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Interferon Gamma Response in Human Saliva Following Exposure to the Oral Probiotic Streptococcus salivarius BLIS K12

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Abstract

Streptococcus salivarius BLIS K12 is a probiotic strain developed for application to the oral cavity. The strain was originally characterised for its in vitro antibacterial activity against the prominent oral pathogen Streptococcus pyogenes. More recent research has expanded its applications to include reducing halitosis, preventing otitis media and protecting against virus infections of the respiratory tract. A potential mechanism for this anti-viral activity could be the stimulation of salivary interferon gamma (IFN-γ) production in the oral cavity. The aim of this study was to investigate whether the ingestion of and oral cavity colonisation by S. salivarius BLIS K12 is associated with enhancement of IFN-γ levels in saliva. Application of ELISA demonstrated that consumption of S. salivarius BLIS K12 effected an increase in salivary IFN-γ, and this response was more consistent with use of viable cells than following ingestion of heat-killed S. salivarius BLIS K12. Interestingly, those subjects who more successfully colonised with S. salivarius BLIS K12 did not experience a relatively larger increase in their IFN-γ levels, indicating that the observed IFN-γ response occurs independently of colonisation efficacy. In summary, the consumption of S. salivarius BLIS K12 increases salivary levels of IFN-γ, an effect that may contribute to protection of the host against certain virus infections.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Hegarty JW, Guinane CM, Ross RP et al (2016) Bacteriocin production: a relatively unharnessed probiotic trait? https://doi.org/10.12688/f1000research.9615.1

  2. Anderson RC, Cookson AL, McNabb WC et al (2010) Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation. BMC Microbiol 10:1–11. https://doi.org/10.1186/1471-2180-10-316/FIGURES/4

    Article  Google Scholar 

  3. Kechagia M, Basoulis D, Konstantopoulou S et al (2013) Health benefits of probiotics: a review. ISRN Nutr 2013:1–7. https://doi.org/10.5402/2013/481651

    Article  CAS  Google Scholar 

  4. Ljungh Å, Wadström T (2006) Lactic acid bacteria as probiotics. Curr Issues Intestinal Microbiol 7:73–90

    CAS  Google Scholar 

  5. Tagg JR, Dierksen KP (2003) Bacterial replacement therapy: adapting ‘germ warfare’ to infection prevention. Trends Biotechnol 21(5):217–223. https://doi.org/10.1016/S0167-7799(03)00085-4

  6. Tagg JR (2004) Prevention of streptococcal pharyngitis by anti-Streptococcus pyogenes bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius. Indian J Microbiol 119:13

    CAS  Google Scholar 

  7. Burton JP, Chilcott CN, Wescombe PA, Tagg JR (2010) Extended safety data for the oral cavity probiotic Streptococcus salivarius K12. Probiotics Antimicrob Proteins 2:135–144. https://doi.org/10.1007/s12602-010-9045-4

    Article  CAS  PubMed  Google Scholar 

  8. Ishijima SA, Hayama K, Burton JP et al (2012) Effect of Streptococcus salivarius K12 on the in vitro growth of Candida albicans and its protective effect in an oral candidiasis model. Appl Environ Microbiol 78:2190–2199. https://doi.org/10.1128/AEM.07055-11

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  9. Laws GL, Hale JDF, Kemp RA (2021) Human systemic immune response to ingestion of the oral probiotic Streptococcus salivarius BLIS K12. Probiotics Antimicrob Proteins. https://doi.org/10.1007/s12602-021-09822-3

    Article  PubMed  Google Scholar 

  10. Cosseau C, Devine DA, Dullaghan E et al (2008) The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun 76:4163–4175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. MacDonald KW, Chanyi RM, Macklaim JM et al (2021) Streptococcus salivarius inhibits immune activation by periodontal disease pathogens. BMC Oral Health 21:245. https://doi.org/10.1186/s12903-021-01606-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hiscott J, Kwon H, Génin P (2001) Hostile takeovers: viral appropriation of the NF-kB pathway. J Clin Investig 107:143. https://doi.org/10.1172/JCI11918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang Q, Lin X, Xiang X et al (2021) Oropharyngeal probiotic ENT-K12 prevents respiratory tract infections among frontline medical staff fighting against COVID-19: a pilot study. Front Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2021.646184

