PEER-REVIEWED STUDIES
The Science Behind OraStripdx
Each reference under a topic contains a link to the cited publicationor abstract. In many of the papers below, thiols are referred to as “VSCs” or “volatile sulfur compounds.”
Thiols are like alcohols but have a sulfur atom -SH instead of an oxygen -OH.
The color change on OraStripdx is directly related to the concentration of thiols in the oral fluid sample.
The concentration of thiols in oral fluid is directly related to periodontal disease activity. The concentration of thiols decreases after periodontal therapy.
Dogs
- Queck KE, Chapman A, Herzog LJ, Shell-Martin T, Burgess-Cassler A, McClure GD. Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination. J Am Anim Hosp Assoc. 2018 May/Jun;54(3):132-137. doi: 10.5326/JAAHA-MS-6607. Epub 2018 Mar 20. PMID: 29558213.
- Manfra Marretta S, Leesman M, Burgess-Cassler A, McClure GD Jr, Buelow M, Finn M. Pilot evaluation of a novel test strip for the assessment of dissolved thiol levels, as an indicator of canine gingival health and periodontal status. Can Vet J. 2012 Dec;53(12):1260-5. PMID: 23729822; PMCID: PMC3500115.
- Culham N, Rawlings JM. Oral malodor and its relevance to periodontal disease in the dog. J Vet Dent. 1998 Dec;15(4):165-8. doi: 10.1177/089875649801500401. PMID: 10518872.
- Rawlings JM, Culham N. Studies of oral malodor in the dog. J Vet Dent. 1998 Dec;15(4):169-73. doi: 10.1177/089875649801500402. PMID: 10518873.
- Simone AJ, Logan EI, Livgren R, Suelzer M. Oral malodor in beagles: association with indicators of periodontal disease. J Clin Dent. 1997;8(6):163-8. PMID: 9586533.
Humans
- Abdullah MA, Alasqah M, Sanaa MS, Gufran K. The Relationship between Volatile Sulfur Compounds and the Severity of Chronic Periodontitis: A Cross-sectional Study. J Pharm Bioallied Sci. 2020 Aug;12(Suppl 1):S268-S273. doi: 10.4103/jpbs.JPBS_81_20. Epub 2020 Aug 28. PMID: 33149469; PMCID: PMC7595518.
- Kushkevych I, Coufalová M, Vítězová M, Rittmann SKR. Sulfate-Reducing Bacteria of the Oral Cavity and Their Relation with Periodontitis-Recent Advances. J Clin Med. 2020 Jul 23;9(8):2347. doi: 10.3390/jcm9082347. PMID: 32717883; PMCID: PMC7464432.
- Iatropoulos A, Panis V, Mela E, Stefaniotis T, Madianos PN, Papaioannou W. Changes of volatile sulphur compounds during therapy of a case series of patients with chronic periodontitis and halitosis. J Clin Periodontol. 2016 Apr;43(4):359-65. doi: 10.1111/jcpe.12521. Epub 2016 Mar 29. PMID: 26824613.
- Takeuchi H, Machigashira M, Yamashita D, Kozono S, Nakajima Y, Miyamoto M, Takeuchi N, Setoguchi T, Noguchi K. The association of periodontal disease with oral malodour in a Japanese population. Oral Dis. 2010 Oct;16(7):702-6. doi: 10.1111/j.1601-0825.2010.01685.x. PMID: 20561223.
- Tsai CC, Chou HH, Wu TL, Yang YH, Ho KY, Wu YM, Ho YP. The levels of volatile sulfur compounds in mouth air from patients with chronic periodontitis. J Periodontal Res. 2008 Apr;43(2):186-93. doi: 10.1111/j.1600-0765.2007.01011.x. PMID: 18302621.
- Vianna ME, Holtgraewe S, Seyfarth I, Conrads G, Horz HP. Quantitative analysis of three hydrogenotrophic microbial groups, methanogenic archaea, sulfate-reducing bacteria, and acetogenic bacteria, within plaque biofilms associated with human periodontal disease. J Bacteriol. 2008 May;190(10):3779-85. doi: 10.1128/JB.01861-07. Epub 2008 Mar 7. PMID: 18326571; PMCID: PMC2394984.
- Zappacosta B, Manni A, Persichilli S, Boari A, Scribano D, Minucci A, Raffaelli L, Giardina B, De Sole P. Salivary thiols and enzyme markers of cell damage in periodontal disease. Clin Biochem. 2007 Jun;40(9-10):661-5. doi: 10.1016/j.clinbiochem.2007.01.011. Epub 2007 Jan 26. PMID: 17328883.
