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Colonization, safety, and tolerability study of the Streptococcus salivarius 24SMBc nasal spray for its application in upper respiratory tract infections

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Abstract

Streptococcus salivarius, a non-pathogenic species and the predominant colonizer of the oral microbiota, finds a wide application in the prevention of upper respiratory tract infections, also reducing the frequency of their main pathogens. In this pilot study, the primary objective was to evaluate the safety and tolerability of a nasal spray, S. salivarius 24SMBc, as a medical device in a clinical study involving 20 healthy adult subjects. The secondary aim was to determine the ability of colonization assessed by molecular fingerprinting. Twenty healthy adult subjects, aged between 30 and 54 years, without a medical history of recurrent otitis media, were enrolled. All patient characteristics fulfilled the inclusion criteria. All subjects were treated daily for 3 days with the nasal spray containing S. salivarius 24SMBc at a concentration of 5 × 109 colony-forming units (CFU)/ml. The persistence of S. salivarius in the nasopharynx was investigated by the antagonism test and random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). The tolerability and safety were clinically assessed by clinical examinations during treatment. Our results demonstrate the capability of S. salivarius 24SMBc to colonize the rhinopharynx tissues in 95 % of subjects and persist in 55 % of them after 6 days from the last dose of the formulation, maintaining a concentration of 105 CFU/ml. The treatment was well tolerated by all healthy patients and no adverse effects were found. The topical application of streptococcal probiotics is a relatively undeveloped field but is becoming an attractive approach for both prevention and therapy, especially for pediatric age patients. S. salivarius 24SMBc possess characteristics making this strain suitable for use in bacteriotherapy.

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References

  1. Lenoir-Wijnkoop I, Sanders ME, Cabana MD, Caglar E, Corthier G, Rayes N, Sherman PM, Timmerman HM, Vaneechoutte M, Van Loo J, Wolvers DA (2007) Probiotic and prebiotic influence beyond the intestinal tract. Nutr Rev 11(65):469–489

    Article  Google Scholar 

  2. Gareau MG, Sherman PM, Walker WA (2010) Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol 7(9):503–514, review

    Article  PubMed  Google Scholar 

  3. Ashraf R, Shah NP (2014) Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci Nutr 54:938–956

    Article  CAS  PubMed  Google Scholar 

  4. Koboziev I, Reinoso Webb C, Furr KL, Grisham MB (2014) Role of the enteric microbiota in intestinal homeostasis and inflammation. Free Radic Biol Med 68:122–133

    Article  CAS  PubMed  Google Scholar 

  5. Liu S, Hu P, Du X, Zhou T, Pei X (2013) Lactobacillus rhamnosus GG supplementation for preventing respiratory infections in children: a meta-analysis of randomized, placebo-controlled trials. Indian Pediatr 50(4):377–381

    Article  PubMed  Google Scholar 

  6. Cohen R, Martin E, de La Rocque F, Thollot F, Pecquet S, Werner A, Boucherat M, Varon E, Bingen E, Levy C (2013) Probiotics and prebiotics in preventing episodes of acute otitis media in high-risk children: a randomized, double-blind, placebo-controlled study. Pediatr Infect Dis J 32(8):810–814

    PubMed  Google Scholar 

  7. Hatakka K, Blomgren K, Pohjavuori S, Kaijalainen T, Poussa T, Leinonen M, Korpela R, Pitkäranta A (2007) Treatment of acute otitis media with probiotics in otitis-prone children a double-blind, placebo-controlled randomised study. Clin Nutr 26(3):314–321

  8. Wescombe PA, Hale JD, Heng NC, Tagg JR (2012) Developing oral probiotics from Streptococcus salivarius. Future Microbiol 7:1355–1371

    Article  CAS  PubMed  Google Scholar 

  9. Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, Bavcar A, Grasso D, Barbiero C, Tamburlini G (2012) Burden of disease caused by otitis media: systematic review and global estimates. PLoS One 7:e36226

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, Joffe MD, Miller DT, Rosenfeld RM, Sevilla XD, Schwartz RH, Thomas PA, Tunkel DE; American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media (2013) The diagnosis and management of acute otitis media. Pediatrics 131:e964–e999

    Article  PubMed  Google Scholar 

  11. Marchisio P, Claut L, Rognoni A, Esposito S, Passali D, Bellussi L, Drago L, Pozzi G, Mannelli S, Schito G, Principi N (2003) Differences in nasopharyngeal bacterial flora in children with nonsevere recurrent acute otitis media and chronic otitis media with effusion: implications for management. Pediatr Infect Dis J 22:262–268

    PubMed  Google Scholar 

  12. John M, Dunne EM, Licciardi PV, Satzke C, Wijburg O, Robins-Browne RM, O’Leary S (2013) Otitis media among high-risk populations: can probiotics inhibit Streptococcus pneumoniae colonisation and the risk of disease? Eur J Clin Microbiol Infect Dis 32(9):1101–1110, review

    Article  CAS  PubMed  Google Scholar 

  13. Tagg JR (2004) Prevention of streptococcal pharyngitis by anti-Streptococcus pyogenes bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius. Indian J Med Res 119(Suppl):13–16

    CAS  PubMed  Google Scholar 

  14. Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR (2006) A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol 100(4):754–764

