In mice administeredLactobacillus caseistrain 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 μg 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.

We investigated whether oral administration ofLactobacillus caseistrain 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 anL. caseistrain Shirota diet (L.caseistrain Shirota group) was significantly (P< 0.01 andP< 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 XL.caseistrain Shirota diet, potent induction of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-γ and TNF-α 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 anL.caseistrain 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 ofL.caseistrain Shirota activates not only systemic cellular immunity but also local cellular immunity and that it ameliorates IFV infection.

Various benefits of probiotics to the host have been shown in numerous human clinical trials. These organisms have been proposed to act by improving the balance of the gut microbiota and enhancing the production of short-chain fatty acids, as well as by interacting with host cells in the gastrointestinal tract, including immune cells, nerve cells, and endocrine cells. Although the stimulation of host cells by probiotics and subsequent signaling have been explained by in vitro experiments and animal studies, there has been some skepticism as to whether probiotics can actually interact with host cells in the human gastrointestinal tract, where miscellaneous indigenous bacteria coexist. Most recently, it has been shown that the ileal microbiota in humans after consumption of a fermented milk is occupied by probiotics for several hours, indicating that there is adequate opportunity for the ingested strain to stimulate the host cells continuously over a period of time. As the dynamics of ingested probiotics in the human gastrointestinal tract become clearer, further progress in this research area is expected to elucidate their behavior within the tract, as well as the mechanism of their physiological effects on the host.

The natural killer (NK) activity of blood mononuclear cells and splenocytes in aged mice fed on a diet containing Lactobacillus casei strain Shirota (LcS group) was significantly (P < 0.01) higher than that in mice fed on a diet without LcS. In the LcS group, there was a significant positive correlation (r = 0.63, P < 0.01) between the NK activity of blood mononuclear cells and the NK activity of splenocytes.

The protective effect of isoflavones on skin damage from ultraviolet (UV) radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05). The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05). Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05). Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05). These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice.