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Review Article

Periodontitis increases the risk of gastrointestinal dysfunction: an update on the plausible pathogenic molecular mechanisms

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Received 04 Nov 2023, Accepted 01 Apr 2024, Published online: 11 Apr 2024

References

  • Adams RA, Bauer J, Flick MJ, Sikorski SL, Nuriel T, Lassmann H, Degen JL, Akassoglou K. 2007. The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J Exp Med. 204(3):571–582. doi: 10.1084/jem.20061931.
  • Adibrad M, Deyhimi P, Ganjalikhani Hakemi M, Behfarnia P, Shahabuei M, Rafiee L. 2012. Signs of the presence of Th17 cells in chronic periodontal disease. J Periodontal Res. 47(4):525–531. doi: 10.1111/j.1600-0765.2011.01464.x.
  • Ahn J, Segers S, Hayes RB. 2012. Periodontal disease, Porphyromonas gingivalis serum antibody levels and orodigestive cancer mortality. Carcinogenesis. 33(5):1055–1058. doi: 10.1093/carcin/bgs112.
  • Ahrenstedt O, Knutson L, Nilsson B, Nilsson-Ekdahl K, Odlind B, Hällgren R. 1990. Enhanced local production of complement components in the small intestines of patients with Crohn’s disease. N Engl J Med. 322(19):1345–1349. doi: 10.1056/NEJM199005103221903.
  • Al Asqah M, Al Hamoudi N, Anil S, Al Jebreen A, Al-Hamoudi WK. 2009. Is the presence of Helicobacter pylori in dental plaque of patients with chronic periodontitis a risk factor for gastric infection? Can J Gastroenterol. 23(3):177–179. doi: 10.1155/2009/950527.
  • Alarcón P, González M, Castro É. 2016. Rol de la microbiota gastrointestinal en la regulación de la respuesta inmune [The role of gut microbiota in the regulation of the immune response]. Rev Med Chil. 144(7):910–916. Spanish. doi: 10.4067/S0034-98872016000700013.
  • Albuquerque-Souza E, Sahingur SE. 2022. Periodontitis, chronic liver diseases, and the emerging oral-gut-liver axis. Periodontol 2000. 89(1):125–141. doi: 10.1111/prd.12427.
  • Aliberti J, Viola JP, Vieira-de-Abreu A, Bozza PT, Sher A, Scharfstein J. 2003. Cutting edge: bradykinin induces IL-12 production by dendritic cells: a danger signal that drives Th1 polarization. J Immunol. 170(11):5349–5353. doi: 10.4049/jimmunol.170.11.5349.
  • Altaf-Ul-Amin M, Karim MB, Hu P, Ono N, Kanaya S. 2020. Discovery of inflammatory bowel disease-associated miRNAs using a novel bipartite clustering approach. BMC Med Genomics. 13(Suppl 3):10. doi: 10.1186/s12920-020-0660-y.
  • Anderson HC, McCARTY M. 1951. The occurrence in the rabbit of an acute phase protein analogous to human C reactive protein. J Exp Med. 93(1):25–36. doi: 10.1084/jem.93.1.25.
  • Andresen L, Jørgensen VL, Perner A, Hansen A, Eugen-Olsen J, Rask-Madsen J. 2005. Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut. 54(4):503–509. doi: 10.1136/gut.2003.034165.
  • Andrukhov O, Ulm C, Reischl H, Nguyen PQ, Matejka M, Rausch-Fan X. 2011. Serum cytokine levels in periodontitis patients in relation to the bacterial load. J Periodontol. 82(6):885–892. doi: 10.1902/jop.2010.100425.
  • Ansari SA, Iqbal MUN, Khan TA, Kazmi SU. 2018. Association of oral Helicobacter pylori with gastric complications. Life Sci. 205:125–130. doi: 10.1016/j.lfs.2018.05.026.
  • Anton PA, Shanahan F. 1998. Neuroimmunomodulation in inflammatory bowel disease. How far from "bench" to "bedside"? Ann N Y Acad Sci. 840(1):723–734. doi: 10.1111/j.1749-6632.1998.tb09611.x.
  • Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K, Koga Y, Sudo N. 2012. Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol. 303(11):G1288–95. doi: 10.1152/ajpgi.00341.2012.
  • Atarashi K, Suda W, Luo C, Kawaguchi T, Motoo I, Narushima S, Kiguchi Y, Yasuma K, Watanabe E, Tanoue T, et al. 2017. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science. 358(6361):359–365. doi: 10.1126/science.aan4526.
  • Aviello G, Knaus UG. 2017. ROS in gastrointestinal inflammation: rescue Or Sabotage? Br J Pharmacol. 174(12):1704–1718. doi: 10.1111/bph.13428.
  • Azer SA. 2013. Overview of molecular pathways in inflammatory bowel disease associated with colorectal cancer development. Eur J Gastroenterol Hepatol. 25(3):271–281. doi: 10.1097/MEG.0b013e32835b5803.
  • Azuma H, Kido J, Ikedo D, Kataoka M, Nagata T. 2004. Substance P enhances the inhibition of osteoblastic cell differentiation induced by lipopolysaccharide from Porphyromonas gingivalis. J Periodontol. 75(7):974–981. doi: 10.1902/jop.2004.75.7.974.
  • Babbs CF. 1992. Oxygen radicals in ulcerative colitis. Free Radic Biol Med. 13(2):169–181. doi: 10.1016/0891-5849(92)90079-v.
  • Baert FJ, D’Haens GR, Peeters M, Hiele MI, Schaible TF, Shealy D, Geboes K, Rutgeerts PJ. 1999. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn’s ileocolitis. Gastroenterology. 116(1):22–28. doi: 10.1016/s0016-5085(99)70224-6.
  • Bainbridge BW, Darveau RP. 2001. Porphyromonas gingivalis lipopolysaccharide: an unusual pattern recognition receptor ligand for the innate host defense system. Acta Odontol Scand. 59(3):131–138. doi: 10.1080/000163501750266710.
  • Bajaj JS, Betrapally NS, Hylemon PB, Heuman DM, Daita K, White MB, Unser A, Thacker LR, Sanyal AJ, Kang DJ, et al. 2015. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology. 62(4):1260–1271. doi: 10.1002/hep.27819.
  • Ballard J, Shiner M. 1974. Evidence of cytotoxicity in ulcerative colitis from immunofluorescent staining of the rectal mucosa. Lancet. 1(7865):1014–1017. doi: 10.1016/s0140-6736(74)90416-4.
  • Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. 2000. Immunobiology of dendritic cells. Annu Rev Immunol. 18(1):767–811. doi: 10.1146/annurev.immunol.18.1.767.
  • Bao K, Reinhardt RL. 2015. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine. 75(1):25–37. doi: 10.1016/j.cyto.2015.05.008.
  • Baruah P, Dumitriu IE, Peri G, Russo V, Mantovani A, Manfredi AA, Rovere-Querini P. 2006. The tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells. J Leukoc Biol. 80(1):87–95. doi: 10.1189/jlb.0805445.
  • Bazzoni F, Rossato M, Fabbri M, Gaudiosi D, Mirolo M, Mori L, Tamassia N, Mantovani A, Cassatella MA, Locati M. 2009. Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc Natl Acad Sci U S A. 106(13):5282–5287. doi: 10.1073/pnas.0810909106.
  • Berkovich L, Gerber M, Katzav A, Kidron D, Avital S. 2022. NF-kappa B expression in resected specimen of colonic cancer is higher compared to its expression in inflammatory bowel diseases and polyps. Sci Rep. 12(1):16645. doi: 10.1038/s41598-022-21078-7.
  • Boirivant M, Amendola A, Butera A, Sanchez M, Xu L, Marinaro M, Kitani A, Di Giacinto C, Strober W, Fuss IJ. 2008. A transient breach in the epithelial barrier leads to regulatory T-cell generation and resistance to experimental colitis. Gastroenterology. 135(5):1612–1623.e5. doi: 10.1053/j.gastro.2008.07.028.
  • Bunte K, Beikler T. 2019. Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases. Int J Mol Sci. 20(14):3394. doi: 10.3390/ijms20143394.
  • Bykov I, Junnikkala S, Pekna M, Lindros KO, Meri S. 2006. Complement C3 contributes to ethanol-induced liver steatosis in mice. Ann Med. 38(4):280–286. doi: 10.1080/07853890600664608.
  • Cao Q, McIsaac SM, Stadnyk AW. 2012. Human colonic epithelial cells detect and respond to C5a via apically expressed C5aR through the ERK pathway. Am J Physiol Cell Physiol. 302(12):C1731–40. doi: 10.1152/ajpcell.00213.2011.
  • Cario E, Gerken G, Podolsky DK. 2004. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology. 127(1):224–238. doi: 10.1053/j.gastro.2004.04.015.
  • Casado-Bed M, Viennois E. 2022. MicroRNA and gut microbiota: tiny but mighty-novel insights into their cross-talk in inflammatory bowel disease pathogenesis and therapeutics. J Crohns Colitis. 16(6):992–1005. doi: 10.1093/ecco-jcc/jjab223.
  • Casarin RCV, Ribeiro EDP, Mariano FS, Nociti FH, Casati MZ, Gonçalves RB. 2010. Levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, inflammatory cytokines and species-specific immunoglobulin G in generalized aggressive and chronic periodontitis. J Periodontal Res. 45(5):635–642. doi: 10.1111/j.1600-0765.2010.01278.x.
  • Castaño-Rodríguez N, Goh KL, Fock KM, Mitchell HM, Kaakoush NO. 2017. Dysbiosis of the microbiome in gastric carcinogenesis. Sci Rep. 7(1):15957. doi: 10.1038/s41598-017-16289-2.
  • Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, et al. 2012. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22(2):299–306. doi: 10.1101/gr.126516.111.
  • Chen Z, Cai J, Chen YM, Wei J, Li HB, Lu Y, Zhou Z, Chen XL. 2019. A meta-analysis of the association between the presence of Helicobacter pylori and periodontal diseases. Medicine (Baltimore). 98(22):e15922. doi: 10.1097/MD.0000000000015922.
  • Chiu AV, Saigh MA, McCulloch CA, Glogauer M. 2017. The role of NrF2 in the regulation of periodontal health and disease. J Dent Res. 96(9):975–983. doi: 10.1177/0022034517715007.
  • Chu L, Dong Z, Xu X, Cochran DL, Ebersole JL. 2002. Role of glutathione metabolism of Treponema denticola in bacterial growth and virulence expression. Infect Immun. 70(3):1113–1120. doi: 10.1128/IAI.70.3.1113-1120.2002.
  • Chu XJ, Cao NW, Zhou HY, Meng X, Guo B, Zhang HY, Li BZ. 2021. The oral and gut microbiome in rheumatoid arthritis patients: a systematic review. Rheumatology (Oxford). 60(3):1054–1066. doi: 10.1093/rheumatology/keaa835.
  • Chung M, Zhao N, Meier R, Koestler DC, Wu G, de Castillo E, Paster BJ, Charpentier K, Izard J, Kelsey KT, et al. 2021. Comparisons of oral, intestinal, and pancreatic bacterial microbiomes in patients with pancreatic cancer and other gastrointestinal diseases. J Oral Microbiol. 13(1):1887680. doi: 10.1080/20002297.2021.1887680.
  • Crome SQ, Wang AY, Kang CY, Levings MK. 2009. The role of retinoic acid-related orphan receptor variant 2 and IL-17 in the development and function of human CD4+ T cells. Eur J Immunol. 39(6):1480–1493. doi: 10.1002/eji.200838908.
  • Cryan JF, Dinan TG. 2012. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 13(10):701–712. doi: 10.1038/nrn3346.
  • Dalal SR, Kwon JH. 2010. The role of MicroRNA in inflammatory bowel disease. Gastroenterol Hepatol (N Y). 6(11):714–722.
  • de Zoete MR, Palm NW, Zhu S, Flavell RA. 2014. Inflammasomes. Cold Spring Harb Perspect Biol. 6(12):a016287–a016287. doi: 10.1101/cshperspect.a016287.
  • Deban L, Russo RC, Sironi M, Moalli F, Scanziani M, Zambelli V, Cuccovillo I, Bastone A, Gobbi M, Valentino S, et al. 2010. Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol. 11(4):328–334. doi: 10.1038/ni.1854.
  • Dejea CM, Sears CL. 2016. Do biofilms confer a pro-carcinogenic state? Gut Microbes. 7(1):54–57. Erratum in: doi: 10.1073/pnas.1406199111. Erratum in: doi: 10.1016/j.cmet.2015.04.011. doi: 10.1080/19490976.2015.1121363.
  • Deplancke B, Gaskins HR. 2003. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. Faseb J. 17(10):1310–1312. doi: 10.1096/fj.02-0883fje.
  • Desta T, Graves DT. 2007. Fibroblast apoptosis induced by Porphyromonas gingivalis is stimulated by a gingipain and caspase-independent pathway that involves apoptosis-inducing factor. Cell Microbiol. 9(11):2667–2675. doi: 10.1111/j.1462-5822.2007.00987.x.
  • Dowman JK, Tomlinson JW, Newsome PN. 2010. Pathogenesis of non-alcoholic fatty liver disease. QJM. 103(2):71–83. doi: 10.1093/qjmed/hcp158.
  • Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, Roslani AC, Wick EC, Mongodin EF, Loke MF, et al. 2017. High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia. NPJ Biofilms Microbiomes. 3(1):34. Erratum in: NPJ Biofilms Microbiomes. 2019 9;5(1):2. doi: 10.1038/s41522-017-0040-3.
  • Elvington M, Schepp-Berglind J, Tomlinson S. 2015. Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis. Clin Exp Immunol. 179(3):500–508. doi: 10.1111/cei.12464.
  • Fagan EA, Dyck RF, Maton PN, Hodgson HJ, Chadwick VS, Petrie A, Pepys MB. 1982. Serum levels of C-reactive protein in Crohn’s disease and ulcerative colitis. Eur J Clin Invest. 12(4):351–359. doi: 10.1111/j.1365-2362.1982.tb02244.x.
  • Fais S, Capobianchi MR, Pallone F, Di Marco P, Boirivant M, Dianzani F, Torsoli A. 1991. Spontaneous release of interferon gamma by intestinal lamina propria lymphocytes in Crohn’s disease. Kinetics of in vitro response to interferon gamma inducers. Gut. 32(4):403–407. doi: 10.1136/gut.32.4.403.
  • Fan X, Alekseyenko AV, Wu J, Peters BA, Jacobs EJ, Gapstur SM, Purdue MP, Abnet CC, Stolzenberg-Solomon R, Miller G, et al. 2018. Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut. 67(1):120–127. Jan doi: 10.1136/gutjnl-2016-312580.
  • Feng T, Qin H, Wang L, Benveniste EN, Elson CO, Cong Y. 2011. Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol. 186(11):6313–6318. doi: 10.4049/jimmunol.1001454.
  • Feng Y, Chen Z, Tu SQ, Wei JM, Hou YL, Kuang ZL, Kang XN, Ai H. 2022. Role of Interleukin-17A in the Pathomechanisms of Periodontitis and Related Systemic Chronic Inflammatory Diseases. Front Immunol. 13:862415. doi: 10.3389/fimmu.2022.862415.
  • Fetissov SO, Hamze Sinno M, Coquerel Q, Do Rego JC, Coëffier M, Gilbert D, Hökfelt T, Déchelotte P. 2008. Emerging role of autoantibodies against appetite-regulating neuropeptides in eating disorders. Nutrition. 24(9):854–859. doi: 10.1016/j.nut.2008.06.021.
  • Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD, Thornton S, Degen JL. 2007. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest. 117(11):3224–3235. doi: 10.1172/JCI30134.
  • Flood B, Oficjalska K, Laukens D, Fay J, O’Grady A, Caiazza F, Heetun Z, Mills KH, Sheahan K, Ryan EJ, et al. 2015. Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer: diagnostic and therapeutic potential. Clin Exp Immunol. 181(1):39–50. doi: 10.1111/cei.12617.
  • Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. 2009. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 10(3):241–247. doi: 10.1038/ni.1703.
  • Franchimont D, Vermeire S, El Housni H, Pierik M, Van Steen K, Gustot T, Quertinmont E, Abramowicz M, Van Gossum A, Devière J, et al. 2004. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn’s disease and ulcerative colitis. Gut. 53(7):987–992. doi: 10.1136/gut.2003.030205.
  • Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y. 2003. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 52(1):65–70. doi: 10.1136/gut.52.1.65.
  • Fukata M, Chen A, Klepper A, Krishnareddy S, Vamadevan AS, Thomas LS, Xu R, Inoue H, Arditi M, Dannenberg AJ, et al. 2006. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: Role in proliferation and apoptosis in the intestine. Gastroenterology. 131(3):862–877. doi: 10.1053/j.gastro.2006.06.017.
  • Gao B, Zheng L. 2013. microRNA expression in rat apical periodontitis bone lesion. Bone Res. 1(2):170–185. doi: 10.4248/BR201302006.
  • Gao SG, Yang JQ, Ma ZK, Yuan X, Zhao C, Wang GC, Wei H, Feng XS, Qi YJ. Preoperative serum immunoglobulin G and A antibodies to Porphyromonas gingivalis are potential serum biomarkers for the diagnosis and prognosis of esophageal squamous cell carcinoma. BMC Cancer. 2018 3;18(1):17. doi: 10.1186/s12885-017-3905-1.
  • Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, et al. 2014. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 15(3):382–392. doi: 10.1016/j.chom.2014.02.005.
  • Goldin E, Karmeli F, Selinger Z, Rachmilewitz D. 1989. Colonic substance P levels are increased in ulcerative colitis and decreased in chronic severe constipation. Dig Dis Sci. 34(5):754–757. doi: 10.1007/BF01540348.
  • Gonçalves Fernandes J, Morford LA, Harrison PL, Kompotiati T, Huang H, Aukhil I, Wallet SM, Macchion Shaddox L. 2020. Dysregulation of genes and microRNAs in localized aggressive periodontitis. J Clin Periodontol. 47(11):1317–1325. doi: 10.1111/jcpe.13361.
  • Goode T, O’Connell J, Anton P, Wong H, Reeve J, O’Sullivan GC, Collins JK, Shanahan F. 2000. Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation. Gut. 47(3):387–396. doi: 10.1136/gut.47.3.387.
  • Goto Y, Panea C, Nakato G, Cebula A, Lee C, Diez MG, Laufer TM, Ignatowicz L, Ivanov II. 2014. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity. 40(4):594–607. doi: 10.1016/j.immuni.2014.03.005.
  • Grąt M, Wronka KM, Krasnodębski M, Masior Ł, Lewandowski Z, Kosińska I, Grąt K, Stypułkowski J, Rejowski S, Wasilewicz M, et al. 2016. Profile of gut microbiota associated with the presence of hepatocellular cancer in patients with liver cirrhosis. Transplant Proc. 48(5):1687–1691. doi: 10.1016/j.transproceed.2016.01.077.
  • Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, et al. 2012. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 491(7423):254–258. doi: 10.1038/nature11465.
