The effect of muramyl peptide on the microbial landscape of the oral cavity

• Svetlana V. Guryanova
• Borisova O.Yu.
• Kolesnikova N.V.
• Nino L. Lezhava
• Ivan G. Kozlov
• Georgii O. Gudima

Abstract

Introduction. The composition of the microbiota of the oral cavity is crucial in the formation of a normal biocenosis, its imbalance can be the cause of pathophysiological processes not only of the oral cavity, but also of the whole organism. Disorder of the microbiome diversity in the oral cavity, a quantitative decrease in the presence of opportunistic microflora contributes to the population of pathogenic strains and correlates with various diseases of the oral cavity, such as caries and periodontitis, diseases of the gastrointestinal tract and bronchopulmonary system.

The aim of the study was to determine the effect of muramyl peptide GMDP (Likopid® 1 mg) on the microbial landscape of the oral cavity of healthy volunteers.

Material and methods. With informed consent, 48 healthy volunteers aged 18-23 years were taken oral fluid before taking the GMDP (prophylactics with Likopid^® 1 mg) and 4 days after a 10-day course, 1 tablet sublingually 1 time per day. A microbiological study of the oral fluid was carried out using gas chromato-mass spectrometry of microbial markers.

Results. The use of an immunomodulating agent based on muramyl peptide increases the diversity of the microflora of the oral cavity, and reduces in quantitative terms Candida albicans, Clostridium difficile and Porphyromonas gingivalis.

Conclusion. The use of an immunomodulating agent based on muramyl peptide is advisable for the formation of a normal balanced microbiocenosis in order to prevent pathogen colonization.

Keywords:microbiota; oral cavity; muramyl peptide; GMDP; immunomodulators, mucosal immunity

References

1. Hooper L.V., Littman D.R., Macpherson A.J. Interactions Between the Microbiota and the Immune System. Science. 2012; 336: 1268-73.

2. Ley R.E., Peterson D.A., Gordon J.I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006; 124: 837-48.

3. Dethlefsen L., McFall-Ngai M., Relman D.A. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature. 2007; 449: 811-8.

4. Macpherson A.J., Harris N.L. Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 2004; 4: 478-85.

5. Lima M. T., Andrade A.C.S.P., Oliveira G.P., Calixto R.S., Oliveira D.B., Souza E.L.S., et al. Microbiota is an essential element for mice to initiate a protective immunity against Vaccinia virus. FEMS Microbiology Ecology. 2016; 92 (2): fiv147.

6. Turnbaugh PJ, Backhed F., Fulton L., Gordon J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008; 3: 213-23.

7. Ley R.E., et al. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA. 2005; 102: 11070-5.

8. Leystra A.A., Clapper M.L. Gut Microbiota Influences Experimental Outcomes in Mouse Models of Colorectal Cancer. Genes. 2019; 10 (11) 900; 1-20. doi: https://doi.org/10.3390/genes10110900

9. Uronis J.M., Muhlbauer M., Herfarth H.H., Rubinas T.C., Jones G.S., et al. Modulation of the intestinal microbiota alters colitis associated colorectal cancer susceptibility. PLoS ONE. 2009; 4: e6026.

10. Buffington S.A., Di Prisco G.V., Auchtung T.A., Ajami N.J., Petrosino J.F., Costa-Mattioli M. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell. 2016; 165: 1762-75. doi: 10.1016/j.cell.2016.06.001

11. Goodacre R. Metabolomics of a superorganism. J. Nutr. 2007; 137 (1 Suppl): 259S-66S.

12. Lederberg J. Infectious history. Science. 2000; 288 (5464): 287-93.

13. Carroll I.M., Threadgill D.W., Threadgill D.S. The gastrointestinal microbiome: a malleable, third genome of mammals. Mamm. Genome. 2009; 20 (7): 395-403. doi: 10.1007/s00335-009-9204-7

14. Li J., Jia H., Cai X., Zhong H., Feng Q., Sunagawa S., et al. An integrated catalog of reference genes in the human gut microbi-ome. Nat. Biotechnol. 2014; 32: 834-41. doi: 10.1038/nbt.2942

15. Afanasyev S., Aleshkin V.A., VoropaevaE.A., Afanasyev M.S., Slobodenyuk V.V., Karaulov A.V. Microbiocenoses of open cavities and mucosal immunity. Effective pharmacotherapy. 2013; 27: 6-11. (in Russian)

16. Okereke I.C., MillerA.L., Hamilton C.F., BoothA.L., Reep G.L., Andersen C.L., et al. Microbiota of the Oropharynx and Endoscope Compared to the Esophagus. Sci Rep. 2019; 9: 10201. doi: 10.1038/s41598-019-46747-y

17. Lemon K.P., Klepac-Ceraj V., Schiffer H.K., Brodie E.L., Lynch S.V., et al. Comparative analyses of the bacterial microbiota of the human nostril and oropharynx. mBio. 2010; 1 (3): e00129-10. doi: 10.1128/mBio.00129-10

18. Zaura E., Keijser B.J., Huse S.M., Crielaard W. Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol. 2009; 9: 259. doi: 10.1186/1471-2180-9-259

19. Burmistrova A.L., Filippova Yu.Yu., Nokhrin D.Yu., Timofeeva A.V. Microbial society of environmental niche: oral cavity of the healthy children. Russian Journal of Infection and Immunity. Infection and immunity. 2018; 8 (1): 54-60. doi: 10.15789/2220-7619-2018-1-54-60

20. Borisova O.Yu., Aleshkin V.A., Pimenova A.S., Krukov A.I., Kunelskaya N.L., Gurov A.V., et al. Microbial landscape of microflora of a pharynx at patients with tonsillit’s pathology. Russian Journal of Infection and Immunity. Infection and immunity. 2015; 5 (3): 225-32. doi: 10.15789/2220-7619-2015-3-225-232 (in Russian)

21. Segata N., Haake S.K., Mannon P., Lemon K.P., Waldron L., Gevers D., et al. Composition of the adult digestive tract bacterial mi-crobiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012; 13 (6): R42. doi: 10.1186/gb-2012-13-6-r42

22. Girardin S.E., Sansonetti P.J., Philpott D.J. Intracellular vs extracellular recognition of pathogens-common concepts in mammals and flies. Trends Microbiol. 2002; 10 (4): 193-9.

23. Negroni A., Pierdomenico M., Cucchiara S., Stronati L. NOD2 and inflammation: current insights. J. Inflamm Res. 2018; 11: 49-60. doi: 10.2147/JIR.S137606

24. Biswas A., Liu Y.J., Hao L., Mizoguchi A., Salzman N.H., Bevins C.L., Kobayashi K.S. Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation ofthe ileum. Proc. Natl. Acad. Sci USA. 2010; 107 (33): 14739-44. doi: 10.1073/pnas.1003363107

25. NikitushkinV.D.,Demina G.R., ShleevaM.O., KaprelyantsA.S., Guryanova S.V., Ruggiero A., Berisio R. A product of RpfB and RipA joint enzymatic action promotes the resuscitation of dormant mycobacteria. FEBS Journal. 2015; 282 (13): 2500-11.

26. Luginova E.F., Starostin V.P., Kapustina M.I. Clinical and laboratory manifestations of infection with drug-resistant mycobacterium tuberculosis in children and the effectiveness of comprehensive preventive treatment. Far Eastern Medical Journal. 2010. (1): 25-28. (in Russian)

27. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. 2013; 310: 2191-4.

28. Osipov G.A., Boiko N.B., Fedosova N.F., Kasikhina S.A., Lyadov K.V. Comparative gas chromatography-mass spectrometry study of the composition of microbial chemical markers in feces. Microb. Ecol. Health Dis. 2009; 21: 159-71. doi: 10.3109/08910600903462657

29. Naito M., Hirakawa H., Yamashita A., et al. Determination of the Genome Sequence of Porphyromonas gingivalis Strain ATCC 33277 and Genomic Comparison with Strain W83 Revealed Extensive Genome Rearrangements in P. gingivalis. DNA Research. 2008; 15 (4): 215-25.

