牙周致病菌与消化系统肿瘤相关性的研究进展

doi:10.13591/j.cnki.kqyx.2025.09.009

Abstract

Abstract:

Periodontitis is closely associated with various systemic diseases, and emerging studies have reported its promotive effect on gastrointestinal tumors. Periodontal pathogens can ectopically colonize tumor sites in the gastrointestinal system, directly regulate tumor cells, shape a pro-inflammatory microenvironment, and modulate immune responses, thereby promoting tumor initiation and progression. This review summarizes the research progress of periodontal pathogens in promoting gastrointestinal tumors, aiming to elucidate their underlying mechanisms and provide insights for translational research and clinical applications.

Key words: periodontitis, gastrointestinal tumors, periodontal pathogens, tumor progression, tumor microenvironment

CLC Number:

R781.4

LI Haoyu, WU Yikuan, DING Peihui, LI Xiaojun. Research progress of the correlation between periodontal pathogens and gastrointestinal tumors[J]. Stomatology, 2025, 45(9): 691-695.

References 45

[1]	Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020[J]. Chin Med J (Engl), 2021, 134(7): 783-791.
[2]	Arnold M, Abnet CC, Neale RE, et al. Global burden of 5 major types of gastrointestinal cancer[J]. Gastroenterology, 2020, 159(1): 335-349.e15. doi: S0016-5085(20)30452-2 pmid: 32247694
[3]	Peery AF, Crockett SD, Murphy CC, et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: Update 2018[J]. Gastroenterology, 2019, 156(1): 254-272. e11 doi: S0016-5085(18)35147-3 pmid: 30315778
[4]	Nascimento GG, Alves-Costa S, Romandini M. Burden of severe periodontitis and edentulism in 2021, with projections up to 2050: The Global Burden of Disease 2021 study[J]. J Periodontal Res, 2024, 59(5): 823-867.
[5]	Zhang Y, Sun CY, Song EJ, et al. Is periodontitis a risk indicator for gastrointestinal cancers? A meta-analysis of cohort studies[J]. J Clin Periodontol, 2020, 47(2): 134-147. doi: 10.1111/jcpe.13217 pmid: 31697412
[6]	Maisonneuve P, Amar S, Lowenfels AB. Periodontal disease, edentulism, and pancreatic cancer: A meta-analysis[J]. Ann Oncol, 2017, 28(5): 985-995. doi: 10.1093/annonc/mdx019 pmid: 28453689
[7]	Li WQ, Xu JY, Zhang RY, et al. Is periodontal disease a risk indicator for colorectal cancer? A systematic review and meta-analysis[J]. J Clin Periodontol, 2021, 48(3): 336-347. doi: 10.1111/jcpe.13402 pmid: 33179280
[8]	Chen SH, Chen JF, Hung YT, et al. Exploring the relationship between periodontitis, anti-periodontitis therapy, and extra-oral cancer risk: Findings from a nationwide population-based study[J]. Biomedicines, 2023, 11(7): 1949.
[9]	Yoshihara T, Kioi M, Baba J, et al. A prospective interventional trial on the effect of periodontal treatment on Fusobacterium nucleatum abundance in patients with colorectal tumours[J]. Sci Rep, 2021, 11(1): 23719. doi: 10.1038/s41598-021-03083-4 pmid: 34887459
[10]	Flemer B, Warren RD, Barrett MP, et al. The oral microbiota in colorectal cancer is distinctive and predictive[J]. Gut, 2018, 67(8): 1454-1463. doi: 10.1136/gutjnl-2017-314814 pmid: 28988196
[11]	Fan XZ, Alekseyenko AV, Wu J, et al. Human oral microbiome and prospective risk for pancreatic cancer: A population-based nested case-control study[J]. Gut, 2018, 67(1): 120-127. doi: 10.1136/gutjnl-2016-312580 pmid: 27742762
[12]	徐依萍, 黄嘉玲, 刘忠斌, 等. 具核梭杆菌与口腔鳞状细胞癌关系的研究进展[J]. 口腔医学, 2023, 43(6): 546-551.
[13]	Rashidi A, Ebadi M, Weisdorf DJ, et al. No evidence for colonization of oral bacteria in the distal gut in healthy adults[J]. Proc Natl Acad Sci USA, 2021, 118(42): e2114152118.
[14]	Kunath BJ, De Rudder C, Laczny CC, et al. The oral-gut microbiome axis in health and disease[J]. Nat Rev Microbiol, 2024, 22(12): 791-805.
[15]	Zhou YF, Qin Y, Ma JJ, et al. Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment[J]. Exp Hematol Oncol, 2024, 13(1): 33.
[16]	Chen MF, Lu MS, Hsieh CC, et al. Porphyromonas gingivalis promotes tumor progression in esophageal squamous cell carcinoma[J]. Cell Oncol (Dordr), 2021, 44(2): 373-384.
[17]	Liang MX, Liu YW, Zhang ZY, et al. Fusobacterium nucleatum induces MDSCs enrichment via activation the NLRP3 inflammosome in ESCC cells, leading to cisplatin resistance[J]. Ann Med, 2022, 54(1): 989-1003.
[18]	Hernández-Cabanyero C, Vonaesch P. Ectopic colonization by oral bacteria as an emerging theme in health and disease[J]. FEMS Microbiol Rev, 2024, 48(2): fuae012.
[19]	Horliana ACRT, Chambrone L, Foz AM, et al. Dissemination of periodontal pathogens in the bloodstream after periodontal procedures: A systematic review[J]. PLoS One, 2014, 9(5): e98271.