  • Groeger S, Jarzina F, Domann E, Meyle J. 2017. Porphyromonas gingivalis activates NFκB and MAPK pathways in human oral epithelial cells. BMC Immunol. 18(1):1. doi: 10.1186/s12865-016-0185-5.
  • Gümüş P, Nizam N, Nalbantsoy A, Özçaka Ö, Buduneli N. 2014. Saliva and serum levels of pentraxin-3 and interleukin-1β in generalized aggressive or chronic periodontitis. J Periodontol. 85(3):e40-6–e46. doi: 10.1902/jop.2013.130281.
  • Guo RF, Riedemann NC, Ward PA. 2004. Role of C5a–C5aR interaction in sepsis. Shock. 21(1):1–7. doi: 10.1097/01.shk.0000105502.75189.5e.
  • Guo W, Ye P, Yu H, Liu Z, Yang P, Hunter N. 2014. CD24 activates the NLRP3 inflammasome through c-Src kinase activity in a model of the lining epithelium of inflamed periodontal tissues. Immun Inflamm Dis. 2(4):239–253. doi: 10.1002/iid3.40.
  • Györfi A, Fazekas A, Rosivall L. 1992. Neurogenic inflammation and the oral mucosa. J Clin Periodontol. 19(10):731–736. doi: 10.1111/j.1600-051x.1992.tb02162.x.
  • Hajishengallis G, Chavakis T. 2021. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 21(7):426–440. doi: 10.1038/s41577-020-00488-6.
  • Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, et al. 2011. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 10(5):497–506. doi: 10.1016/j.chom.2011.10.006.
  • Halstensen TS, Mollnes TE, Fausa O, Brandtzaeg P. 1989. Deposits of terminal complement complex (TCC) in muscularis mucosae and submucosal vessels in ulcerative colitis and Crohn’s disease of the colon. Gut. 30(3):361–366. doi: 10.1136/gut.30.3.361.
  • Halstensen TS, Mollnes TE, Garred P, Fausa O, Brandtzaeg P. 1992. Surface epithelium related activation of complement differs in Crohn’s disease and ulcerative colitis. Gut. 33(7):902–908. Erratum in: Gut 1992 Oct;33(10):1440. doi: 10.1136/gut.33.7.902.
  • Hanna DN, Smith PM, Novitskiy SV, Washington MK, Zi J, Weaver CJ, Hamaamen JA, Lewis KB, Zhu J, Yang J, et al. 2022. SMAD4 suppresses colitis-associated carcinoma through inhibition of CCL20/CCR6-mediated inflammation. Gastroenterology. 163(5):1334–1350.e14. e14. doi: 10.1053/j.gastro.2022.07.016.
  • Harbour SN, Maynard CL, Zindl CL, Schoeb TR, Weaver CT. 2015. Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis. Proc Natl Acad Sci U S A. 112(22):7061–7066. doi: 10.1073/pnas.1415675112.
  • Hausmann M, Kiessling S, Mestermann S, Webb G, Spöttl T, Andus T, Schölmerich J, Herfarth H, Ray K, Falk W, et al. 2002. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology. 122(7):1987–2000. doi: 10.1053/gast.2002.33662.
  • Hernandez BY, Zhu X, Risch HA, Lu L, Ma X, Irwin ML, Lim JK, Taddei TH, Pawlish KS, Stroup AM, et al. 2022. Oral Cyanobacteria and Hepatocellular Carcinoma. Cancer Epidemiol Biomarkers Prev. 31(1):221–229. doi: 10.1158/1055-9965.EPI-21-0804.
  • Hietaranta A, Mustonen H, Puolakkainen P, Haapiainen R, Kemppainen E. 2004. Proinflammatory effects of pancreatic elastase are mediated through TLR4 and NF-kappaB. Biochem Biophys Res Commun. 323(1):192–196. doi: 10.1016/j.bbrc.2004.08.077.
  • Hirsova P, Bamidele AO, Wang H, Povero D, Revelo XS. 2021. Emerging roles of T cells in the pathogenesis of nonalcoholic steatohepatitis and hepatocellular carcinoma. Front Endocrinol (Lausanne). 12:760860. doi: 10.3389/fendo.2021.760860.
  • Holzer P. 1998. Jul-Aug Implications of tachykinins and calcitonin gene-related peptide in inflammatory bowel disease. Digestion. 59(4):269–283. doi: 10.1159/000007504.
  • Hooper LV, Gordon JI. 2001. Commensal host-bacterial relationships in the gut. Science. 292(5519):1115–1118. doi: 10.1126/science.1058709.
  • Hu S, Liu L, Chang EB, Wang JY, Raufman JP. 2015. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Mol Cancer. 14(1):180. doi: 10.1186/s12943-015-0450-x.
  • Hug H, Mohajeri MH, La Fata G. 2018. Toll-Like Receptors: Regulators of the Immune Response in the Human Gut. Nutrients. 10(2):203. doi: 10.3390/nu10020203.
  • Huh JW, Roh TY. 2020. Opportunistic detection of Fusobacterium nucleatum as a marker for the early gut microbial dysbiosis. BMC Microbiol. 20(1):208. doi: 10.1186/s12866-020-01887-4.
  • Hung SC, Huang PR, Almeida-da-Silva CLC, Atanasova KR, Yilmaz O, Ojcius DM. 2018. Oct-Nov NLRX1 modulates differentially NLRP3 inflammasome activation and NF-κB signaling during Fusobacterium nucleatum infection. Microbes Infect. 20(9-10):615–625. doi: 10.1016/j.micinf.2017.09.014.
  • Iborra M, Bernuzzi F, Correale C, Vetrano S, Fiorino G, Beltrán B, Marabita F, Locati M, Spinelli A, Nos P, et al. 2013. Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease. Clin Exp Immunol. 173(2):250–258. doi: 10.1111/cei.12104.
  • Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 139(3):485–498. doi: 10.1016/j.cell.2009.09.033.
  • Iwauchi M, Horigome A, Ishikawa K, Mikuni A, Nakano M, Xiao JZ, Odamaki T, Hironaka S. 2019. Relationship between oral and gut microbiota in elderly people. Immun Inflamm Dis. 7(3):229–236. doi: 10.1002/iid3.266.
  • Jain U, Otley AR, Van Limbergen J, Stadnyk AW. 2014. The complement system in inflammatory bowel disease. Inflamm Bowel Dis. 20(9):1628–1637. doi: 10.1097/MIB.0000000000000056.
  • James JP, Riis LB, Malham M, Høgdall E, Langholz E, Nielsen BS. 2020. MicroRNA biomarkers in IBD-differential diagnosis and prediction of colitis-associated cancer. Int J Mol Sci. 21(21):7893. doi: 10.3390/ijms21217893.
  • Jeong HJ, Chung HS, Lee BR, Kim SJ, Yoo SJ, Hong SH, Kim HM. 2003. Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxamine-stimulated HMC-1 cells. Biochem Biophys Res Commun. 306(4):805–811. doi: 10.1016/s0006-291x(03)01073-8.
  • Ji Y, Li X, Zhu Y, Li N, Zhang N, Niu M. 2018. Faecal microRNA as a biomarker of the activity and prognosis of inflammatory bowel diseases. Biochem Biophys Res Commun. 503(4):2443–2450. doi: 10.1016/j.bbrc.2018.06.174.
  • Jia L, Han N, Du J, Guo L, Luo Z, Liu Y. 2019. Pathogenesis of important virulence factors of Porphyromonas gingivalis via toll-like receptors. Front Cell Infect Microbiol. 9:262. doi: 10.3389/fcimb.2019.00262.
  • Jia L, Wu R, Han N, Fu J, Luo Z, Guo L, Su Y, Du J, Liu Y. 2020. Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2. Clin Transl Immunology. 9(11):e1213. doi: 10.1002/cti2.1213.
  • Johnson GB, Brunn GJ, Kodaira Y, Platt JL. 2002. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol. 168(10):5233–5239. doi: 10.4049/jimmunol.168.10.5233.
  • Kalea AZ, Hoteit R, Suvan J, Lovering RC, Palmen J, Cooper JA, Khodiyar VK, Harrington Z, Humphries SE, D’Aiuto F. 2015. Upregulation of gingival tissue miR-200b in obese periodontitis subjects. J Dent Res. 94(3 Suppl):59S–69S. doi: 10.1177/0022034514568197.
  • Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, Kawashima T, Nanakin A, Sawabu T, Uenoyama Y, et al. 2004. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 23(28):4921–4929. doi: 10.1038/sj.onc.1207606.
  • Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, et al. 2017. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 5(1):10. doi: 10.1186/s40168-016-0225-7.
  • Kato S, Ochiai M, Sakurada T, Ohno S, Miyamoto K, Sagara M, Ito M, Takeuchi K, Imaki J, Itoh K, et al. 2008. Increased expression of long pentraxin PTX3 in inflammatory bowel diseases. Dig Dis Sci. 53(7):1910–1916. doi: 10.1007/s10620-007-0075-z.
  • Kato T, Yamazaki K, Nakajima M, Date Y, Kikuchi J, Hase K, Ohno H, Yamazaki K. 2018. Oral Administration of Porphyromonas gingivalis Alters the Gut Microbiome and Serum Metabolome. mSphere. 3(5):e00460-18. doi: 10.1128/mSphere.00460-18.
  • Kaur G, Grover V, Bhaskar N, Kaur RK, Jain A. 2018. Periodontal Infectogenomics. Inflamm Regen. 38(1):8. doi: 10.1186/s41232-018-0065-x.
  • Kawasaki T, Kawai T. 2014. Toll-like receptor signaling pathways. Front Immunol. 5:461. doi: 10.3389/fimmu.2014.00461.
  • Kempski J, Brockmann L, Gagliani N, Huber S. 2017. TH17 Cell and epithelial cell crosstalk during inflammatory bowel disease and carcinogenesis. Front Immunol. 8:1373. doi: 10.3389/fimmu.2017.01373.
  • Kharaghani AA, Harzandi N, Khorsand B, Rajabnia M, Kharaghani AA, Houri H. 2023. High prevalence of Mucosa-Associated extended-spectrum β-Lactamase-producing Escherichia coli and Klebsiella pneumoniae among Iranain patients with inflammatory bowel disease (IBD). Ann Clin Microbiol Antimicrob. 22(1):86. ; 5. doi: 10.1186/s12941-023-00630-x.
  • Khorsand B, Asadzadeh Aghdaei H, Nazemalhosseini-Mojarad E, Nadalian B, Nadalian B, Houri H. 2022. Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets. Front Cell Infect Microbiol. 12:1015890. doi: 10.3389/fcimb.2022.1015890.
  • Kim S, Park MH, Song YR, Na HS, Chung J. 2016. Aggregatibacter actinomycetemcomitans-Induced AIM2 Inflammasome Activation Is Suppressed by Xylitol in Differentiated THP-1 Macrophages. J Periodontol. 87(6):e116-26–e126. doi: 10.1902/jop.2016.150477.
  • Kirk KF, Nielsen HL, Thorlacius-Ussing O, Nielsen H. 2016. Optimized cultivation of Campylobacter concisus from gut mucosal biopsies in inflammatory bowel disease. Gut Pathog. 8(1):27. doi: 10.1186/s13099-016-0111-7.
  • Kitamoto S, Nagao-Kitamoto H, Jiao Y, Gillilland MG, 3rd, Hayashi A, Imai J, Sugihara K, Miyoshi M, Brazil JC, Kuffa P, et al. 2020. The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis. Cell. 182(2):447–462.e14. doi: 10.1016/j.cell.2020.05.048.
  • Kong J, Yuan X, Wang J, Liu Y, Sun W, Gu B, Lan Z, Gao S. 2021. Frequencies of Porphyromonas gingivalis detection in oral-digestive tract tumors. Pathol Oncol Res. 27:628942. 1 Retraction in: Pathol Oncol Res. 2023 Dec 19;29:1611616. doi: 10.3389/pore.2021.628942.
  • Koren O, Spor A, Felin J, Fåk F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, et al. 2011. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A. 108 Suppl 1(Suppl 1):4592–4598. doi: 10.1073/pnas.1011383107.
  • Krongbaramee T, Zhu M, Qian Q, Zhang Z, Eliason S, Shu Y, Qian F, Akkouch A, Su D, Amendt BA, et al. 2021. Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice. Mol Ther Nucleic Acids. 23:1204–1216. doi: 10.1016/j.omtn.2021.01.030.
  • Kubinak JL, Petersen C, Stephens WZ, Soto R, Bake E, O’Connell RM, Round JL. 2015. MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host Microbe. 17(2):153–163. doi: 10.1016/j.chom.2014.12.009.
  • Ku T, Pandey R, Chauhan NS. 2020. Hypoxia inducible factor-1α: the curator of gut homeostasis. Front Cell Infect Microbiol. 10:227. doi: 10.3389/fcimb.2020.00227.
  • Lassègue B, Sorescu D, Szöcs K, Yin Q, Akers M, Zhang Y, Grant SL, Lambeth JD, Griendling KK. 2001. Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res. 88(9):888–894. doi: 10.1161/hh0901.090299.
  • Laufer J, Oren R, Goldberg I, Horwitz A, Kopolovic J, Chowers Y, Passwell JH. 2000. Cellular localization of complement C3 and C4 transcripts in intestinal specimens from patients with Crohn’s disease. Clin Exp Immunol. 120(1):30–37. doi: 10.1046/j.1365-2249.2000.01168.x.
  • Lazaridis LD, Pistiki A, Giamarellos-Bourboulis EJ, Georgitsi M, Damoraki G, Polymeros D, Dimitriadis GD, Triantafyllou K. 2017. Activation of NLRP3 inflammasome in inflammatory bowel disease: differences between crohn’s disease and ulcerative colitis. Dig Dis Sci. 62(9):2348–2356. doi: 10.1007/s10620-017-4609-8.
  • Leal RF, Planell N, Kajekar R, Lozano JJ, Ordás I, Dotti I, Esteller M, Masamunt MC, Par H, Ricart E, et al. 2015. Identification of inflammatory mediators in patients with Crohn’s disease unresponsive to anti-TNFα therapy. Gut. 64(2):233–242. doi: 10.1136/gutjnl-2013-306518.
  • Lee YH, Na HS, Jeong SY, Jeong SH, Park HR, Chung J. 2011. Comparison of inflammatory microRNA expression in healthy and periodontitis tissues. Biocell. 35(2):43–49. 22128589.
  • Lembeck F, Donnerer J, Tsuchiya M, Nagahisa A. 1992. The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol. 105(3):527–530. doi: 10.1111/j.1476-5381.1992.tb09013.x.
  • Li B, Ge Y, Cheng L, Zeng B, Yu J, Peng X, Zhao J, Li W, Ren B, Li M, et al. 2019. Oral bacteria colonize and compete with gut microbiota in gnotobiotic mice. Int J Oral Sci. 11(1):10. doi: 10.1038/s41368-018-0043-9.
  • Li M, Zhao J, Cao M, Liu R, Chen G, Li S, Xie Y, Xie J, Cheng Y, Huang L, et al. 2020. Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells. Biol Res. 53(1):12. doi: 10.1186/s40659-020-00279-2.
  • Li W, Xu J, Zhang R, Li Y, Wang J, Zhang X, Lin L. 2021. Is periodontal disease a risk indicator for colorectal cancer? A systematic review and meta-analysis. J Clin Periodontol. 48(3):336–347. doi: 10.1111/jcpe.13402.
  • Li X, Kolltveit KM, Tronstad L, Olsen I. 2000. Systemic diseases caused by oral infection. Clin Microbiol Rev. 13(4):547–558. doi: 10.1128/CMR.13.4.547.
  • Li ZJ, Gou HZ, Zhang YL, Song XJ, Zhang L. 2022. Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value. World J Gastroenterol. 28(44):6213–6229. doi: 10.3748/wjg.v28.i44.6213.
  • Liang Q, Chiu J, Chen Y, Huang Y, Higashimori A, Fang J, Brim H, Ashktorab H, Ng SC, Ng SSM, et al. 2017. Fecal bacteria act as novel biomarkers for noninvasive diagnosis of colorectal cancer. Clin Cancer Res. 23(8):2061–2070. doi: 10.1158/1078-0432.CCR-16-1599.
  • Liang S, Krauss JL, Domon H, McIntosh ML, Hosur KB, Qu H, Li F, Tzekou A, Lambris JD, Hajishengallis G. 2011. The C5a receptor impairs IL-12-dependent clearance of Porphyromonas gingivalis and is required for induction of periodontal bone loss. J Immunol. 186(2):869–877. doi: 10.4049/jimmunol.1003252.
  • Linden GJ, McKinnell J, Shaw C, Lundy FT. 1997. Substance P and neurokinin A in gingival crevicular fluid in periodontal health and disease. J Clin Periodontol. 24(11):799–803. doi: 10.1111/j.1600-051x.1997.tb01192.x.
  • Littman DR, Rudensky AY. 2010. Th17 and regulatory T cells in mediating and restraining inflammation. Cell. 140(6):845–858. doi: 10.1016/j.cell.2010.02.021.
  • Liu H, Hong XL, Sun TT, Huang XW, Wang JL, Xiong H. 2020. Fusobacterium nucleatum exacerbates colitis by damaging epithelial barriers and inducing aberrant inflammation. J Dig Dis. 21(7):385–398. doi: 10.1111/1751-2980.12909.
  • Liu L, Dong Y, Ye M, Jin S, Yang J, Joosse ME, Sun Y, Zhang J, Lazarev M, Brant SR, et al. 2017. The pathogenic role of NLRP3 inflammasome activation in inflammatory bowel diseases of both mice and humans. J Crohns Colitis. 11(6):737–750. doi: 10.1093/ecco-jcc/jjw219.
  • Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, Bry L, Comstock LE, Gandhi R, Weiner HL. 2016. The host shapes the gut microbiota via fecal MicroRNA. Cell Host Microbe. 19(1):32–43. doi: 10.1016/j.chom.2015.12.005.
  • Liu Y, Yin H, Zhao M, Lu Q. 2014. TLR2 and TLR4 in autoimmune diseases: a comprehensive review. Clin Rev Allergy Immunol. 47(2):136–147. doi: 10.1007/s12016-013-8402-y.
  • Lockhart PB, Brennan MT, Thornhill M, Michalowicz BS, Noll J, Bahrani-Mougeot FK, Sasser HC. 2009. Poor oral hygiene as a risk factor for infective endocarditis-related bacteremia. J Am Dent Assoc. 140(10):1238–1244. doi: 10.14219/jada.archive.2009.0046.
  • Loh G, Blaut M. 2012. Role of commensal gut bacteria in inflammatory bowel diseases. Gut Microbes. 3(6):544–555. doi: 10.4161/gmic.22156.
  • Lourenςo TGB, Spencer SJ, Alm EJ, Colombo APV. 2018. Defining the gut microbiota in individuals with periodontal diseases: an exploratory study. J Oral Microbiol. 10(1):1487741. doi: 10.1080/20002297.2018.1487741.
  • Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al. 2005. MicroRNA expression profiles classify human cancers. Nature. 435(7043):834–838. doi: 10.1038/nature03702.
