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Free amino acid composition of saliva in patients with healthy periodontium and periodontitis

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Abstract

Objectives

To identify and compare the free amino acids in the saliva of periodontitis patients and healthy individuals and to assess their levels in different periodontal disease types.

Materials and methods

There were three groups: healthy individuals (control (C); n = 20), Stage III Grade B generalized periodontitis (GP-B; n = 20), and Stage III Grade C generalized periodontitis (GP-C; n = 20). Clinical periodontal parameters were measured. Amino acid analysis of the saliva was accomplished by liquid chromatography–mass spectrometry (LC MS/MS), taking the mean concentration.

Results

Citrulline and carnosine concentrations were significantly higher in patients with periodontitis than in the control group (p < 0.017). Methionine, glutamic acid, and arginine showed significantly higher concentrations in GP-C, whereas proline and tryptophan showed higher concentrations in the GP-B group (p < 0.017). There was a significant correlation between methionine, citrulline, arginine, and carnosine and clinical periodontal parameters.

Conclusions

Our results demonstrate that periodontal status and disease type can result in variations in salivary amino acid (AA) content in correlation with clinical inflammatory signs. The significant correlation of methionine, citrulline, carnosine, and arginine with clinical parameters, regardless of systemic status, suggests that the levels of different salivary free AAs play roles in periodontitis.

Clinical relevance

Salivary free AAs may be suggested as a potential diagnostic compound in patients with periodontitis.

Clinical trial registration

ClinicalTrials.gov NCT04642716

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References

  1. Kurgan Ş, Önder C, Balcı N, Fentoğlu Ö, Eser F, Balseven M, Serdar MA, Tatakis DN, Günhan M (2017) Gingival crevicular fluid tissue/blood vessel-type plasminogen activator and plasminogen activator inhibitor-2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy. J Periodontal Res 52:574–581. https://doi.org/10.1111/jre.12425

    Article  PubMed  Google Scholar 

  2. Hajishengallis G (2014) Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol 35:3–11. https://doi.org/10.1016/j.it.2013.09.001

    Article  PubMed  Google Scholar 

  3. Reddy MK (2020) Amino acid. https://www.britannica.com/science/amino-acid. Accessed 16 January 2021

  4. Bin P, Liu S, Chen S, Zeng Z, Huang R, Yin Y, Liu G (2017) The effect of aspartate supplementation on the microbial composition and innate immunity on mice. Amino Acids 49:2045–2051. https://doi.org/10.1007/s00726-017-2467-5

    Article  PubMed  Google Scholar 

  5. Li JH, Yu JP, Yu HG, Xu XM, Yu LL, Liu J, Luo HS (2005) Melatonin reduces inflammatory injury through inhibiting NF-kappaB activation in rats with colitis. Mediat Inflamm 2005:185–193. https://doi.org/10.1155/mi.2005.185

    Article  Google Scholar 

  6. Wang W, Wu Z, Lin G, Hu S, Wang B, Dai Z, Wu G (2014) Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells. J Nutr 144:1540–1548. https://doi.org/10.3945/jn.114.194001

    Article  PubMed  Google Scholar 

  7. Li P, Yin YL, Li D, Kim SW, Wu G (2007) Amino acids and immune function. Br J Nutr 98:237–252. https://doi.org/10.1017/s000711450769936x

    Article  PubMed  Google Scholar 

  8. Cruzat VF, Krause M, Newsholme P (2014) Amino acid supplementation and impact on immune function in the context of exercise. J Int Soc Sports Nutr 11:61. https://doi.org/10.1186/s12970-014-0061-8

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lanz TV, Becker S, Mohapatra SR, Opitz CA, Wick W, Platten M (2017) Suppression of Th1 differentiation by tryptophan supplementation in vivo. Amino Acids 49:1169–1175. https://doi.org/10.1007/s00726-017-2415-4

    Article  PubMed  Google Scholar 

  10. Song Z, Tong G, Xiao K, Le FJ, Ke Y, Hu C (2016) L-cysteine protects intestinal integrity, attenuates intestinal inflammation and oxidant stress, and modulates NF-κB and Nrf2 pathways in weaned piglets after LPS challenge. Innate Immunol 22:152–161. https://doi.org/10.1177/1753425916632303

    Article  Google Scholar 

  11. Kretzmann NA, Fillmann H, Mauriz JL, Marroni CA, Marroni N, González-Gallego J, Tuñón MJ (2008) Effects of glutamine on proinflammatory gene expression and activation of nuclear factor kappa B and signal transducers and activators of transcription in TNBS-induced colitis. Inflamm Bowel Dis 14:1504–1513. https://doi.org/10.1002/ibd.20543

