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Consecutive oral administration of Bifidobacterium longum MM‐2 improves the defense system against influenza virus infection by enhancing natural killer cell activity in a murine model

  • 2015-01
  • Microbiology and Immunology 59(1)
    • Tomohiro Kawahara
    • Tadanobu Takahashi
    • Kenta Oishi
    • Hiromu Tanaka
    • M. Masuda
    • Shunsaku Takahashi
    • Maiko Takano
    • Tatsuya Kawakami
    • Keijo Fukushima
    • H. Kanazawa
    • Takashi Suzuki


Bifidobacterium, one of the major components of intestinal microflora, shows anti-influenza virus (IFV) potential as a probiotic, partly through enhancement of innate immunity by modulation of the intestinal immune system. Bifidobacterium longum MM-2 (MM-2), a very safe bacterium in humans, was isolated from healthy humans and its protective effect against IFV infection in a murine model shown. In mice that were intranasally inoculated with IFV, oral administration of MM-2 for 17 consecutive days improved clinical symptoms, reduced mortality, suppressed inflammation in the lower respiratory tract, and decreased virus titers, cell death, and pro-inflammatory cytokines such as IL-6 and TNF-α in bronchoalveolar lavage fluid. The anti-IFV mechanism of MM-2 involves innate immunity through significant increases in NK cell activities in the lungs and spleen and a significant increase in pulmonary gene expression of NK cell activators such as IFN-γ, IL-2, IL-12 and IL-18. Even in non-infected mice, MM-2 administration also induced significant enhancement of both IFN-γ production by Peyer's patch cells (PPs) and splenetic NK cell activity. Oral administration of MM-2 for 17 days activates systemic immunoreactivity in PPs, which contributes to innate immunity, including NK cell activation, resulting in an anti-IFV effect. MM-2 as a probiotic may function as a prophylactic agent in the management of an IFV epidemic.

Keywords: Bifidobacterium longum; influenza virus; natural killer cell; probiotics.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Bifidobacterium longum MM-2Activated Systemic Immunoreactivity in Peyer's PatchesBeneficial
Bifidobacterium longum MM-2Enhanced IFN-γ ProductionBeneficial
Bifidobacterium longum MM-2Improved Clinical Symptoms of InfluenzaBeneficial
Bifidobacterium longum MM-2Improved Splenetic NK Cell ActivityBeneficial
Bifidobacterium longum MM-2Increased Pulmonary NK Cell Activator Gene ExpressionBeneficial
Bifidobacterium longum MM-2Reduced Inflammation in the Lower Respiratory TractBeneficial
Bifidobacterium longum MM-2Reduced Mortality from Influenza InfectionBeneficial
Bifidobacterium longum MM-2Reduced Virus Titers in Bronchoalveolar Lavage FluidBeneficial

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