- Gleissner C, Springborn I, Willershausen B. Effect of periodontal therapy on sulcular sulphide level a longitudinal study. Eur J Med Res. 2003 Jan 28;8(1):33-46. PMID: 12578752.
- Gleissner C, Springborn I, Willershausen B. Evaluation of sulcular sulphide level monitoring using a portable sensor system. Eur J Med Res. 2002 Nov 25;7(11):491-501. PMID: 12568978.
- Morita M, Wang HL. Effect of initial periodontal therapy on sulcular/tongue sulfide level. A pilot study. J Clin Periodontol. 2002 Sep;29(9):844-7. doi: 10.1034/j.1600-051x.2002.290909.x. PMID: 12423298.
- Langendijk PS, Hanssen JT, Van der Hoeven JS. Sulfate-reducing bacteria in association with human periodontitis. J Clin Periodontol. 2000 Dec;27(12):943-50. doi: 10.1034/j.1600-051x.2000.027012943.x. PMID: 11140562.
As a gingival sulcus deepens and becomes a periodontal pocket, it becomes more anaerobic, providing a favorable environment for the flourishing of periodontal pathogens.
- Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, Gamonal J, Diaz PI. The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J. 2013 May;7(5):1016-25. doi: 10.1038/ismej.2012.174. Epub 2013 Jan 10. PMID: 23303375; PMCID: PMC3635234.
- Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev. 2001 Oct;14(4):727-52, table of contents. doi: 10.1128/CMR.14.4.727-752.2001. PMID: 11585783; PMCID: PMC89001.
- Loesche WJ, Gusberti F, Mettraux G, Higgins T, Syed S. Relationship between oxygen tension and subgingival bacterial flora in untreated human periodontal pockets. Infect Immun. 1983 Nov;42(2):659-67. doi: 10.1128/iai.42.2.659-667.1983. PMID: 6642647; PMCID: PMC264480.
The most prominent periodontal pathogens are anaerobes that produce thiols.
Pophyromonas species
- Iwashita N, Nomura R, Shirai M, Kato Y, Murakami M, Matayoshi S, Kadota T, Shirahata S, Ohzeki L, Arai N, Yasuda J, Yasuda H, Inaba H, Matsumoto-Nakano M, Nakano K, Asai F. Identification and molecular characterization of Porphyromonas gulae fimA types among cat isolates. Vet Microbiol. 2019 Feb;229:100-109. doi: 10.1016/j.vetmic.2018.12.018. Epub 2018 Dec 19. PMID: 30642584.
- Nakamura S, Shioya K, Hiraoka BY, Suzuki N, Hoshino T, Fujiwara T, Yoshinari N, Ansai T, Yoshida A. Porphyromonas gingivalis hydrogen sulfide enhances methyl mercaptan-induced pathogenicity in mouse abscess formation. Microbiology (Reading). 2018 Apr;164(4):529-539. doi: 10.1099/mic.0.000640. Epub 2018 Feb 28. PMID: 29488863.
- Stephen AS, Millhouse E, Sherry L, Aduse-Opoku J, Culshaw S, Ramage G, Bradshaw DJ, Burnett GR, Allaker RP. In Vitro Effect of Porphyromonas gingivalis Methionine Gamma Lyase on Biofilm Composition and Oral Inflammatory Response. PLoS One. 2016 Dec 29;11(12):e0169157. doi: 10.1371/journal.pone.0169157. PMID: 28033374; PMCID: PMC5199072.
- Chi XP, Ouyang XY, Wang YX. Hydrogen sulfide synergistically upregulates Porphyromonas gingivalis lipopolysaccharide-induced expression of IL-6 and IL-8 via NF-κB signalling in periodontal fibroblasts. Arch Oral Biol. 2014 Sep;59(9):954-61. doi: 10.1016/j.archoralbio.2014.05.022. Epub 2014 Jun 2. PMID: 24927331.
- Yamasaki Y, Nomura R, Nakano K, Naka S, Matsumoto-Nakano M, Asai F, Ooshima T. Distribution of periodontopathic bacterial species in dogs and their owners. Arch Oral Biol. 2012 Sep;57(9):1183-8. doi: 10.1016/j.archoralbio.2012.02.015. Epub 2012 Mar 13. PMID: 22417880.
- Dahlén G, Charalampakis G, Abrahamsson I, Bengtsson L, Falsen E. Predominant bacterial species in subgingival plaque in dogs. J Periodontal Res. 2012 Jun;47(3):354-64. doi: 10.1111/j.1600-0765.2011.01440.x. Epub 2011 Dec 19. PMID: 22181039.