  • Lu Y, Li X, Liu S, Zhang Y, Zhang D. 2018. Toll-like receptors and inflammatory bowel disease. Front Immunol. 9:72. doi: 10.3389/fimmu.2018.00072.
  • Lv L, Jiang H, Chen X, Wang Q, Wang K, Ye J, Li Y, Fang D, Lu Y, Yang L, et al. 2021. The salivary microbiota of patients with primary biliary cholangitis is distinctive and pathogenic. Front Immunol. 12:713647. doi: 10.3389/fimmu.2021.713647.
  • Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, Balk SP, O’Shea D, O’Farrelly C, Exley MA. 2012. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity. 37(3):574–587. doi: 10.1016/j.immuni.2012.06.016.
  • Lyte M. 2011. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays. 33(8):574–581. doi: 10.1002/bies.201100024.
  • Ma L, Pang C, Yan C, Chen J, Wang X, Hui J, Zhou L, Zhang X. 2023. Effect of lemon essential oil on halitosis. Oral Dis. 29(4):1845–1854. doi: 10.1111/odi.14140.
  • Maisonneuve P, A S, Lowenfels AB. 2017. Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis. Ann Oncol. 28(5):985–995. doi: 10.1093/annonc/mdx019.
  • Malham M, James J, Jakobsen C, Høgdall E, Holmstroem K, Wewer V, Nielsen BS, Riis L. 2021. The mucosal microRNA profile relates to age and severity of disease in patients with ulcerative colitis. Gastroenterology. 160(3):S15. doi: 10.1053/j.gastro.2021.01.065.
  • Mangerich A, Dedon PC, Fox JG, Tannenbaum SR, Wogan GN. 2013. Chemistry meets biology in colitis-associated carcinogenesis. Free Radic Res. 47(11):958–986. doi: 10.3109/10715762.2013.832239.
  • Martinon F, Tschopp J. 2007. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 14(1):10–22. doi: 10.1038/sj.cdd.4402038.
  • McBee ME, Chionh YH, Sharaf ML, Ho P, Cai MW, Dedon PC. 2017. Production of superoxide in bacteria is stress- and cell state-dependent: a gating-optimized flow cytometry method that minimizes ros measurement artifacts with fluorescent dyes. Front Microbiol. 8:459. doi: 10.3389/fmicb.2017.00459.
  • McCall SH, Sahraei M, Young AB, Worley CS, Duncan JA, Ting JP, Marriott I. 2008. Osteoblasts express NLRP3, a nucleotide-binding domain and leucine-rich repeat region containing receptor implicated in bacterially induced cell death. J Bone Miner Res. 23(1):30–40. doi: 10.1359/jbmr.071002.
  • McClain CJ, Barve S, Deaciuc I, Kugelmas M, Hill D. 1999. Cytokines in alcoholic liver disease. Semin Liver Dis. 19(2):205–219. doi: 10.1055/s-2007-1007110.
  • McKenna LB, Schug J, Vourekas A, McKenna JB, Bramswig NC, Friedman JR, Kaestner KH. 2010. MicroRNAs control intestinal epithelial differentiation, architecture, and barrier function. Gastroenterology. 139(5):1654–1664, 1664.e1. doi: 10.1053/j.gastro.2010.07.040.
  • Medani M, Collins D, Docherty NG, Baird AW, O’Connell PR, Winter DC. 2011. Emerging role of hydrogen sulfide in colonic physiology and pathophysiology. Inflamm Bowel Dis. 17(7):1620–1625. doi: 10.1002/ibd.21528.
  • Medzhitov R, Preston-Hurlburt P, Janeway CA.Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 388(6640):394–397. doi: 10.1038/41131.
  • Megson E, Fitzsimmons T, Dharmapatni K, Bartold PM. 2010. C-reactive protein in gingival crevicular fluid may be indicative of systemic inflammation. J Clin Periodontol. 37(9):797–804. doi: 10.1111/j.1600-051X.2010.01603.x.
  • Michaud DS, Izard J, Wilhelm-Benartzi CS, You DH, Grote VA, Tjønneland A, Dahm CC, Overvad K, Jenab M, Fedirko V, et al. 2013. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut. 62(12):1764–1770. doi: 10.1136/gutjnl-2012-303006.
  • Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, Yang J, Dou R, Masugi Y, Song M, et al. 2016. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 65(12):1973–1980. doi: 10.1136/gutjnl-2015-310101.
  • Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, et al. 2015. Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget. 6(9):7209–7220. doi: 10.18632/oncotarget.3109.
  • Miura K, Ohnishi H. 2014. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 20(23):7381–7391. doi: 10.3748/wjg.v20.i23.7381.
  • Morton AM, Sefik E, Upadhyay R, Weissleder R, Benoist C, Mathis D. 2014. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proc Natl Acad Sci U S A. 111(18):6696–6701. doi: 10.1073/pnas.1405634111.
  • Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, Nares S, Osorio M, Wahl SM. 2012. Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis. J Autoimmun. 39(4):294–303. doi: 10.1016/j.jaut.2012.03.003.
  • Nakahara T, Hyogo H, Ono A, Nagaoki Y, Kawaoka T, Miki D, Tsuge M, Hiraga N, Hayes CN, Hiramatsu A, et al. 2018. Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease. J Gastroenterol. 53(2):269–280. doi: 10.1007/s00535-017-1368-4.
  • Nakajima M, Arimatsu K, Kato T, Matsuda Y, Minagawa T, Takahashi N, Ohno H, Yamazaki K. 2015. Oral administration of P. gingivalis induces dysbiosis of gut microbiota and impaired barrier function leading to dissemination of enterobacteria to the liver. PLoS One. 10(7):e0134234. doi: 10.1371/journal.pone.0134234.
  • Nandy SK, Bapat PM, Venkatesh KV. 2007. Sporulating bacteria prefers predation to cannibalism in mixed cultures. FEBS Lett. 581(1):151–156. doi: 10.1016/j.febslet.2006.12.011.
  • Ng W, Tonzetich J. 1984. Effect of hydrogen sulfide and methyl mercaptan on the permeability of oral mucosa. J Dent Res. 63(7):994–997. doi: 10.1177/00220345840630071701.
  • Ni J, Huang R, Zhou H, Xu X, Li Y, Cao P, Zhong K, Ge M, Chen X, Hou B, et al. 2019. Analysis of the relationship between the degree of dysbiosis in gut microbiota and prognosis at different stages of primary hepatocellular carcinoma. Front Microbiol. 10:1458. doi: 10.3389/fmicb.2019.01458.
  • Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. 2012. Host-gut microbiota metabolic interactions. Science. 336(6086):1262–1267. doi: 10.1126/science.1223813.
  • O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. 2007. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 104(5):1604–1609. doi: 10.1073/pnas.0610731104.
  • Ogata Y, Matsui S, Kato A, Zhou L, Nakayama Y, Takai H. 2014. MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients. J Oral Sci. 56(4):253–260. doi: 10.2334/josnusd.56.253.
  • Ozdemir A, Mas MR, Sahin S, Sağlamkaya U, Ateşkan U. 2001. Detection of Helicobacter pylori colonization in dental plaques and tongue scrapings of patients with chronic gastritis. Quintessence Int. 32(2):131–134.
  • Oztürk A, Yildiz L. 2011. Expression of transient receptor potential vanilloid receptor 1 and toll-like receptor 4 in aggressive periodontitis and in chronic periodontitis. J Periodontal Res. 46(4):475–482. doi: 10.1111/j.1600-0765.2011.01363.x.
  • Pacher P, Beckman JS, Liaudet L. 2007. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 87(1):315–424. doi: 10.1152/physrev.00029.2006.
  • Papadopoulos G, Berland R, Sunkavalli A, Coats SR, Darveau RP, Genco CA. 2021. Microbial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function. Infect Immun. 89(2):e00335-20. doi: 10.1128/IAI.00335-20.
  • Parahitiyawa NB, Jin LJ, Leung WK, Yam WC, Samaranayake LP. 2009. Microbiology of odontogenic bacteremia: beyond endocarditis. Clin Microbiol Rev. 22(1):46–64. Erratum in: Clin Microbiol Rev. 2009 Apr;22(2):386. doi: 10.1128/CMR.00028-08.
  • Paraskevi A, Theodoropoulos G, Papaconstantinou I, Mantzaris G, Nikiteas N, Gazouli M. 2012. Circulating MicroRNA in inflammatory bowel disease. J Crohns Colitis. 6(9):900–904. doi: 10.1016/j.crohns.2012.02.006.
  • Park JH, Peyrin-Biroulet L, Eisenhut M, Shin JI. 2017. IBD immunopathogenesis: A comprehensive review of inflammatory molecules. Autoimmun Rev. 16(4):416–426. doi: 10.1016/j.autrev.2017.02.013.
  • Peck BC, Mah AT, Pitman WA, Ding S, Lund PK, Sethupathy P. 2017. Functional transcriptomics in diverse intestinal epithelial cell types reveals robust MicroRNA sensitivity in intestinal stem cells to microbial status. J Biol Chem. 292(7):2586–2600. doi: 10.1074/jbc.M116.770099.
  • Peng X, Cheng L, You Y, Tang C, Ren B, Li Y, Xu X, Zhou X. 2022. Oral microbiota in human systematic diseases. Int J Oral Sci. 14(1):14. doi: 10.1038/s41368-022-00163-7.
  • Perri R, Nares S, Zhang S, Barros SP, Offenbacher S. 2012. MicroRNA modulation in obesity and periodontitis. J Dent Res. 91(1):33–38. doi: 10.1177/0022034511425045.
