We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P < 0.05) lower than that in infant mice administered saline (control group) (10 2.48 ؎ 10 0.31 and 10 2.78 ؎ 10 0.4 , respectively). Further, the survival rate of the L. casei Shirota group was significantly (P < 0.05) higher than that of the control group (14.3 versus 40.0%). One day after infection, pulmonary NK cell activity and interleukin-12 production by mediastinal lymph node cells of mice in the L. casei Shirota group were significantly greater than those of mice in the control group. These findings suggest that oral administration of L. casei Shirota activates the immature immune system of neonatal and infant mice and protects against IFV infection. Therefore, oral administration of L. casei Shirota may accelerate the innate immune response of the respiratory tract and protect against various respiratory infections in neonates, infants, and children, a high risk group for viral and bacterial infections.Influenza is an acute viral respiratory infection that results in high morbidity and significant mortality (3, 10). In particular, influenza infection sometimes causes pneumonia in older adults and encephalitis or encephalopathy in infants and children (9). It is important to reduce excess influenza deaths in older adults, infants, and children. It has been reported that, since the immune response, particularly cellular immunity, declines in older adults and the immune system in infants and children is immature, these individuals have increased susceptibility to influenza virus (IFV) infection.Lactic acid bacteria and their products have beneficial health effects on host homeostasis, including activation of the immune system (7,8). Lactobacillus casei strain Shirota, a member of the lactic acid bacteria, was originally isolated from the human intestine and has been used commercially for a long time to produce fermented milk. Various aspects of the effects of L. casei Shirota have been studied intensively. L. casei Shirota exhibits marked antitumor activity against transplantable tumors and 3-methylcholanthrene-induced tumors (17, 23) and anti-infectious activity against various pathogens such as Listeria monocytogenes and herpes simplex virus (20,28). In a human study, it was demonstrated that oral administration of L. casei Shirota to surgical patients suppressed the recurrence of superficial bladder cancer in a double-blind clinical trial (2). Further, we have previously reported that oral administration of L. casei Shirota to aged mice activates their weakened cellular immune system and reduces the nasal IFV titer in a model of upper respiratory IFV infection.The purpose of the present study was to invest...

We investigated whether oral administration of Lactobacillus casei strain Shirota activates the cellular immune system and ameliorates influenza virus (IFV) titer in the nasal site in upper respiratory IFV infection by using aged mice. Natural killer activity of splenocytes and lung cells of aged mice fed an L. casei strain Shirota diet (L. casei strain Shirota group) was significantly (P < 0.01 and P < 0.05) increased compared to those fed a control diet (control group). The increases were 1.5-and 2.5-fold, respectively. In aged mice fed an L. casei strain Shirota diet, potent induction of gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-␥ and TNF-␣ production increased 12-and 3.5-fold, respectively. In this model of upper respiratory IFV infection, the titer of IFV in the nasal washings of aged mice fed an L. casei strain Shirota diet was significantly (P < 0.05) lower than that in aged mice fed a control diet (10 1.6 ؎ 0.6 and 10 2.2 ؎ 0.5 , respectively). These findings suggest that oral administration of L. casei strain Shirota activates not only systemic cellular immunity but also local cellular immunity and that it ameliorates IFV infection.Influenza is an acute viral respiratory infection that results in high morbidity and significant mortality (2, 10). In particular, influenza infection causes deaths in older adults (5). It is presumed that declining host immune responses, particularly cellular immunity, account for the increased susceptibility to influenza virus (IFV) infection of the aged. Several studies have shown diminished natural killer (NK) cell and cytotoxic Tlymphocyte activity in aged mice compared to those in the young mice (3,14). An increased susceptibility to IFV infection associated with the impaired immune function of T helper 1 (Th1) cells has also been reported in the senescence-accelerated mouse (7).Lactic acid bacteria and their products are reported to have beneficial effects on host homeostasis, including activation of the immune system (8, 9). Lactobacillus casei strain Shirota, a lactic acid bacteria, was originally isolated from the human intestine and has been used commercially for a long time to produce fermented milk. Various aspects of the effects of L. casei strain Shirota have been studied intensively. L. casei strain Shirota exhibits marked activity against transplantable and 3-methylcholanthrene-induced tumors (13, 20) and antiinfectious activity against various pathogens such as Listeria monocytogenes and herpes simplex virus (17, 25). We have previously reported that intranasal administration of L. casei strain Shirota enhanced cellular immunity in the respiratory tract and protected against IFV infection in mice (12).The purpose of the present study was to investigate whether oral administration of L. casei strain Shirota activates not only the systemic immune system but also the local immune system and whether it ameliorates IFV infection in the upper respirator...