- Kato Y, Shirai M, Murakami M, Mizusawa T, Hagimoto A, Wada K, Nomura R, Nakano K, Ooshima T, Asai F. Molecular detection of human periodontal pathogens in oral swab specimens from dogs in Japan. J Vet Dent. 2011 Summer;28(2):84-9. doi: 10.1177/089875641102800204. PMID: 21916371.
- Yoshimura M, Nakano Y, Yamashita Y, Oho T, Saito T, Koga T. Formation of methyl mercaptan from L-methionine by Porphyromonas gingivalis. Infect Immun. 2000 Dec;68(12):6912-6. doi: 10.1128/IAI.68.12.6912-6916.2000. PMID: 11083813; PMCID: PMC97798.
- Norris JM, Love DN. The association of two recombinant proteinases of a feline strain of Porphyromonas gingivalis with periodontal disease in cats. Vet Microbiol. 2000 Jan;71(1-2):69-80. doi: 10.1016/s0378-1135(99)00154-6. PMID: 10665535.
- DeCarlo AA Jr, Windsor LJ, Bodden MK, Harber GJ, Birkedal-Hansen B, Birkedal-Hansen H. Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. J Dent Res. 1997 Jun;76(6):1260-70. doi: 10.1177/00220345970760060501. PMID: 9168859.
- Madianos PN, Papapanou PN, Socransky SS, Dahlen G, Sandros J. Host-related genotypic heterogeneity of Porphyromonas gingivalis strains in the beagle dog. Oral Microbiol Immunol. 1994 Aug;9(4):241-7. doi: 10.1111/j.1399-302x.1994.tb00065.x. PMID: 7478765.
Treponema species
- Kwon D, Bae K, Kim H, Kim SH, Lee D, Lee JH. Treponema denticola as a prognostic biomarker for periodontitis in dogs. PLoS One. 2022 Jan 21;17(1):e0262859. doi: 10.1371/journal.pone.0262859. PMID: 35061858; PMCID: PMC8782364.
- Chu L, Wu Y, Xu X, Phillips L, Kolodrubetz D. Glutathione catabolism by Treponema denticola impacts its pathogenic potential. Anaerobe. 2020 Apr;62:102170. doi: 10.1016/j.anaerobe.2020.102170. Epub 2020 Feb 7. PMID: 32044394; PMCID: PMC7153967.
- Zhang JH, Dong Z, Chu L. Hydrogen sulfide induces apoptosis in human periodontium cells. J Periodontal Res. 2010 Feb;45(1):71-8. doi: 10.1111/j.1600-0765.2009.01202.x. Epub 2009 Jul 8. PMID: 19602114.
- Chu L, Lai Y, Xu X, Eddy S, Yang S, Song L, Kolodrubetz D. A 52-kDa leucyl aminopeptidase from treponema denticola is a cysteinylglycinase that mediates the second step of glutathione metabolism. J Biol Chem. 2008 Jul 11;283(28):19351-8. doi: 10.1074/jbc.M801034200. Epub 2008 May 15. PMID: 18482986; PMCID: PMC2443665.
- Nordhoff M, Rühe B, Kellermeier C, Moter A, Schmitz R, Brunnberg L, Wieler LH. Association of Treponema spp. with canine periodontitis. Vet Microbiol. 2008 Mar 18;127(3-4):334-42. doi: 10.1016/j.vetmic.2007.09.011. Epub 2007 Sep 29. PMID: 17997236.
- Fukamachi H, Nakano Y, Okano S, Shibata Y, Abiko Y, Yamashita Y. High production of methyl mercaptan by L-methionine-alpha-deamino-gamma-mercaptomethane lyase from Treponema denticola. Biochem Biophys Res Commun. 2005 May 27;331(1):127-31. doi: 10.1016/j.bbrc.2005.03.139. PMID: 15845368.
- Chu L, Ebersole JL, Kurzban GP, Holt SC. Cystalysin, a 46-kilodalton cysteine desulfhydrase from Treponema denticola, with hemolytic and hemoxidative activities. Infect Immun. 1997 Aug;65(8):3231-8. doi: 10.1128/iai.65.8.3231-3238.1997. PMID: 9234780; PMCID: PMC175457.
- Riviere GR, Thompson AJ, Brannan RD, McCoy DE, Simonson LG. Detection of pathogen-related oral spirochetes, Treponema denticola, and Treponema socranskii in dental plaque from dogs. J Vet Dent. 1996 Dec;13(4):135-8. PMID: 9520788.