  • Persson GR, Pettersson T, Ohlsson O, Renvert S. 2005. High‐sensitivity serum C‐reactive protein levels in subjects with or without myocardial infarction or periodontitis. J Clin Periodontol. 32(3):219–224. doi: 10.1111/j.1600-051X.2005.00648.x.
  • Peters BA, Wu J, Pei Z, Yang L, Purdue MP, Freedman ND, Jacobs EJ, Gapstur SM, Hayes RB, Ahn J. 2017. Oral microbiome composition reflects prospective risk for esophageal cancers. Cancer Res. 77(23):6777–6787. doi: 10.1158/0008-5472.CAN-17-1296.
  • Pham BN, Mosnier JF, Durand F, Scoazec JY, Chazouilleres O, Degos F, Belghiti J, Degott C, Benhamou JP, Erlinger S. 1995. Immunostaining for membrane attack complex of complement is related to cell necrosis in fulminant and acute hepatitis. Gastroenterology. 108(2):495–504. doi: 10.1016/0016-5085(95)90079-9.
  • Pirola CJ, Fernández Gianotti T, Castaño GO, Mallardi P, San Martino J, Mora Gonzalez Lopez Ledesma M, Flichman D, Mirshahi F, Sanyal AJ, Sookoian S. 2015. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut. 64(5):800–812. doi: 10.1136/gutjnl-2014-306996.
  • Pitcher MC, Cummings JH. 1996. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut. 39(1):1–4. doi: 10.1136/gut.39.1.1.
  • Pohl JF, Melin-Aldana H, Sabla G, Degen JL, Bezerra JA. 2001. Plasminogen deficiency leads to impaired lobular reorganization and matrix accumulation after chronic liver injury. Am J Pathol. 159(6):2179–2186. doi: 10.1016/S0002-9440(10)63069-6.
  • Polak D, Shapira L, Weiss EI, Houri-Haddad Y. 2012. The role of coaggregation between Porphyromonas gingivalis and Fusobacterium nucleatum on the host response to mixed infection. J Clin Periodontol. 39(7):617–625. doi: 10.1111/j.1600-051X.2012.01889.x.
  • Polepalle T, Moogala S, Boggarapu S, Pesala DS, Palagi FB. 2015. Acute phase proteins and their role in periodontitis: a review. J Clin Diagn Res. 9(11):ZE01–5. doi: 10.7860/JCDR/2015/15692.6728.
  • Pradeep AR, Raj S, Aruna G, Chowdhry S. 2009. Gingival crevicular fluid and plasma levels of neuropeptide Substance-P in periodontal health, disease and after nonsurgical therapy. J Periodontal Res. 44(2):232–237. doi: 10.1111/j.1600-0765.2008.01138.x.
  • Qi Y, Zang SQ, Wei J, Yu HC, Yang Z, Wu HM, Kang Y, Tao H, Yang MF, Jin L, et al. 2021. High-throughput sequencing provides insights into oral microbiota dysbiosis in association with inflammatory bowel disease. Genomics. 113(1):664–676. doi: 10.1016/j.ygeno.2020.09.063.
  • Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, Guo J, Le Chatelier E, Yao J, Wu L, et al. 2014. Alterations of the human gut microbiome in liver cirrhosis. Nature. 513(7516):59–64. doi: 10.1038/nature13568.
  • Ramakrishna BS, Roberts-Thomson IC, Pannall PR, Roediger WE. 1991. Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis. Gut. 32(1):46–49. doi: 10.1136/gut.32.1.46.
  • Rao RK, Baker RD, Baker SS, Gupta A, Holycross M. 1997. Oxidant-induced disruption of intestinal epithelial barrier function: role of protein tyrosine phosphorylation. Am J Physiol. 273(4):G812–23. doi: 10.1152/ajpgi.1997.273.4.G812.
  • Ray K. 2020. The oral-gut axis in IBD. Nat Rev Gastroenterol Hepatol. 17(9):532–532. doi: 10.1038/s41575-020-0346-0.
  • Read E, Curtis MA, Neves JF. 2021. The role of oral bacteria in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 18(10):731–742. doi: 10.1038/s41575-021-00488-4.
  • Ren Z, Li A, Jiang J, Zhou L, Yu Z, Lu H, Xie H, Chen X, Shao L, Zhang R, et al. 2019. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut. 68(6):1014–1023. doi: 10.1136/gutjnl-2017-315084.
  • Rengara S, Vivio EE, Parkes M, Peterson DA, Roberson EDO, Newberry RD, Ciorba MA, Hsieh CS. 2020. Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. Gut Microbes. 11(3):405–420. doi: 10.1080/19490976.2019.1626683.
  • Richens ER, Thorp CM, Bland PW, Hall ND. 1982. Circulating immune complexes in Crohn’s disease. Their characterization and interrelationship with components of the complement system. Dig Dis Sci. 27(2):129–138. doi: 10.1007/BF01311706.
  • Rismo R, Olsen T, Cui G, Christiansen I, Florholmen J, Goll R. 2012. Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis. Scand J Gastroenterol. 47(5):538–547. doi: 10.3109/00365521.2012.667146.
  • Rodrigues PM, Perugorria MJ, Santos-Laso A, Bujanda L, Beuers U, Banales JM. 2018. Primary biliary cholangitis: A tale of epigenetically-induced secretory failure? J Hepatol. 69(6):1371–1383. doi: 10.1016/j.jhep.2018.08.020.
  • Rodriguez Herrero E, Boon N, Pauwels M, Bernaerts K, Slomka V, Quirynen M, Teughels W. 2017. Necrotrophic growth of periodontopathogens is a novel virulence factor in oral biofilms. Sci Rep. 7(1):1107. doi: 10.1038/s41598-017-01239-9.
  • Rodríguez-Nogales A, Algieri F, Garrido-Mesa J, Vezza T, Utrilla MP, Chueca N, Garcia F, Olivares M, Rodríguez-Cabezas ME, Gálvez J. 2017. Differential intestinal anti-inflammatory effects of Lactobacillus fermentum and Lactobacillus salivarius in DSS mouse colitis: impact on microRNAs expression and microbiota composition. Mol Nutr Food Res. 61(11) doi: 10.1002/mnfr.201700144.
  • Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Schölmerich J, Gross V. 1998. Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology. 115(2):357–369. doi: 10.1016/s0016-5085(98)70202-1.
  • Rubin DT, Uluscu O, Sederman R. 2012. Response to biologic therapy in Crohn’s disease is improved with early treatment: an analysis of health claims data. Inflamm Bowel Dis. 18(12):2225–2231. doi: 10.1002/ibd.22925.
  • Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. 2013. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe. 14(2):195–206. doi: 10.1016/j.chom.2013.07.012.
  • Sahingur SE, Sharma A, Genco RJ, De Nardin E. 2003. Association of increased levels of fibrinogen and the -455G/A fibrinogen gene polymorphism with chronic periodontitis. J Periodontol. 74(3):329–337. doi: 10.1902/jop.2003.74.3.329.
  • Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho JK. 2008. Role of cytokines in inflammatory bowel disease. World J Gastroenterol. 14(27):4280–4288. doi: 10.3748/wjg.14.4280.
  • Sasaki M, Joh T. 2007. Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr. 40(1):1–12. doi: 10.3164/jcbn.40.1.
  • Savchenko AS, Inoue A, Ohashi R, Jiang S, Hasegawa G, Tanaka T, Hamakubo T, Kodama T, Aoyagi Y, Ushiki T, et al. 2011. Long pentraxin 3 (PTX3) expression and release by neutrophils in vitro and in ulcerative colitis. Pathol Int. 61(5):290–297. doi: 10.1111/j.1440-1827.2011.02651.x.
  • Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjøt L, Wiuf C, Sørensen FJ, Kruhøffer M, Laurberg S, et al. 2008. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 68(15):6416–6424. doi: 10.1158/0008-5472.CAN-07-6110.
  • Schieferdecker HL, Rothermel E, Timmermann A, Götze O, Jungermann K. 1997. Anaphylatoxin C5a receptor mRNA is strongly expressed in Kupffer and stellate cells and weakly in sinusoidal endothelial cells but not in hepatocytes of normal rat liver. FEBS Lett. 406(3):305–309. doi: 10.1016/s0014-5793(97)00292-5.
  • Schieferdecker HL, Schlaf G, Jungermann K, Götze O. 2001. Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells. Int Immunopharmacol. 1(3):469–481. doi: 10.1016/s1567-5769(00)00038-2.
  • Schmidt TS, Hayward MR, Coelho LP, Li SS, Costea PI, Voigt AY, Wirbel J, Maistrenko OM, Alves RJ, Bergsten E, et al. 2019. Extensive transmission of microbes along the ­gastrointestinal tract. Elife. 8:e42693. doi: 10.7554/eLife.42693.
  • Scholz A, Heinze S, Detjen KM, Peters M, Welzel M, Hauff P, Schirner M, Wiedenmann B, Rosewicz S. 2003. Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology. 125(3):891–905. doi: 10.1016/s0016-5085(03)01064-3.
  • Schönauen K, Le N, von Arnim U, Schulz C, Malfertheiner P, Link A. 2018. Circulating and fecal microRNAs as biomarkers for inflammatory bowel diseases. Inflamm Bowel Dis. 24(7):1547–1557. doi: 10.1093/ibd/izy046.
  • Segata N, Haake SK, Mannon P, Lemon KP, Waldron L, Gevers D, Huttenhower C, Izard J. 2012. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 13(6):R42. doi: 10.1186/gb-2012-13-6-r42.
  • Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, Pfennig S, Jürgens M, Schmechel S, Konrad A, et al. 2008. Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis. 14(4):437–445. doi: 10.1002/ibd.20339.