In mice administered Lactobacillus casei strain Shirota (LcS) intranasally, potent induction of interleukin 12, gamma interferon, and tumor necrosis factor alpha, which play a very important role in excluding influenza virus (IFV), was evident in mediastinal lymph node cells. In this model of upper respiratory IFV infection, the titers of virus in the nasal wash of mice inoculated with 200 g of LcS for three consecutive days (LcS 200 group) before infection were significantly (P < 0.01) lower than those of mice not inoculated with LcS (control group) (10 0.9 ؎ 0.6 versus 10 2.1 ؎ 1.0). The IFV titer was decreased to about 1/10 of the control level. Using this infection model with modifications, we investigated whether the survival rate of mice was increased by intranasal administration of LcS. The survival rate of the mice in the LcS 200 group was significantly (P < 0.05) greater than that of the mice in the control group (69% versus 15%). It seems that the decrease in the titer of virus in the upper respiratory tract to 1/10 of the control level was important in preventing death. These findings suggest that intranasal administration of LcS enhances cellular immunity in the respiratory tract and protects against influenza virus infection.Influenza virus (IFV) infections continue to be a significant public health problem for which improved therapies and preventive treatments are urgently needed. Some of the therapeutic approaches used thus far have included antiviral compounds (9, 23), vaccines (10), and biological response modifiers (2,8,21). In recent years, there has been an increased tendency in modern medicine to apply preventive treatments involving the use of probiotics, such as Lactobacillus or Bifidobacterium.A probiotic is defined by Havenaar (7) as a monoculture or mixed culture of living microorganisms that is applied to animals or man, beneficially affecting the host by improving the properties of the indigenous gastrointestinal microflora. It is restricted to products that contain living microorganisms, improve the health and well-being of man or animals, and can have an effect on all host mucosal surfaces, including the mouth, gastrointestinal tract (e.g., applied in food), upper respiratory tract (e.g., applied as an aerosol), or urogenital tract (local application). However, recently the definition of a probiotic has become even broader, and it has been concluded that dead bacteria and metabolic products with immunostimulatory activity or activity in prevention of infection by pathogens should be included in this category. Lactic acid bacteria and their products have been reported to have beneficial effects on host homeostasis and are effective in activating the immune system (4, 5).Lactobacillus casei strain Shirota (LcS), a member of the lactic acid bacteria, was originally isolated from the human intestine and has been used commercially for a long time to produce fermented milk. Various aspects of the effects of LcS have been studied intensively. LcS exhibits remarkable activity against syngen...

Mice fed Bifidobacterium breve YIT4064 and immunized orally with influenza virus were more strongly protected against influenza virus infection of the lower respiratory tract than ones immunized with influenza virus only. The number of mice with enhanced anti-influenza virus immunoglobulin G (IgG) in serum upon oral administration of B. breve YIT4064 and oral immunization with influenza virus was significantly greater than that upon oral immunization with influenza virus only. These findings demonstrated that the oral administration of B. breve YIT4064 increased anti-influenza virus IgG antibodies in serum and protected against influenza virus infection. The oral administration of B. breve YIT4064 may enhance antigen-specific IgG against various pathogenic antigens taken orally and induce protection against various virus infections.

Mouse pups born to and nursed by dams fed Bifidobacterium breve YIT4064 and immunized orally with rotavirus were more strongly protected against rotavirus-induced diarrhea than those born to and nursed by dams immunized with rotavirus only. The level of antirotavirus IgA in milk of dams fed B. breve YIT4064 and immunized orally with rotavirus was significantly higher than that of dams immunized with rotavirus only. The antirotavirus IgA level in feces of dams immunized orally with rotavirus was also increased by oral administration of B. breve YIT4064. These findings demonstrate that oral administration of B. breve YIT4064 enhanced antigen-specific IgA antibody in the mammary gland and in the intestine. Oral administration of B. breve YIT4064 may enhance antigen-specific IgA antibody against various pathogenic antigens taken orally and induce protection against infections in various mucosal tissues.