    Article  PubMed  Google Scholar 

  12. Robles HV, Ochoa KFC, Nava P, Olivares AS, Shibayama M, Schnoor M (2017) Analyzing beneficial effects of nutritional supplements on intestinal epithelial barrier functions during experimental colitis. J Vis Exp:e55095. https://doi.org/10.3791/55095

  13. Sido B, Seel C, Hochlehnert A, Breitkreutz R, Dröge W (2006) Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation? Dig Dis Sci 51:2170–2179. https://doi.org/10.1007/s10620-006-9473-x

    Article  PubMed  Google Scholar 

  14. Önder C, Kurgan Ş, Altıngöz SM, Bağış N, Uyanık M, Serdar MA, Kantarcı A, Günhan M (2017) Impact of non-surgical periodontal therapy on saliva and serum levels of markers of oxidative stress. Clin Oral Investig 21:1961–1969. https://doi.org/10.1007/s00784-016-1984-z

    Article  PubMed  Google Scholar 

  15. Dede F, Ozden FO, Avcı B (2013) 8-hydroxy-deoxyguanosine levels in gingival crevicular fluid and saliva in patients with chronic periodontitis after initial periodontal treatment. J Periodontol 84:821–828. https://doi.org/10.1902/jop.2012.120195

    Article  PubMed  Google Scholar 

  16. Breuillard C, Bonhomme S, Couderc R, Cynober L, De Bandt JP (2015) In vitro anti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats. Br J Nutr 113:120–124. https://doi.org/10.1017/s0007114514002086

    Article  PubMed  Google Scholar 

  17. Blanc MC, Moinard C, Béziel A, Darquy S, Cynober L, De Bandt JP (2005) Arginine and glutamine availability and macrophage functions in the obese insulin-resistant Zucker rat. J Cell Physiol 202:153–159. https://doi.org/10.1002/jcp.20092

    Article  PubMed  Google Scholar 

  18. Graves DT, Cochran D (2003) The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 74:391–401. https://doi.org/10.1902/jop.2003.74.3.391

    Article  PubMed  Google Scholar 

  19. Rajda C, Tajti J, Komoróczy R, Seres E, Klivényi P, Vécsei L (1999) Amino acids in the saliva of patients with migraine. Headache 39:644–649. https://doi.org/10.1046/j.1526-4610.1999.3909644.x

    Article  PubMed  Google Scholar 

  20. Liappis N, Pohl B, Weber HP, El-Karkani H (1986) Free amino acids in the saliva of children with phenylketonuria. Klin Padiatr 198:25–28. https://doi.org/10.1055/s-2008-1026847

    Article  PubMed  Google Scholar 

  21. Cheng F, Wang Z, Huang Y, Duan Y, Wang X (2015) Investigation of salivary free amino acid profile for early diagnosis of breast cancer with ultra performance liquid chromatography-mass spectrometry. Clin Chim Acta 447:23–31. https://doi.org/10.1016/j.cca.2015.05.008

    Article  PubMed  Google Scholar 

  22. Shi M, Sui YT, Peskind ER et al (2011) Salivary tau species are potential biomarkers of Alzheimer's disease. J Alzheimers Dis 27:299–305. https://doi.org/10.3233/jad-2011-110731

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chen Y, Cheng S, Zhang A et al (2018) Salivary analysis based on surface enhanced Raman scattering sensors distinguishes early and advanced gastric cancer patients from healthy persons. J Biomed Nanotechnol 14:1773–1784. https://doi.org/10.1166/jbn.2018.2621

    Article  PubMed  Google Scholar 

  24. Syrjänen SM, Piironen P, Markkanen H (1984) Free amino-acid composition of wax-stimulated whole saliva in human subjects with healthy periodontium, severe chronic periodontitis and post-juvenile periodontitis. Arch Oral Biol 29:735–738. https://doi.org/10.1016/0003-9969(84)90181-x

    Article  PubMed  Google Scholar 

  25. Syrjänen SM, Piironen P, Markkanen H (1987) Free amino-acid content of wax-stimulated human whole saliva as related to periodontal disease. Arch Oral Biol 32:607–610. https://doi.org/10.1016/0003-9969(87)90032-x

    Article  PubMed  Google Scholar 

  26. Syrjänen SM, Alakuijala L, Alakuijala P, Markkanen SO, Markkanen H (1990) Free amino acid levels in oral fluids of normal subjects and patients with periodontal disease. Arch Oral Biol 35:189–193. https://doi.org/10.1016/0003-9969(90)90054-e

    Article  PubMed  Google Scholar 

  27. Tonetti MS, Greenwell H, Kornman KS (2018) Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol 89(Suppl 1):S159–S172. https://doi.org/10.1002/jper.18-0006

