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

Microbiol Immunol. 2015 Jan;59(1):1-12. doi: 10.1111/1348-0421.12210.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Bifidobacterium / immunology*
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Killer Cells, Natural / immunology*
  • Lung / immunology
  • Lung / pathology
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / pathology
  • Probiotics / administration & dosage*
  • Spleen / immunology
  • Sulfalene
  • Survival Analysis


  • Cytokines
  • Sulfalene