    Article  CAS  PubMed  Google Scholar 

  15. Santagati M, Scillato M, Patanè F, Aiello C, Stefani S (2012) Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol Med Microbiol 65(1):23–31

    Article  CAS  PubMed  Google Scholar 

  16. Stol K, Verhaegh SJ, Graamans K, Engel JA, Sturm PD, Melchers WJ, Meis JF, Warris A, Hays JP, Hermans PW (2013) Microbial profiling does not differentiate between childhood recurrent acute otitis media and chronic otitis media with effusion. Int J Pediatr Otorhinolaryngol 77(4):488–493

    Article  PubMed  Google Scholar 

  17. Célind J, Södermark L, Hjalmarson O (2014) Adherence to treatment guidelines for acute otitis media in children. The necessity of an effective strategy of guideline implementation. Int J Pediatr Otorhinolaryngol 78(7):1128–1132

    Article  PubMed  Google Scholar 

  18. Tagg JR, Bannister LV (1979) “Fingerprinting” beta-haemolytic streptococci by their production of and sensitivity to bacteriocine-like inhibitors. J Med Microbiol 12:397–411

    Article  CAS  PubMed  Google Scholar 

  19. Truong TL, Ménard C, Mouton C, Trahan L (2000) Identification of mutans and other oral streptococci by random amplified polymorphic DNA analysis. J Med Microbiol 49:63–71

    Article  CAS  PubMed  Google Scholar 

  20. Conticello S, Saita V, La Mantia I, Ferlito S (1989) Endoscopy of the eustachian tube: use of the fiberscope and the telescope. Arch Otorhinolaryngol 246:256–258, Sprinter-Verlag Ed

    Article  CAS  PubMed  Google Scholar 

  21. Serra A, Grillo C, La Mantia I, Cipri R, Vancheri M, Saita V (1992) Naso-pharyngo-laryngoscopie et rhinomanométrie avec endoscope flexible dans l’étude de l’hypertrophie adénoïde. Acta Endoscopica Belg 22:381–384

    Article  Google Scholar 

  22. Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214

    Article  Google Scholar 

  23. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE (2005) Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 43(11):5721–5732

    Article  PubMed Central  PubMed  Google Scholar 

  24. Soccol CR, Porto de Souza Vandenberghe L, Spier MR, Pedroni Medeiros AB, Yamaguishi CT, De Dea Lindner J, Pandey A, Thomaz-Soccol V (2010) The potential of probiotics: a review. Food Technol Biotech 48(4):413–434

    CAS  Google Scholar 

  25. Caglar E, Kargul B, Tanboga I (2005) Bacteriotherapy and probiotics’ role on oral health. Oral Dis 11(3):131–137

    Article  CAS  PubMed  Google Scholar 

  26. Di Pierro F, Colombo M, Zanvit A, Risso P, Rottoli AS (2014) Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf 6:15–20

    Article  PubMed Central  PubMed  Google Scholar 

  27. Walls T, Power D, Tagg J (2003) Bacteriocin-like inhibitory substance (BLIS) production by the normal flora of the nasopharynx: potential to protect against otitis media? J Med Microbiol 52(Pt 9):829–833

    Article  CAS  PubMed  Google Scholar 

  28. Roos K, Håkansson EG, Holm S (2001) Effect of recolonisation with “interfering” alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ 322(7280):210–212

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Tano K, Grahn Håkansson E, Holm SE, Hellström S (2002) A nasal spray with alpha-haemolytic streptococci as long term prophylaxis against recurrent otitis media. Int J Pediatr Otorhinolaryngol 62(1):17–23

    Article  PubMed  Google Scholar 

  30. Skovbjerg S, Roos K, Holm SE, Grahn Håkansson E, Nowrouzian F, Ivarsson M, Adlerberth I, Wold AE (2009) Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media. Arch Dis Child 94(2):92–98

    Article  CAS  PubMed  Google Scholar 

  31. Gao Z, Kang Y, Yu J, Ren L (2014) Human pharyngeal microbiome may play a protective role in respiratory tract infections. Genomics Proteomics Bioinformatics 12(3):144–150

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a project funded by the Italian Ministry of Education, University and Research (MIUR), PON_02589 and a research grant from DMG Italia. The nasal spray as a medical device was kindly provided by DMG Italia. We thank the Scientific Bureau of the University of Catania for the language support.

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The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. LabMMAR, Department of Biomedical and Biotechnological Sciences, Section of Microbiology, University of Catania, Via Androne 81, 95124, Catania, Italy

    M. Santagati, M. Scillato, N. Muscaridola, V. Metoldo & S. Stefani

  2. Department of Medical Sciences, Surgical and Advanced Technologies, GF Ingrassia, University of Catania, Catania, Italy

    I. La Mantia

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  1. M. Santagati
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  2. M. Scillato
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  3. N. Muscaridola
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  5. I. La Mantia
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  6. S. Stefani
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Correspondence to M. Santagati.

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Santagati, M., Scillato, M., Muscaridola, N. et al. Colonization, safety, and tolerability study of the Streptococcus salivarius 24SMBc nasal spray for its application in upper respiratory tract infections. Eur J Clin Microbiol Infect Dis 34, 2075–2080 (2015). https://doi.org/10.1007/s10096-015-2454-2

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  • DOI: https://doi.org/10.1007/s10096-015-2454-2

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