  • Seki E, Brenner DA. 2008. Toll-like receptors and adaptor molecules in liver disease: update. Hepatology. 48(1):322–335. doi: 10.1002/hep.22306.
  • Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, Schwabe RF. 2007. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 13(11):1324–1332. doi: 10.1038/nm1663.
  • Seo SU, Kamada N, Muñoz-Planillo R, Kim YG, Kim D, Koizumi Y, Hasegawa M, Himpsl SD, Browne HP, Lawley TD, et al. 2015. Distinct commensals induce interleukin-1β via NLRP3 inflammasome in inflammatory monocytes to promote intestinal inflammation in response to injury. Immunity. 42(4):744–755. doi: 10.1016/j.immuni.2015.03.004.
  • Shale M, Schiering C, Powrie F. 2013. CD4(+) T-cell subsets in intestinal inflammation. Immunol Rev. 252(1):164–182. doi: 10.1111/imr.12039.
  • She YY, Kong XB, Ge YP, Liu ZY, Chen JY, Jiang JW, Jiang HB, Fang SL. 2020. Periodontitis and inflammatory bowel disease: a meta-analysis. BMC Oral Health. 20(1):67. doi: 10.1186/s12903-020-1053-5.
  • Shi T, Xie Y, Fu Y, Zhou Q, Ma Z, Ma J, Huang Z, Zhang J, Chen J. 2017. The signaling axis of microRNA-31/interleukin-25 regulates Th1/Th17-mediated inflammation response in colitis. Mucosal Immunol. 10(4):983–995. doi: 10.1038/mi.2016.102.
  • Shojaee M, Fereydooni Golpasha M, Maliji G, Bijani A, Aghajanpour Mir SM, Mousavi Kani SN. 2013. C - reactive protein levels in patients with periodontal disease and normal subjects. Int J Mol Cell Med. 2(3):151–155.
  • Sina C, Kemper C, Derer S. 2018. The intestinal complement system in inflammatory bowel disease: Shaping intestinal barrier function. Semin Immunol. 37:66–73. doi: 10.1016/j.smim.2018.02.008.
  • Slade GD, Offenbacher S, Beck JD, Heiss G, Pankow JS. 2000. Acute-phase inflammatory response to periodontal disease in the US population. J Dent Res. 79(1):49–57. doi: 10.1177/00220345000790010701.
  • Slots J. 2019. Focal infection of periodontal origin. Periodontol 2000. 79(1):233–235. doi: 10.1111/prd.12258.
  • Sorensen NS, Tegtmeier C, Andresen LO, Piñeiro M, Toussaint MJ, Campbell FM, Lampreave F, Heegaard PM. 2006. The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis. Vet Immunol Immunopathol. 113(1-2):157–168. doi: 10.1016/j.vetimm.2006.04.008.
  • Stoecklin-Wasmer C, Guarnieri P, Celenti R, Demmer RT, Kebschull M, Papapanou PN. 2012. MicroRNAs and their target genes in gingival tissues. J Dent Res. 91(10):934–940. doi: 10.1177/0022034512456551.
  • Strober W. 2010. Inside the microbial and immune labyrinth: gut microbes: friends or fiends? Nat Med. 16(11):1195–1197. doi: 10.1038/nm1110-1195.
  • Stummer N, Feichtinger RG, Weghuber D, Kofler B, Schneider AM. 2023. Role of hydrogen sulfide in inflammatory bowel disease. Antioxidants (Basel). 12(8):1570. doi: 10.3390/antiox12081570.
  • Sugihara T, Kobori A, Imaeda H, Tsujikawa T, Amagase K, Takeuchi K, Fujiyama Y, Andoh A. 2010. The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol. 160(3):386–393. doi: 10.1111/j.1365-2249.2010.04093.x.
  • Surrenti C, Renzi D, Garcea MR, Surrenti E, Salvadori G. 1993. Colonic vasoactive intestinal polypeptide in ulcerative colitis. J Physiol Paris. 87(5):307–311. doi: 10.1016/0928-4257(93)90037-t.
  • Swidsinski A, Schlien P, Pernthaler A, Gottschalk U, Bärlehner E, Decker G, Swidsinski S, Strassburg J, Loening-Baucke V, Hoffmann U, et al. 2005. Bacterial biofilm within diseased pancreatic and biliary tracts. Gut. 54(3):388–395. doi: 10.1136/gut.2004.043059.
  • Swindle EJ, Metcalfe DD. 2007. The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes. Immunol Rev. 217(1):186–205. doi: 10.1111/j.1600-065X.2007.00513.x.
  • Takuma R, Morozumi T, Yamamoto Y, Kobayashi T, Matsui T, Yoneda M, Kessoku T, Nogami A, Tamura M, Kamata Y, et al. 2023. Association between non-alcoholic steatohepatitis-related hepatocellular carcinoma and periodontopathic bacteria: a cross-sectional pilot study. Applied Sciences. 13(6):3893. 19doi: 10.3390/app13063893.
  • Teles R, Teles F, Frias-Lopez J, Paster B, Haffajee A. 2013. Lessons learned and unlearned in periodontal microbiology. Periodontol 2000. 62(1):95–162. doi: 10.1111/prd.12010.
  • Temmerman R, Vervaeren H, Noseda B, Boon N, Verstraete W. 2006. Necrotrophic growth of Legionella pneumophila. Appl Environ Microbiol. 72(6):4323–4328. doi: 10.1128/AEM.00070-06.
  • Thomas B, Rao A, Prasad BR, Kumari S. 2014. Serum levels of antioxidants and superoxide dismutase in periodontitis patients with diabetes type 2. J Indian Soc Periodontol. 18(4):451–455. doi: 10.4103/0972-124X.138686.
  • Thorlacius-Ussing G, Schnack Nielsen B, Andersen V, Holmstrøm K, Pedersen AE. 2017. Expression and localization of miR-21 and miR-126 in mucosal tissue from patients with inflammatory bowel disease. Inflamm Bowel Dis. 23(5):739–752. doi: 10.1097/MIB.0000000000001086.
  • Tian Y, Xu J, Li Y, Zhao R, Du S, Lv C, Wu W, Liu R, Sheng X, Song Y, et al. 2019. MicroRNA-31 reduces inflammatory signaling and promotes regeneration in colon epithelium, and delivery of mimics in microspheres reduces colitis in mice. Gastroenterology. 156(8):2281–2296.e6. doi: 10.1053/j.gastro.2019.02.023.
  • Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, Flavell RA, Girardin SE, Godzik A, Harton JA, et al. 2008. The NLR gene family: a standard nomenclature. Immunity. 28(3):285–287. doi: 10.1016/j.immuni.2008.02.005.
  • Toubal A, Kiaf B, Beaudoin L, Cagninacci L, Rhimi M, Fruchet B, da Silva J, Corbett AJ, Simoni Y, Lantz O, et al. 2020. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity. Nat Commun. 11(1):3755. doi: 10.1038/s41467-020-17307-0.
  • Tsareva SA, Moriggl R, Corvinus FM, Wiederanders B, Schütz A, Kovacic B, Friedrich K. 2007. Signal transducer and activator of transcription 3 activation promotes invasive growth of colon carcinomas through matrix metalloproteinase induction. Neoplasia. 9(4):279–291. doi: 10.1593/neo.06820.
  • Ueki T, Mizuno M, Uesu T, Kiso T, Nasu J, Inaba T, Kihara Y, Matsuoka Y, Okada H, Fujita T, et al. 1996. Distribution of activated complement, C3b, and its degraded fragments, iC3b/C3dg, in the colonic mucosa of ulcerative colitis (UC). Clin Exp Immunol. 104(2):286–292. doi: 10.1046/j.1365-2249.1996.17721.x.
  • Ugarova TP, Yakubenko VP. 2001. Recognition of fibrinogen by leukocyte integrins. Ann N Y Acad Sci. 936(1):368–385. doi: 10.1111/j.1749-6632.2001.tb03523.x.
  • Uhrig A, Banafsche R, Kremer M, Hegenbarth S, Hamann A, Neurath M, Gerken G, Limmer A, Knolle PA. 2005. Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver. J Leukoc Biol. 77(5):626–633. Erratum in: J Leukoc Biol. 2005 Jul;78(1):5A. doi: 10.1189/jlb.0604332.
  • van Deventer SJ. 1999. Review article: targeting TNF alpha as a key cytokine in the inflammatory processes of Crohn’s disease–the mechanisms of action of infliximab. Aliment Pharmacol Ther. 13 Suppl 4:3–8; discussion 38. doi: 10.1046/j.1365-2036.1999.00024.x.
  • Van Spaendonk H, Ceuleers H, Witters L, Patteet E, Joossens J, Augustyns K, Lambeir AM, De Meester I, De Man JG, De Winter BY. 2017. Regulation of intestinal permeability: the role of proteases. World J Gastroenterol. 23(12):2106–2123. doi: 10.3748/wjg.v23.i12.2106.
  • Visekruna A, Joeris T, Seidel D, Kroesen A, Loddenkemper C, Zeitz M, Kaufmann SH, Schmidt-Ullrich R, Steinhoff U. 2006. Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. J Clin Invest. 116(12):3195–3203. doi: 10.1172/JCI28804.
  • Volanakis JE, Kaplan MH. 1971. Specificity of C-reactive protein for choline phosphate residues of pneumococcal C-polysaccharide. Proc Soc Exp Biol Med. 136(2):612–614. doi: 10.3181/00379727-136-35323.
  • Vona R, Pallotta L, Cappelletti M, Severi C, Matarrese P. 2021. The impact of oxidative stress in human pathology: focus on gastrointestinal disorders. Antioxidants (Basel). 10(2):201. doi: 10.3390/antiox10020201.
