microbiota-potent biomarkers indicating presence of periodontopathic bacteria. FEMS Microbiol Lett 365(22):10

    Google Scholar 

  • Panda M, Rai AK, Rahman T, Das A, Das R, Sarma A, Kataki AC, Chattopadhyay I (2019) Alterations of salivary microbial community associated with oropharyngeal and hypopharyngeal squamous cell carcinoma patients. Arch Microbiol. https://doi.org/10.1007/s00203-019-01790-1

    Article  PubMed  Google Scholar 

  • Perera M, Al-Hebshi NN, Perera I, Ipe D, Ulett GC, Speicher DJ, Chen T, Johnson NW (2018) Inflammatory bacteriome and oral squamous cell carcinoma. J Dent Res 97(6):725–732. https://doi.org/10.1177/0022034518767118

    Article  CAS  PubMed  Google Scholar 

  • Prasad G, McCullough M (2013) Chemokines and cytokines as salivary biomarkers for the early diagnosis of oral cancer. Int J Dent 2013:813756

    PubMed  PubMed Central  Google Scholar 

  • Punyani SR, Sathawane RS (2013) Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma. Clin Oral Investig 17(2):517–524

    PubMed  Google Scholar 

  • Pushalkar S, Mane SP, Ji X, Li Y, Evans C, Crasta OR, Morse D, Meagher R, Singh A, Saxena D (2011) Microbial diversity in saliva of oral squamous cell carcinoma. FEMS Immunol Med Microbiol 61(3):269–277

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pushalkar S, Ji X, Li Y, Estilo C, Yegnanarayana R, Singh B, Li X, Saxena D (2012) Comparison of oral microbiota in tumor and non-tumor tissues of patients with oral squamous cell carcinoma. BMC Microbiol 12:144

    PubMed  PubMed Central  Google Scholar 

  • Qu L, Yu Y, Qiu L, Yang D, Yan L, Guo J, Jahan R (2017) Sirtuin 1 regulates matrix metalloproteinase-13 expression induced by Porphyromonas endodontalis lipopolysaccharide via targeting nuclear factor-κB in osteoblasts. J Oral Microbiol 9(1):1317578

    PubMed  PubMed Central  Google Scholar 

  • Rainey K, Michalek SM, Wen ZT, Wu H (2019) Glycosyltransferase-mediated biofilm matrix dynamics and virulence of Streptococcus mutans. Appl Environ Microbiol 85(5):e02247-18

    PubMed  PubMed Central  Google Scholar 

  • Sasaki M, Yamaura C, Ohara-Nemoto Y, Tajika S, Kodama Y, Ohya T, Harada R, Kimura S (2005) Streptococcus anginosus infection in oral cancer and its infection route. Oral Dis 11(3):151–156

    CAS  PubMed  Google Scholar 

  • Sasaki M, Kodama Y, Shimoyama Y, Ishikawa T, Kimura S (2018) Aciduricity and acid tolerance mechanisms of Streptococcus anginosus. J Gen Appl Microbiol 27(64):174–175

    Google Scholar 

  • Schmidt BL, Kuczynski J, Bhattacharya A, Huey B, Corby PM, Queiroz EL, Nightingale K, Kerr AR, DeLacure MD, Veeramachaneni R, Olshen AB, Albertson DG (2014) Changes in abundance of oral microbiota associated with oral cancer. PLoS One 9(6):e98741. https://doi.org/10.1371/journal.pone.0098741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulz S, Porsch M, Grosse I, Hoffmann K, Schaller HG, Reichert S (2019) Comparison of the oral microbiome of patients with generalized aggressive periodontitis and periodontitis-free subjects. Arch Oral Biol 99:169–176

    CAS  PubMed  Google Scholar 

  • Secretan B, Straif K, Baan R, Grosse Y, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V, WHO International Agency for Research on Cancer Monograph Working Group (2009) A review of human carcinogens—part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 10(11):1033–1034

