Extract of metabolic products of Bacillus subtilis AK augments natural killer cell cytotoxic activity

Abstract

Aim: Natural killer (NK) cells play an important role in immune surveillance against viral diseases and cancer. Probiotics, live bacteria beneficial to human health, and some bacterial metabolic products are reported to augment NK cell activity and possibly result in the prevention of tumor development. The aim of this study was to investigate the effect of an extract of metabolic products of Bacillus subtilis AK (EMBSAK), a selected clone of Bacillus subtilis natto, on NK cell activity in human volunteers and mice. Methods: In the human study, healthy volunteers ingested an EMBSAK-containing commercially available product, SARABAGAN, for 7 days. In the mice study, BALB/c wild-type (WT), interferon (IFN)-γ-deficient (IFN-γ−/−) and RAG 2-deficient (RAG −/−) mice were given oral SARABAGAN 80 mg/kg/day for 7 days. Cytotoxic activity and NK cell number were then examined on 51Cr release assay and flow cytometry, respectively. Results: Oral EMBSAK frequently increased NK cell cytotoxicity, but not NK cell population, in human volunteers in a dose-dependent manner. Moreover, oral EMBSAK augmented NK cell cytotoxicity, but not NK cell number and population, in WT and RAG 2-deficient, but not IFN-γ-deficient, mice. This suggests that supplemental intake of EMBSAK enhances NK cell cytotoxic activity, but not cell number, depending on IFN-γ but not on acquired immune cells. Conclusion: EMBSAK may be useful to prevent infectious and malignant disease via activation of NK cell cytotoxicity.