30. Potempa J., Dragunow M., Curtis M.A., Faull R.L.M., Reynolds E.C., Walker G.D., et al. Porphyromonas gingivalis in Alzheimer disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances. 2019; 5 (1): eaau3333. doi: 10.1126/sciadv.aau3333

31. Meshcheryakova E., Makarov E., Andronova T., Ivanov V., Philpott D. Evidence for correlation between the intensities of adjuvant effects and NOD2 activation by monomeric, dimeric and lipo-phylic derivatives of N-acetylglucosaminyl-N-acetylmuramyl peptides. Vaccine. 2007; 25 (23): 4515-20.

32. Al Nabhani Z., Dietrich G., Hugot J.P., Barreau F. Nod2: The intestinal gate keeper. PLoS Pathog. 2017; 13 (3): e1006177. doi: 10.1371/journal.ppat.1006177

33. Laman A.G., Lathe R., Shepelyakovskaya A.O., Gartseva A., Brovko F.A., Guryanova S., et al. Muramyl peptides activate innate immunity conjointly via YB1 and NOD2. Innate Immun. 2016; 30: 41-9. doi: 10.1177/1753425916668982

34. Kolesnikova N.V., Kozlov I.G., Guryanova S.V., Kokov E.A., Andronova T.M. Clinical and immunological efficacy and prospects for the use of muramyl dipeptides in the treatment of atopic diseases. Medical immunology. 2016. 18 (1): 15-20. (in Russian)

35. Guryanova S.V., Kozlov I.G., Meshcheryakova E.A., Alekseeva L.O., Andronova T.M. Investigation into the influence of glucos-aminylmuramyl dipeptide on the normalization of Th1/Th2 balance in patients with atopic bronchial asthma. Immunologiya. 2009; (5): 305-8. (in Russian)

36. Guryanova S., Udzhukhu V., Kubylinsky A. Pathogenetic therapy of psoriasis by muramyl peptide. Frontiers in Immunology. 2019; 10: 1275-83. doi: 10.3389/fimmu.2019.01275

37. Manapova E.R., Fazylov V.Ch., Guryanova S.V. Cytopenias and their correction during antiviral therapy of chronic hepatitis C in patients with genotype 1. Problems of Virology, Russian journal. 2017; 62 (4): 174-8. (in Russian)

38. Kozlov I.G., Voronina E.V., Valyakina T.I., Simonova M.A., Guryanova S.V., Meshcheryakova E.A., Andronova T.M. Lycopid in tumor immunotherapy: a review of experimental studies (literature review). Questions of hematology / oncology and immunopathology in pediatrics. 2011; 10 (2): 32-8. (in Russian)

39. Rabinovich O.F., Rabinovich I.M., Abramova E.S. The use of lycopide in the treatment of dysbiosis of the oral cavity. Dentistry. 2013; 92 (1): 40-2. (in Russian)

40. Nesterova I.V., Kolesnikova N.V., Nedelko N.A. Method for immunocorrection of lycopide with local immunity disorders in patients with acute odontogenic periostitis. Dentist practitioner. 2006; 12 (148): 30-1. (in Russian)

41. Guryanova S.V, Guryanova A.S. Modern Approach to Systems Biology, chapter in: Biological Networks and Pathway Analysis. Springer/Eds.: Tatarinova T.V., Nikolsky Yu. Publ. Humana Press Inc., Totowa, NJ, United States. 2017. doi: 10.1007/978-1-4939-7027-8_2

42. Namasivayam A.A., Peitsch M.C., Racero M.G., Biryukov M., Talikka M., Perez M.B., et al. Community-Reviewed Biological Network Models for Toxicology and Drug Discovery Applications. Gene Regulation and Systems Biology. 2016; 12 (10): 51-66. doi: 10.4137/GRSB.S39076

43. Peterson D.A., Frank D.N., Pace N.R., Gordon J.I. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host. Microbe. 2008; 3: 417-27.

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