    PubMed  Google Scholar 

  • Sharma M, Bairy I, Pai K, Satyamoorthy K, Prasad S, Berkovitz B, Radhakrishnan R (2011) Salivary IL-6 levels in oral leukoplakia with dysplasia and its clinical relevance to tobacco habits and periodontitis. Clin Oral Investig 15(5):705–714

    PubMed  Google Scholar 

  • Shiga K, Tateda M, Saijo S, Hori T, Sato I, Tateno H, Matsuura K, Takasaka T, Miyagi T (2001) Presence of Streptococcus infection in extra-oropharyngeal head and neck squamous cell carcinoma and its implication in carcinogenesis. Oncol Rep 8:245–248

    CAS  PubMed  Google Scholar 

  • Shin JM, Luo T, Kamarajan P, Fenno JC, Rickard AH, Kapila YL (2017) Microbial communities associated with primary and metastatic head and neck squamous cell carcinoma—a high fusobacterial and low streptococcal signature. Sci Rep 7(1):9934

    PubMed  PubMed Central  Google Scholar 

  • Signat B, Roques C, Poulet P, Duffaut D (2011) Fusobacterium nucleatum in periodontal health and disease. Curr Issues Mol Biol 13:25–36

    CAS  PubMed  Google Scholar 

  • Takahashi N (2015) Oral microbiome metabolism: from “who are they?” to “what are they doing?”. J Dent Res 94(12):1628–1637

    CAS  PubMed  Google Scholar 

  • Tampa M, Mitran MI, Mitran CI, Sarbu MI, Matei C, Nicolae I, Caruntu A, Tocut SM, Popa MI, Caruntu C, Georgescu SR (2018) Mediators of inflammation—a potential source of biomarkers in oral squamous cell carcinoma. J Immunol Res 2018:1061780

    PubMed  PubMed Central  Google Scholar 

  • Tan H, Yu Z, Wang C et al (2018) Pilot safety evaluation of a novel strain of Bacteroides ovatus. Front Genet. 9:539

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tateda M, Shiga K, Saijo S, Sone M, Hori T, Yokoyama J, Matsuura K, Takasaka T, Miyagi T (2000) Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis. Int J Mol Med 6(6):699–703

    CAS  PubMed  Google Scholar 

  • Tian L, Wu AK, Friedman J, Waldor MK, Weiss ST, Liu YY (2017) Deciphering functional redundancy in the human microbiome. bioRxiv. https://doi.org/10.1101/176313. https://www.biorxiv.org/content/early/2017/08/14/176313. Accessed 3 June 2018

  • Tsoi H, Chu ESH, Zhang X, Sheng J, Nakatsu G, Ng SC, Chan AWH, Chan FKL, Sung JJY, Yu J (2017) Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology 152(6):1419–1433

    PubMed  Google Scholar 

  • Unus S, Ramabadran S, Lakshmi P, Narasimham Gunasekaran N, Krishnan R (2014) Role of cytokines in oral malignancies. SRM J Res Dent Sci 5:274–279

    Google Scholar 

  • Vanja VB (2015) The significance of salivary cytokines in oral leukoplakia. J Autacoids Horm 5:e128

    Google Scholar 

  • Vesty A, Gear K, Biswas K, Radcliff FJ, Taylor MW, Douglas RG (2018) Microbial and inflammatory-based salivary biomarkers of head and neck squamous cell carcinoma. Clin Exp Dent Res 4(6):255–262

    PubMed  PubMed Central  Google Scholar 

  • Vogelmann R, Amieva MR (2007) The role of bacterial pathogens in cancer. Curr Opin Microbiol 10:76–81

    CAS  PubMed  Google Scholar 

  • Wang Q, Wright CJ, Dingming H, Uriarte SM, Lamont RJ (2013) Oral community interactions of Filifactor alocis in vitro. PLoS One 8(10):e76271

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Funchain P, Bebek G, Altemus J, Zhang H, Niazi F, Peterson C, Lee WT, Burkey BB, Eng C (2017) Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas. Genome Med 9:14

    PubMed  PubMed Central  Google Scholar 

  • Wolf A, Moissl-Eichinger C, Perras A, Koskinen K, Tomazic PV, Thurnher D (2017) The salivary microbiome as an indicator of carcinogenesis in patients with oropharyngeal squamous cell carcinoma: a pilot study. Sci Rep 7:5867

