Abstract
Streptococcus salivarius K12 is an oral probiotic known to contribute to protection against oral pathogenic bacteria in humans. Studies of immune responses to S. salivarius K12 have focused on the oral cavity, and systemic immune responses have not yet been reported. The aim of this study was to identify acute systemic immune responses to the commercial product, S. salivarius BLIS K12, in a double-blinded, placebo-controlled human clinical trial. It was hypothesised that consumption of S. salivarius BLIS K12 would induce an anti-inflammatory response and a decrease in pro-inflammatory cytokines. Blood samples were obtained from participants prior to a single dose of S. salivarius BLIS K12 or a placebo and then secondary blood samples were obtained 24 h and 7 days post-consumption. Samples were analysed using multi-parametric flow cytometry, to quantify immune cell frequency changes, and by a LEGENDplex assay of human inflammatory cytokines. Consumption of S. salivarius BLIS K12 was associated with increased levels of IL-8 at 24 h. The frequency of Tregs increased in samples taken 7 days after probiotic consumption, and IL-10 concentrations were higher at 7 days than 24 h after consumption. There was no difference in the frequency and/or activation of CD4+ T cells, CD8+ T cells, B cells and NK cells. Interestingly, there was an increase in IL-12, 7 days after the consumption of S. salivarius BLIS K12. Collectively, this research demonstrates that ingestion of the probiotic S. salivarius K12 can induce changes in the systemic immune response. The implications of the generation and type of immune response warrant further study to determine potential health benefits.
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Data Availability Statement
The datasets generated during and/or analysed during the current study are not publicly available due to limitations in the ethical consent process but are available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank Janet Rhodes and Jackson Treece for phlebotomy services and Nic West for advice on data analysis.
Funding
This work was made possible by a Research and Development Student grant from Callaghan Innovation, New Zealand.
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JH conceived the project, provided probiotics and contributed to writing. GL performed all experiments and analysis and wrote the manuscript. RAK conceived the project, had oversight of the project, contributed to data analysis and wrote the manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Human Ethics Committee of the University of Otago (Ref#H18/054).
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Informed consent was obtained from all individual participants included in the study.
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Informed consent to publish was obtained from all individual participants in the study.
Conflict of Interest
JDFH is an employee of Blis Technologies, the manufacturer of Streptococcus salivarius BLIS K12 probiotics.
GLL was an employee of Blis Technologies prior to commencing this work. Blis Technologies supported student fees for GL.
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Laws, G.L., Hale, J.D.F. & Kemp, R.A. Human Systemic Immune Response to Ingestion of the Oral Probiotic Streptococcus salivarius BLIS K12. Probiotics & Antimicro. Prot. 13, 1521–1529 (2021). https://doi.org/10.1007/s12602-021-09822-3
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DOI: https://doi.org/10.1007/s12602-021-09822-3
Keywords
- Probiotic
- Immune
- Oral tolerance
- Cytokines
- S. salivarius
- Regulatory T cells