[20]	Xue Y, Xiao H, Guo SH, et al. Indoleamine 2, 3-dioxygenase expression regulates the survival and proliferation of Fusobacterium nucleatum in THP-1-derived macrophages[J]. Cell Death Dis, 2018, 9(3): 355.
[21]	Bostanghadiri N, Razavi S, Shariati A, et al. Exploring the interplay between Fusobacterium nucleatum with the expression of microRNA, and inflammatory mediators in colorectal cancer[J]. Front Microbiol, 2023, 14: 1302719.
[22]	Tan Q, Ma X, Yang B, et al. Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils[J]. Gut Microbes, 2022, 14(1): 2073785.
[23]	Li TJ, Hao YH, Tang YL, et al. Periodontal pathogens: A crucial link between periodontal diseases and oral cancer[J]. Front Microbiol, 2022, 13: 919633.
[24]	Peng RT, Sun Y, Zhou XD, et al. Treponema denticola promotes OSCC development via the TGF-β signaling pathway[J]. J Dent Res, 2022, 101(6): 704-713.
[25]	Chen SM, Hsu LJ, Lee HL, et al. Lactobacillus attenuate the progression of pancreatic cancer promoted by Porphyromonas gingivalis in K-ras^G¹²^D transgenic mice[J]. Cancers (Basel), 2020, 12(12): 3522.
[26]	Udayasuryan B, Ahmad RN, Nguyen TTD, et al. Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling[J]. Sci Signal, 2022, 15(756): eabn4948.
[27]	Ha NH, Park DG, Woo BH, et al. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs[J]. Cytokine, 2016, 86: 64-72. doi: S1043-4666(16)30181-8 pmid: 27468958
[28]	Casasanta MA, Yoo CC, Udayasuryan B, et al. Fusobacterium nucleatum host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration[J]. Sci Signal, 2020, 13(641): eaba9157.
[29]	Hayashi M, Ikenaga N, Nakata K, et al. Intratumor Fusobacterium nucleatum promotes the progression of pancreatic cancer via the CXCL1-CXCR2 axis[J]. Cancer Sci, 2023, 114(9): 3666-3678.
[30]	Yáñez L, Soto C, Tapia H, et al. Co-culture of P. gingivalis and F. nucleatum synergistically elevates IL-6 expression via TLR4 signaling in oral keratinocytes[J]. Int J Mol Sci, 2024, 25(7): 3611.
[31]	Brennan CA, Clay SL, Lavoie SL, et al. Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression[J]. Gut Microbes, 2021, 13(1): 1987780. doi: 10.1080/19490976.2021.1987780 pmid: 34781821
[32]	Ternes D, Tsenkova M, Pozdeev VI, et al. The gut microbial metabolite formate exacerbates colorectal cancer progression[J]. Nat Metab, 2022, 4(4): 458-475. doi: 10.1038/s42255-022-00558-0 pmid: 35437333
[33]	Saito T, Nishikawa H, Wada H, et al. Two FOXP3⁺CD4⁺ T cell subpopulations distinctly control the prognosis of colorectal cancers[J]. Nat Med, 2016, 22(6): 679-684.
[34]	Liu SY, Zhou XD, Peng X, et al. Porphyromonas gingivalis promotes immunoevasion of oral cancer by protecting cancer from macrophage attack[J]. J Immunol, 2020, 205(1): 282-289. doi: 10.4049/jimmunol.1901138 pmid: 32471882
[35]	Xu CC, Fan LN, Lin YF, et al. Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization[J]. Gut Microbes, 2021, 13(1): 1980347.
[36]	Shin AE, Tesfagiorgis Y, Larsen F, et al. F4/80⁺Ly6C^high macrophages lead to cell plasticity and cancer initiation in colitis[J]. Gastroenterology, 2023, 164(4): 593-609.e13.
[37]	Yamane T, Kanamori Y, Sawayama H, et al. Iron accelerates Fusobacterium nucleatum-induced CCL8 expression in macrophages and is associated with colorectal cancer progression[J]. JCI Insight, 2022, 7(21): e156802.
[38]	Wen L, Mu W, Lu H, et al. Porphyromonas gingivalis promotes oral squamous cell carcinoma progression in an immune microenvironment[J]. J Dent Res, 2020, 99(6): 666-675. doi: 10.1177/0022034520909312 pmid: 32298192
[39]	Wang XP, Liu YW, Lu YN, et al. Clinical impact of Fn-induced high expression of KIR2DL1 in CD8 T lymphocytes in oesophageal squamous cell carcinoma[J]. Ann Med, 2022, 54(1): 51-62.
[40]	Sakamoto Y, Mima K, Ishimoto T, et al. Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis[J]. Cancer Sci, 2021, 112(11): 4470-4477.
[41]	Ren JL, Han X, Lohner H, et al. gingivalis infection upregulates PD-L1 expression on dendritic cells, suppresses CD8⁺ T-cell responses, and aggravates oral cancer[J]. Cancer Immunol Res, 2023, 11(3): 290-305.
[42]	Jiang SS, Xie YL, Xiao XY, et al. Fusobacterium nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer[J]. Cell Host Microbe, 2023, 31(5): 781-797.e9.
[43]	Gao YH, Bi DX, Xie RT, et al. Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer[J]. Signal Transduct Target Ther, 2021, 6(1): 398.
[44]	Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack[J]. Immunity, 2015, 42(2): 344-355.
[45]	Kim YJ, Kim BK, Park SJ, et al. Impact of Fusobacterium nucleatum in the gastrointestinal tract on natural killer cells[J]. World J Gastroenterol, 2021, 27(29): 4879-4889.

Research progress of the correlation between periodontal pathogens and gastrointestinal tumors

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