    PubMed  PubMed Central  Google Scholar 

  • Wu J, Peters BA, Dominianni C, Zhang Y, Pei Z, Yang L, Ma Y, Purdue MP, Jacobs EJ, Gapstur SM, Li H, Alekseyenko AV, Hayes RB, Ahn J (2016) Cigarette smoking and the oral microbiome in a large study of American adults. ISME J 10(10):2435–2446

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao J, Grier A, Faustoferri RC, Alzoubi S, Gill AL, Feng C, Liu Y, Quivey RG, Kopycka-Kedzierawski DT, Koo H, Gill SR (2018) Association between oral candida and bacteriome in children with severe ECC. J Dent Res 97(13):1468–1476

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yadav DS, Chattopadhyay I, Verma A, Devi TR, Singh LC, Sharma JD, Kataki ACh, Saxena S, Kapur S (2014) A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India. Tumour Biol 35(9):9317–9330

    PubMed  Google Scholar 

  • Yang CY, Yeh YM, Yu HY, Chin CY, Hsu CW, Liu H, Huang PJ, Hu SN, Liao CT, Chang KP, Chang YL (2018) Oral microbiota community dynamics associated with oral squamous cell carcinoma staging. Front Microbiol 9:862

    PubMed  PubMed Central  Google Scholar 

  • Zhang Z, Yang J, Feng Q, Chen B, Li M, Liang C, Li M, Li Z, Xu Q, Zhang L, Chen W (2019) Compositional and functional analysis of the microbiome in tissue and saliva of oral squamous cell carcinoma. Front Microbiol 10:1439

    PubMed  PubMed Central  Google Scholar 

  • Zhao H, Chu M, Huang Z, Yang X, Ran S, Hu B, Zhang C, Liang J (2017) Variations in oral microbiota associated with oral cancer. Sci Rep 7(1):11773

    PubMed  PubMed Central  Google Scholar 

  • Zhou M, Rong R, Munro D, Zhu C, Gao X, Zhang Q, Dong Q (2013) Investigation of the effect of type 2 diabetes mellitus on subgingival plaque microbiota by high-throughput 16S rDNA pyrosequencing. PLoS One 8(4):e61516. https://doi.org/10.1371/journal.pone.0061516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are thankful to Genotypic Technology Pvt Ltd, Bangalore, India for providing metagenomic sequencing services.

Funding

The authors are thankful to NER-BPMC, Department of Biotechnology, New Delhi, India for funding the research grant (Grant no. BT/PR16886/NER/95/336/2015).

Author information

Author notes

  1. Avdhesh Kumar Rai and Madhusmita Panda have equal contribution.

Authors and Affiliations

  1. Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, 610101, India

    Madhusmita Panda & Indranil Chattopadhyay

  2. Dr. B. Borooah Cancer Institute, A. K. Azad Road, Gopinath Nagar, Guwahati, Assam, 16, India

    Avdhesh Kumar Rai, Ashok Kumar Das, Tashnin Rahman, Rajjyoti Das, Kishore Das, Anupam Sarma & Amal Ch. Kataki

Authors
  1. Avdhesh Kumar Rai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madhusmita Panda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashok Kumar Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tashnin Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rajjyoti Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kishore Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anupam Sarma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amal Ch. Kataki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Indranil Chattopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Indranil Chattopadhyay.

Ethics declarations

Conflict of interest

The author declares that there is no competing interest.

Ethics approval and consent to participate

Institutional Human Ethical Committee of Dr. B. Borooah Cancer Institute (BBCI), Guwahati, Assam, India was ethically approved this study (no. BBCI/IEC-26/03).

Additional information

Communicated by Erko Stackebrandt.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 315 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rai, A.K., Panda, M., Das, A.K. et al. Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation. Arch Microbiol 203, 137–152 (2021). https://doi.org/10.1007/s00203-020-02011-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00203-020-02011-w

Keywords

Search

Navigation