- Haapasalo M, Singh U, McBride BC, Uitto VJ. Sulfhydryl-dependent attachment of Treponema denticola to laminin and other proteins. Infect Immun. 1991 Nov;59(11):4230-7. doi: 10.1128/iai.59.11.4230-4237.1991. PMID: 1937780; PMCID: PMC259021.
Thiols destroy gingival tissue, compromising epithelial barrier function and promoting inflammation. Thiols degrade the periodontal ligament and induce resorption and loss of alveolar bone.
- Ni K, Hua Y. Hydrogen sulfide exacerbated periodontal inflammation and induced autophagy in experimental periodontitis. Int Immunopharmacol. 2021 Apr;93:107399. doi: 10.1016/j.intimp.2021.107399. Epub 2021 Jan 30. PMID: 33529908.
- Stephen AS, Millhouse E, Sherry L, Aduse-Opoku J, Culshaw S, Ramage G, Bradshaw DJ, Burnett GR, Allaker RP. In Vitro Effect of Porphyromonas gingivalis Methionine Gamma Lyase on Biofilm Composition and Oral Inflammatory Response. PLoS One. 2016 Dec 29;11(12):e0169157. doi: 10.1371/journal.pone.0169157. PMID: 28033374; PMCID: PMC5199072.
- Irie K, Ekuni D, Tomofuji T, Endo Y, Kasuyama K, Yaegaki K, Morita M. Combined effects of hydrogen sulfide and lipopolysaccharide on osteoclast differentiation in rats. J Periodontol. 2012 Apr;83(4):522-7. doi: 10.1902/jop.2011.110315. Epub 2011 Sep 12. PMID: 21910595.
- Chen W, Kajiya M, Giro G, Ouhara K, Mackler HE, Mawardi H, Boisvert H, Duncan MJ, Sato K, Kawai T. Bacteria-derived hydrogen sulfide promotes IL-8 production from epithelial cells. Biochem Biophys Res Commun. 2010 Jan 1;391(1):645-50. doi: 10.1016/j.bbrc.2009.11.113. Epub 2009 Nov 22. PMID: 19932683; PMCID: PMC2874960.
- Irie K, Ekuni D, Yamamoto T, Morita M, Yaegaki K, Ii H, Imai T. A single application of hydrogen sulphide induces a transient osteoclast differentiation with RANKL expression in the rat model. Arch Oral Biol. 2009 Aug;54(8):723-9. doi: 10.1016/j.archoralbio.2009.05.006. Epub 2009 Jun 12. PMID: 19524214.
- Johnson PW, Lancero H. Function of gingival fibroblasts and periodontal ligament cells in the presence of methyl mercaptan. Quintessence Int. 1999 May;30(5):343-9. PMID: 10635290.
- DeCarlo AA, Grenett HE, Harber GJ, Windsor LJ, Bodden MK, Birkedal-Hansen B, Birkedal-Hansen H. Induction of matrix metalloproteinases and a collagen-degrading phenotype in fibroblasts and epithelial cells by secreted Porphyromonas gingivalis proteinase. J Periodontal Res. 1998 Oct;33(7):408-20. doi: 10.1111/j.1600-0765.1998.tb02337.x. PMID: 9842506.
- Abe N, Kadowaki T, Okamoto K, Nakayama K, Ohishi M, Yamamoto K. Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease. J Biochem. 1998 Feb;123(2):305-12. doi: 10.1093/oxfordjournals.jbchem.a021937. PMID: 9538207.
- Johnson P, Yaegaki K, Tonzetich J. Effect of methyl mercaptan on synthesis and degradation of collagen. J Periodontal Res. 1996 Jul;31(5):323-9. doi: 10.1111/j.1600-0765.1996.tb00499.x. PMID: 8858536.
- Lancero H, Niu J, Johnson PW. Exposure of periodontal ligament cells to methyl mercaptan reduces intracellular pH and inhibits cell migration. J Dent Res. 1996 Dec;75(12):1994-2002. doi: 10.1177/00220345960750121201. PMID: 9033455.
- Ratkay LG, Waterfield JD, Tonzetich J. Stimulation of enzyme and cytokine production by methyl mercaptan in human gingival fibroblast and monocyte cell cultures. Arch Oral Biol. 1995 Apr;40(4):337-44. doi: 10.1016/0003-9969(94)00165-8. PMID: 7605261.