    Article  PubMed  Google Scholar 

  28. Cağlayan F, Miloglu O, Altun O, Erel O, Yilmaz AB (2008) Oxidative stress and myeloperoxidase levels in saliva of patients with recurrent aphthous stomatitis. Oral Dis 14:700–704. https://doi.org/10.1111/j.1601-0825.2008.01466.x

    Article  PubMed  Google Scholar 

  29. Le A, Ng A, Kwan T, Cusmano-Ozog K, Cowan TM (2014) A rapid, sensitive method for quantitative analysis of underivatized amino acids by liquid chromatography-tandem mass spectrometry (LC-MS/MS). J Chromatogr B Anal Technol Biomed Life Sci 944:166–174. https://doi.org/10.1016/j.jchromb.2013.11.017

    Article  Google Scholar 

  30. He F, Wu C, Li P, Li N, Zhang D, Zhu Q, Ren W, Peng Y (2018) Functions and signaling pathways of amino acids in intestinal inflammation. Biomed Res Int 2018:9171905. https://doi.org/10.1155/2018/9171905

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ryu OH, Atkinson JC, Hoehn GT, Illei GG, Hart TC (2006) Identification of parotid salivary biomarkers in Sjogren's syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis. Rheumatology (Oxford) 45:1077–1086. https://doi.org/10.1093/rheumatology/kei212

    Article  Google Scholar 

  32. Rad HM, Rabiei M, Sobhani A, Khanjani MS, Taramsar MR, Leili EK (2014) Free amino acids in stimulated and unstimulated whole saliva: advantages or disadvantages. J Oral Rehabil 41:759–767. https://doi.org/10.1111/joor.12197

    Article  Google Scholar 

  33. Battistone GC, Burnett GW (1961) The free amino acid composition of human saliva. Arch Oral Biol 3:161–170. https://doi.org/10.1016/0003-9969(61)90133-9

    Article  PubMed  Google Scholar 

  34. Kirch ER, Kesel RG, O'Donnell JF, Wach EC (1947) Amino acids in human saliva. J Dent Res 26:297–301. https://doi.org/10.1177/00220345470260040401

    Article  PubMed  Google Scholar 

  35. Menaka KB, Ramesh A, Thomas B, Kumari NS (2009) Estimation of nitric oxide as an inflammatory marker in periodontitis. J Indian Soc Periodontol 13(2):75–78. https://doi.org/10.4103/0972-124X.55842

    Article  PubMed  PubMed Central  Google Scholar 

  36. Papadia C, Osowska S, Cynober L, Forbes A (2018) Citrulline in health and disease. Review on human studies. Clin Nutr 37(6 Pt A):1823–1828. https://doi.org/10.1016/j.clnu.2017.10.009

    Article  PubMed  Google Scholar 

  37. Kaore NS, Kaore MN (2014) Citrulline: pharmacological perspectives and role as a biomarker in diseases and toxicities. In: Gupta RC (ed) Biomarkers in toxicology. Academic Press, pp 883–905

  38. Wang Y, Huang X, He F (2019) Mechanism and role of nitric oxide signaling in periodontitis. Exp Ther Med 18(5):3929–3935. https://doi.org/10.3892/etm.2019.8044

    Article  PubMed  PubMed Central  Google Scholar 

  39. Schröcksnadel K, Wirleitner B, Winkler C, Fuchs D (2006) Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta 364:82–90. https://doi.org/10.1016/j.cca.2005.06.013

    Article  PubMed  Google Scholar 

  40. Phang JM, Liu W, Hancock CN, Fischer JW (2015) Proline metabolism and cancer: emerging links to glutamine and collagen. Curr Opin Clin Nutr Metab Care 18:71–77. https://doi.org/10.1097/mco.0000000000000121

    Article  PubMed  Google Scholar 

  41. Patil S, Rao RS, Amrutha N, Sanketh DS (2013) Oral microbial flora in health. World J Dent 4(4):262–266. https://doi.org/10.5005/jp-journals-10015-1242

    Article  Google Scholar 

  42. Metges CC (2000) Contribution of microbial amino acids to amino acid homeostasis of the host. J Nutr 130:1857S–1864S. https://doi.org/10.1093/jn/130.7.1857S

    Article  PubMed  Google Scholar 

  43. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C et al (2011) Metabolite profiles and the risk of developing diabetes. Nat Med 17:448–453. https://doi.org/10.1038/nm.2307

    Article  PubMed  PubMed Central  Google Scholar 

  44. Neis EP, Dejong CH, Rensen SS (2015) The role of microbial amino acid metabolism in host metabolism. Nutrients 7(4):2930–2946. https://doi.org/10.3390/nu7042930

    Article  PubMed  PubMed Central  Google Scholar 

  45. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE et al (2009) Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 106:2365–2370. https://doi.org/10.1038/nm.2307

