Human Systemic Immune Response to Ingestion of the Oral Probiotic Streptococcus salivarius BLIS K12

Probiotics Antimicrob Proteins. 2021 Dec;13(6):1521-1529. doi: 10.1007/s12602-021-09822-3. Epub 2021 Jul 19.


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.

Keywords: Cytokines; Immune; Oral tolerance; Probiotic; Regulatory T cells; S. salivarius.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / immunology
  • Eating
  • Humans
  • Immunity*
  • Lymphocytes / immunology
  • Probiotics*
  • Streptococcus salivarius* / immunology


  • Cytokines