- Kadowaki T, Yoneda M, Okamoto K, Maeda K, Yamamoto K. Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis. J Biol Chem. 1994 Aug 19;269(33):21371-8. PMID: 8063764.
- Johnson PW, Yaegaki K, Tonzetich J. Effect of volatile thiol compounds on protein metabolism by human gingival fibroblasts. J Periodontal Res. 1992 Nov;27(6):553-61. doi: 10.1111/j.1600-0765.1992.tb01736.x. PMID: 1460544.
- Johnson PW, Ng W, Tonzetich J. Modulation of human gingival fibroblast cell metabolism by methyl mercaptan. J Periodontal Res. 1992 Sep;27(5):476-83. doi: 10.1111/j.1600-0765.1992.tb01820.x. PMID: 1403576.
- Ng W, Tonzetich J. Effect of hydrogen sulfide and methyl mercaptan on the permeability of oral mucosa. J Dent Res. 1984 Jul;63(7):994-7. doi: 10.1177/00220345840630071701. PMID: 6588090.
Periodontal disease is strongly linked to systemic diseases.
Multiple systemic diseases
- Harvey C. The Relationship Between Periodontal Infection and Systemic and Distant Organ Disease in Dogs. Vet Clin North Am Small Anim Pract. 2022 Jan;52(1):121-137. doi: 10.1016/j.cvsm.2021.09.004. PMID: 34838247.
- Pereira Dos Santos JD, Cunha E, Nunes T, Tavares L, Oliveira M. Relation between periodontal disease and systemic diseases in dogs. Res Vet Sci. 2019 Aug;125:136-140. doi: 10.1016/j.rvsc.2019.06.007. Epub 2019 Jun 12. PMID: 31226571.
- Penlington L, Faixová Z.Periodontal Disease in Association with Systemic Diseases in the Dog. Folia Veterinaria 2019;63(4):1-8. https://doi.org/10.2478/fv-2019-0031.
- Pavlica Z, Petelin M, Juntes P, Erzen D, Crossley DA, Skaleric U. Periodontal disease burden and pathological changes in organs of dogs. J Vet Dent. 2008 Jun;25(2):97-105. doi: 10.1177/089875640802500210. PMID: 18751659.
- Niemiec BA. Periodontal disease. Top Companion Anim Med. 2008 May;23(2):72-80. doi: 10.1053/j.tcam.2008.02.003. PMID: 18482707.
- Chambers DA, Crawford JM, Mukherjee S, Cohen RL. Aspartate aminotransferase increases in crevicular fluid during experimental periodontitis in beagle dogs. J Periodontol. 1984 Sep;55(9):526-30. doi: 10.1902/jop.1984.55.9.526. PMID: 6384467.
Inflammatory markers/indices
- Tamura K, Tokuzen-Tai M, Siddiqui YD, Tamura-Naito H, Nagahara Y, Hatanaka-Takeuchi K, Yamamoto T, Takashiba S. Estimation of periodontal pocket surface area in small to medium dogs: a proof-of-concept study. BMC Vet Res. 2022 Jan 3;18(1):13. doi: 10.1186/s12917-021-03116-0. PMID: 34980120; PMCID: PMC8722143.
- Rawlinson JE, Goldstein RE, Reiter AM, Attwater DZ, Harvey CE. Association of periodontal disease with systemic health indices in dogs and the systemic response to treatment of periodontal disease. J Am Vet Med Assoc. 2011 Mar 1;238(5):601-9. doi: 10.2460/javma.238.5.601. PMID: 21355802.
Even Stage 1 periodontal disease (gingivitis, no bone loss) is associated with systemic disease markers.
Periodontal disease is not reliably detected through an awake visual examination alone. Only through a comprehensive oral health assessment can periodontal disease be properly diagnosed, staged and treated. Only through proper treatment and at-home care can periodontal disease be slowed.
- Bellows J, Berg ML, Dennis S, Harvey R, Lobprise HB, Snyder CJ, Stone AES, Van de Wetering AG. 2019 AAHA Dental Care Guidelines for Dogs and Cats. J Am Anim Hosp Assoc. 2019 Mar/Apr;55(2):49-69. doi: 10.5326/JAAHA-MS-6933. PMID: 30776257.
- Niemiec B, Gawor J, Nemec A, Clarke D, McLeod K, Tutt C, Gioso M, Steagall PV, Chandler M, Morgenegg G, Jouppi R. World Small Animal Veterinary Association Global Dental Guidelines. J Small Anim Pract. 2020 Jul;61(7):E36-E161. doi: 10.1111/jsap.13132.