  • Wang H, Chao K, Ng SC, Bai AH, Yu Q, Yu J, Li M, Cui Y, Chen M, Hu JF, et al. 2016. Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease. Genome Biol. 17(1):58. doi: 10.1186/s13059-016-0901-8.
  • Wang PL, Ohura K. 2002. Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. Crit Rev Oral Biol Med. 13(2):132–142. doi: 10.1177/154411130201300204.
  • Ward M, Eastwood MA. 1975. Serum C3 and C4 complement components in ulcerative colitis and Crohn’s disease. Digestion. 13(1-2):100–103. doi: 10.1159/000197698.
  • Warren RL, Freeman DJ, Pleasance S, Watson P, Moore RA, Cochrane K, Allen-Vercoe E, Holt RA. 2013. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome. 1(1):16. doi: 10.1186/2049-2618-1-16.
  • Weber CR, Turner JR. 2007. Inflammatory bowel disease: is it really just another break in the wall? Gut. 56(1):6–8. doi: 10.1136/gut.2006.104182.
  • Wong CM, Tsang FH, Ng IO. 2018. Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications. Nat Rev Gastroenterol Hepatol. 15(3):137–151. doi: 10.1038/nrgastro.2017.169.
  • Wong SH, Kwong TNY, Chow TC, Luk AKC, Dai RZW, Nakatsu G, Lam TYT, Zhang L, Wu JCY, Chan FKL, et al. 2017. Quantitation of faecal Fusobacterium improves faecal ­immunochemical test in detecting advanced colorectal neoplasia. Gut. 66(8):1441–1448. doi: 10.1136/gutjnl-2016-312766.
  • Wu F, Zhang S, Dassopoulos T, Harris ML, Bayless TM, Meltzer SJ, Brant SR, Kwon JH. 2010. Identification of microRNAs associated with ileal and colonic Crohn’s disease. Inflamm Bowel Dis. 16(10):1729–1738. doi: 10.1002/ibd.21267.
  • Xiao YT, Yan WH, Cao Y, Yan JK, Cai W. 2016. Neutralization of IL-6 and TNF-α ameliorates intestinal permeability in DSS-induced colitis. Cytokine. 83:189–192. doi: 10.1016/j.cyto.2016.04.012.
  • Xie YF, Shu R, Jiang SY, Liu DL, Zhang XL. 2011. Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues. Int J Oral Sci. 3(3):125–134. doi: 10.4248/IJOS11046.
  • Yamaguchi Y, Kurita-Ochiai T, Kobayashi R, Suzuki T, Ando T. 2015. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis. Pathog Dis. 73(4):ftv011. doi: 10.1093/femspd/ftv011.
  • Yamamura K, Baba Y, Nakagawa S, Mima K, Miyake K, Nakamura K, Sawayama H, Kinoshita K, Ishimoto T, Iwatsuki M, et al. 2016. Human microbiome fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res. 22(22):5574–5581. doi: 10.1158/1078-0432.CCR-16-1786.
  • Yamaoka Y, Suehiro Y, Hashimoto S, Hoshida T, Fujimoto M, Watanabe M, Imanaga D, Sakai K, Matsumoto T, Nishioka M, et al. 2018. Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J Gastroenterol. 53(4):517–524. doi: 10.1007/s00535-017-1382-6.
  • Yan H, Zhang X, Xu Y. 2020. Aberrant expression of miR-21 in patients with inflammatory bowel disease: A protocol for systematic review and meta analysis. Medicine (Baltimore). 99(17):e19693.). doi: 10.1097/MD.0000000000019693.
  • Yan K, Lin Q, Tang K, Liu S, Du Y, Yu X, Li S. 2020. Substance P participates in periodontitis by upregulating HIF-1α and RANKL/OPG ratio. BMC Oral Health. 20(1):27. doi: 10.1186/s12903-020-1017-9.
  • Yang Y, Ma Y, Shi C, Chen H, Zhang H, Chen N, Zhang P, Wang F, Yang J, Yang J, et al. 2013. Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB. Biochem Biophys Res Commun. 434(4):746–752. doi: 10.1016/j.bbrc.2013.03.122.
  • Yang Y, Weng W, Peng J, Hong L, Yang L, Toiyama Y, Gao R, Liu M, Yin M, Pan C, et al. 2017. Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor-κB, and Up-regulating Expression of MicroRNA-21. Gastroenterology. 152(4):851–866.e24. doi: 10.1053/j.gastro.2016.11.018.
  • Yde Aagaard ME, Frahm Kirk K, Linde Nielsen H, Harder Tarpgaard I, Bach Hansen J, Nielsen H. 2020. Campylobacter concisus is prevalent in the gastrointestinal tract of patients with microscopic colitis. Scand J Gastroenterol. 55(8):924–930. doi: 10.1080/00365521.2020.1792976.
  • Yiangou Y, Facer P, Dyer NH, Chan CL, Knowles C, Williams NS, Anand P. 2001. Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet. 357(9265):1338–1339. doi: 10.1016/s0140-6736(00)04503-7.
  • Yilmaz O, Sater AA, Yao L, Koutouzis T, Pettengill M, Ojcius DM. 2010. ATP-dependent activation of an inflammasome in primary gingival epithelial cells infected by Porphyromonas gingivalis. Cell Microbiol. 12(2):188–198. 98. PMID: 11501 doi: 10.1111/j.1462-5822.2009.01390.x.
  • Yin J, Ren Y, Yang K, Wang W, Wang T, Xiao W, Yang H. 2022. The role of hypoxia-inducible factor 1-alpha in inflammatory bowel disease. Cell Biol Int. 46(1):46–51. doi: 10.1002/cbin.11712.
  • Yoneda T, Tomofuji T, Ekuni D, Azuma T, Maruyama T, Fujimori K, Sugiura Y, Morita M. 2019. Serum microRNAs and chronic periodontitis: a case-control study. Arch Oral Biol. 101:57–63. doi: 10.1016/j.archoralbio.2019.03.009.
  • Yoo SH, Jung HS, Sohn WS, Kim BH, Ku BH, Kim YS, Park SW, Hahm KB. 2008. Volatile sulfur compounds as a predictor for esophagogastroduodenal mucosal injury. Gut Liver. 2(2):113–118. doi: 10.5009/gnl.2008.2.2.113.
  • Yuan J, Chen C, Cui J, Lu J, Yan C, Wei X, Zhao X, Li N, Li S, Xue G, et al. 2019. Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae. Cell Metab. 30(4):675–688.e7. Erratum in: cell Metab. 2019 Dec 3;30(6):1172. doi: 10.1016/j.cmet.2019.08.018.
  • Yuan YY, Xie KX, Wang SL, Yuan LW. 2018. Inflammatory caspase-related pyroptosis: mechanism, regulation and therapeutic potential for inflammatory bowel disease. Gastroenterol Rep (Oxf). 6(3):167–176. doi: 10.1093/gastro/goy011.
  • Yun LW, Decarlo AA, Hunter N. 2007. Blockade of protease-activated receptors on T cells correlates with altered proteolysis of CD27 by gingipains of Porphyromonas gingivalis. Clin Exp Immunol. 150(2):217–229. doi: 10.1111/j.1365-2249.2007.03488.x.
  • Zaki A, Fawzy A, Akel SY, Gamal H, Elshimy RAA. 2022. Evaluation of microRNA 92a expression and its target protein bim in colorectal cancer. Asian Pac J Cancer Prev. 23(2):723–730. doi: 10.31557/APJCP.2022.23.2.723.
  • Zaki MH, Lamkanfi M, Kanneganti TD. 2011. The Nlrp3 inflammasome: contributions to intestinal homeostasis. Trends Immunol. 32(4):171–179. doi: 10.1016/j.it.2011.02.002.
  • Zhang C, Xu C, Gao L, Li X, Zhao C. 2021. Porphyromonas gingivalis lipopolysaccharide promotes T-hel per17 cell differentiation by upregulating Delta-like ligand 4 expression on CD14+ monocytes. PeerJ. 9:e11094. doi: 10.7717/peerj.11094.
  • Zhang G, Ghosh S. 2001. Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity. J Clin Invest. 107(1):13–19. doi: 10.1172/JCI11837.
  • Zhang J, Yu C, Zhang X, Chen H, Dong J, Lu W, Song Z, Zhou W. 2018. Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice. J Neuroinflammation. 15(1):37. doi: 10.1186/s12974-017-1052-x.
  • Zhang L, Gao X, Zhou J, Chen S, Zhang J, Zhang Y, Chen B, Yang J. 2020. Increased risks of dental caries and periodontal disease in Chinese patients with inflammatory bowel disease. Int Dent J. 70(3):227–236. doi: 10.1111/idj.12542.
  • Zhang L, Zhang F, He DK, Fan XM, Shen J. 2018. MicroRNA-21 is upregulated during intestinal barrier dysfunction induced by ischemia reperfusion. Kaohsiung J Med Sci. 34(10):556–563. doi: 10.1016/j.kjms.2018.05.006.
  • Zhao P, Liu J, Pan C, Pan Y. 2014. NLRP3 inflammasome is required for apoptosis of Aggregatibacter actinomycetemcomitans-infected human osteoblastic MG63 cells. Acta Histochem. 116(7):1119–1124. doi: 10.1016/j.acthis.2014.05.008.
  • Zheng T, Ma G, Tang M, Li Z, Xu R. 2018. IL-8 Secreted from M2 Macrophages Promoted Prostate Tumorigenesis via STAT3/MALAT1 Pathway. Int J Mol Sci. 20(1):98. doi: 10.3390/ijms20010098.