    Article  PubMed  PubMed Central  Google Scholar 

  14. di Pierro F, Colombo M (2021) The administration of S. salivarius K12 to children may reduce the rate of SARS-CoV-2 infection. Minerva Med 112. https://doi.org/10.23736/S0026-4806.21.07487-5

  15. di Pierro F, Colombo M, Zanvit A, Rottoli AS (2016) Positive clinical outcomes derived from using Streptococcus salivarius K12 to prevent streptococcal pharyngotonsillitis in children: a pilot investigation. Drug Healthc Patient Saf 8:77–81. https://doi.org/10.2147/DHPS.S117214

    Article  PubMed  PubMed Central  Google Scholar 

  16. Guo H, Xiang X, Lin X et al (2022) Oropharyngeal probiotic ENT-K12 as an effective dietary intervention for children with recurrent respiratory tract infections during cold season. Front Nutr. https://doi.org/10.3389/fnut.2022.900448

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chilcott C, Crowley L, Kulkarni V et al (2005) Elevated levels of interferon gamma in human saliva following ingestion of Streptococcus salivarius K12. NZMS, Dunedin, New Zealand 22-25 November 2005

  18. Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-y: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189. https://doi.org/10.1189/jlb.0603252.Journal

    Article  CAS  PubMed  Google Scholar 

  19. Hu X, Herrero C, Li W-P et al (2002) Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation. Nat Immunol 3:859–866. https://doi.org/10.1038/ni828

    Article  CAS  PubMed  Google Scholar 

  20. Lowenstein CJ, Alley EW, Raval P et al (1993) Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon y and lipopolysaccharide. Biochemistry 90:9730–9734. https://doi.org/10.1073/pnas.90.20.9730

  21. Xie QW, Cho HJ, Calaycay J et al (1979) (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228. https://doi.org/10.1126/SCIENCE.1373522

    Article  ADS  Google Scholar 

  22. Tagg JR, Read RS, McGiven AR (1973) Bacteriocin of a group A streptococcus: partial purification and properties. Antimicrob Agents Chemother 4:214–221. https://doi.org/10.1128/aac.4.3.214

  23. Morse SA (1996) Medical Microbiology 4th edition 12

  24. Harris DP, Haynes L, Sayles PC et al (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1:475–482

    Article  CAS  PubMed  Google Scholar 

  25. Bouwer AL, Saunderson SC, Dunn AC et al (2013) Rapid interferon-gamma release from natural killer cells induced by a streptococcal commensal. 33:459–466. https://doi.org/10.1089/JIR.2012.0116

  26. MacDonald K, Chanyi R, Macklaim J et al (2021) Streptococcus salivarius inhibits immune activation by periodontal disease pathogens. BMC Oral Health. https://doi.org/10.1186/S12903-021-01606-Z

    Article  PubMed  PubMed Central  Google Scholar 

  27. Burton J, Chilcott C, Moore C et al (2006) A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol 100:754–764. https://doi.org/10.1111/J.1365-2672.2006.02837.X

    Article  CAS  PubMed  Google Scholar 

  28. Wescombe PA, Heng NCK, Burton JP et al (2009) Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probiotics. Future Microbiol 4:819–835

    Article  CAS  PubMed  Google Scholar 

  29. Hyink O, Wescombe PA, Upton M et al (2007) Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12. Appl Environ Microbiol. https://doi.org/10.1128/AEM.02265-06

    Article  PubMed  Google Scholar 

  30. Burton JP, Cowley S, Simon RR et al (2011) Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol 49:2356–2364. https://doi.org/10.1016/j.fct.2011.06.038

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

G.A.L. helped design the study, and ran the clinical trial and laboratory analysis. L.K.H. wrote the main manuscript text. J.R.T. contributed to the planning and assessment of results. J.D.F.H. designed the project and reviewed the results. All authors reviewed and contributed to writing.

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Correspondence to John D. F. Hale.

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Health and Disability Ethics Committee LRS/09/02/002/AM03.

Conflict of Interest

G.A.L., L.K.H., J.R.T. and J.D.F.H are/or were employees of Blis Technologies at the time of this research.

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Laws, G.A., Harold, L.K., Tagg, J.R. et al. Interferon Gamma Response in Human Saliva Following Exposure to the Oral Probiotic Streptococcus salivarius BLIS K12. Probiotics & Antimicro. Prot. 16, 93–98 (2024). https://doi.org/10.1007/s12602-022-10010-0

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