    Article  PubMed  PubMed Central  Google Scholar 

  46. Crenn P, Neveux N, Chevret S, Jaffray P, Cynober L, Melchior JC, Annane D (2014) Plasma L-citrulline concentrations and its relationship with inflammation at the onset of septic shock: a pilot study. J Crit Care 29:315.e311–315.e316. https://doi.org/10.1016/j.jcrc.2013.11.015

    Article  Google Scholar 

  47. Miyagi Y, Higashiyama M, Gochi A et al (2011) Plasma free amino acid profiling of five types of cancer patients and its application for early detection. PLoS One 6:e24143. https://doi.org/10.1371/journal.pone.0024143

    Article  PubMed  PubMed Central  Google Scholar 

  48. Keskin M, Lähteenmäki H, Rathnayake N, Räisänen IT, Tervahartiala T, Pärnänen P, Şenışık AM et al (2020) Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study. Expert Rev Proteomics 17(10):777–784. https://doi.org/10.1080/14789450.2020.1858056

    Article  PubMed  Google Scholar 

  49. Sorsa T, Bacigalupo J, Könönen M, Pärnänen P, Räisänen IT (2020) Host-modulation therapy and chair-side diagnostics in the treatment of peri-implantitis. Biosensors (Basel) 10(5):44. https://doi.org/10.3390/bios10050044

    Article  Google Scholar 

  50. Grigoriadis A, Räisänen IT, Pärnänen P, Tervahartiala T, Sorsa T, Sakellari D (2021) Prediabetes/ diabetes screening strategy at the periodontal clinic. Clin Exp Dent Res 7:85–92. https://doi.org/10.1002/cre2.338

    Article  PubMed  Google Scholar 

  51. Sorsa T, Alassiri S, Grigoriadis A, Räisänen IT, Pärnänen P, Nwhator SO, Gieselmann DR, Sakellari D (2020) Active MMP-8 (aMMP-8) as a grading and staging biomarker in the periodontitis classification. Diagnostics (Basel) 10(2):61. https://doi.org/10.3390/diagnostics10020061

    Article  Google Scholar 

  52. Lähteenmäki H, Umeizudike KA, Heikkinen AM, Räisänen IT, Rathnayake N, Johannsen G, Tervahartiala T et al (2020) aMMP-8 point-of-care/chairside oral fluid technology as a rapid, non-invasive tool for periodontitis and peri-implantitis screening in a medical care setting. Diagnostics (Basel) 10(8):562. https://doi.org/10.3390/diagnostics10080562

    Article  Google Scholar 

  53. Golub LM, Räisänen IT, Sorsa T, Preshaw PM (2020) An unexplored pharmacologic/diagnostic strategy for peri-implantitis: a protocol proposal. Diagnostics 10(12):1050. https://doi.org/10.3390/diagnostics10121050

    Article  PubMed Central  Google Scholar 

  54. Naluai ÅT, Saadat Vafa L, Gudjonsdottir AH, Arnell H, Browaldh L, Nilsson S, Agardh D (2018) Altered peripheral amino acid profile indicate a systemic impact of active celiac disease and a possible role of amino acids in disease pathogenesis. PLoS One 13:e0193764. https://doi.org/10.1371/journal.pone.0193764

    Article  Google Scholar 

  55. Hull MA, Jones BA, Zurakowski D, Raphael B, Lo C, Jaksic T, Duggan C (2011) Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure. JPEN J Parenter Enteral Nutr 35:181–187. https://doi.org/10.1177/0148607110381406

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Periodontology, Faculty of Dentistry, Istanbul Medipol University, Istanbul, Turkey

    Nur Balci

  2. Department of Periodontology, Faculty of Dentistry, Ankara University, Ankara, Turkey

    Şivge Kurgan

  3. Department of Periodontology, Faculty of Dentistry, Istanbul University, Istanbul, Turkey

    Ali Çekici & Tülin Çakır

  4. Department of Medical Biochemistry, School of Medicine, Acıbadem University, Ankara, Turkey

    Muhittin A. Serdar

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Contributions

NB contributed to the design of the study, collected the samples, recorded clinical data, and wrote the manuscript with input from the other authors. SK contributed to the design of the study, analyzed the clinical data, helped interpret the results, and wrote the manuscript with input from the other authors. AC contributed to the design of the study, helped interpret the results, and wrote the manuscript with input from the other authors. TC helped to collect the samples and recorded clinical data. MS contributed to the design of the study, performed biochemical analysis and statistical analysis, and helped interpret the results. All authors reviewed and approved the submitted manuscript.

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Correspondence to Nur Balci.

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Balci, N., Kurgan, Ş., Çekici, A. et al. Free amino acid composition of saliva in patients with healthy periodontium and periodontitis. Clin Oral Invest 25, 4175–4183 (2021). https://doi.org/10.1007/s00784-021-03977-7

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