Diverse impact of a probiotic strain, Lacticaseibacillus paracasei Shirota, on peripheral mononuclear phagocytic cells in healthy Japanese office workers: a randomized, double-blind, controlled trial.

Mononuclear phagocytic cells (MPCs) are classified into monocytes (Mos)/macrophages and dendritic cells (DCs) based on their functions. Cells of MPCs lineage act as immune modulators by affecting effector cells, such as NK cells, T cells, and B cells. This study aimed to investigate the effects of Lacticaseibacillus paracasei strain Shirota (LcS) ingestion on peripheral MPCs, particularly on their expression of functional cell-surface molecules enhanced in healthy adults. Thus, twelve healthy office workers consumed a fermented milk drink containing 1.0 × 1011 cfu of LcS (LcS-FM) or a control unfermented milk drink (CM) once a day for 6 weeks. Peripheral blood mononuclear cells (PBMCs) were prepared from blood samples, and immune cells and functional cell-surface molecules were analyzed. We observed remarkable differences in the expression of HLAABC, MICA, CD40, and GPR43 in plasmacytoid DCs (pDCs) between the LcS-FM and CM groups, whereas no difference was found in CD86 or HLADR expression. The LcS-FM group exhibited higher CD40 expression in both conventional DCs (cDCs) and Mos, especially in type 2 conventional DCs (cDC2s) and classical monocytes (cMos); higher percentages of cMos, intermediate monocytes (iMos), and nonclassical monocytes; and higher numbers of cMos and iMos in PBMCs than the CM group. LcS ingestion increased the expression of HLAABC, MICA, CD40, and GPR43 in pDCs and CD40 in cDCs and Mos, particularly cDC2s and cMos. These results suggest that LcS modulates the function of MPCs that may lead to the regulation of immune effector functions in healthy adults.

Changes in immunological parameters by ageing in rural healthy Indian adults and their associations with sex and lifestyle.

Several factors including sex and lifestyle have been reported to contribute to the age-related alteration of immune functions. The study was undertaken to determine age-related differences in the proportion of peripheral blood mononuclear lymphocytes in the Indian population using blood samples from 67 healthy adults (33 females and 34 males) aged between 20 and 80 years old. In the linear regression analysis to estimate the relationship with age categories, there was a significant increase in the frequency of natural killer cells with ageing, while their cytolytic activity significantly declined. The frequency of CD4+ T cells increased with age, whereas that of CD8+ T cells decreased, resulting in the age-associated increase of the CD4/CD8 ratio. The subsets of B cells did not show any significant relationship with age. Although there were variations between the male and female subgroups in effect size of ageing, the trends were in the same direction in all the parameters. Reduced fat intake was associated with a lower frequency of CD4+ T cells, and higher serum cotinine level was associated with a higher CD4/CD8 ratio. The results indicate that cellular immunity in the Indian population is affected by ageing, while humoral immunity is less susceptible to ageing.

Probiotics: A Dietary Factor to Modulate the Gut Microbiome, Host Immune System, and Gut-Brain Interaction.

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.

Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage.

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.

Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice.

BACKGROUND: Obesity increases the risk for malignancies in various tissues including the stomach. Atrophic gastritis with precancerous lesions is an obesity-associated disease; however, the mechanisms that underlie the development of obesity-associated atrophic gastritis are unknown. Leptin is a hormone derived from stomach as well as adipose tissue and gastric leptin is involved in the development of gastric cancer. The aim of the current study is to investigate the involvement of leptin receptor signaling in the development of atrophic gastritis during diet-induced obesity. METHODS: Male C57BL/6, ob/ob and db/db mice were fed a high-fat diet (HFD) or a control diet (CD) from 1 week to 5 months. Pathological changes of the gastric mucosa and the expression of molecules associated with atrophic gastritis were evaluated in these mice. RESULTS: HFD feeding induced gastric mucosal hyperplasia with increased gastric leptin expression. Mucosal hyperplasia was accompanied by a higher frequency of Ki67-positive proliferating cells and atrophy of the gastric glands in the presence of inflammation, which increased following HFD feeding. Activation of ObR signaling-associated molecules such as ObR, STAT3, Akt, and ERK was detected in the gastric mucosa of mice fed the HFD for 1 week. The morphological alterations associated with gastric mucosal atrophy and the expression of Muc2 and Cdx2 resemble those associated with human intestinal metaplasia. In contrast to wild-type mice, leptin-deficient ob/ob mice and leptin receptor-mutated db/db mice did not show increased Cdx2 expression in response to HFD feeding. CONCLUSION: Together, these results suggest that activation of the leptin signaling pathway in the stomach is required to develop obesity-associated atrophic gastritis.

Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota.

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.

Effect of an oral administration of Lactobacillus casei strain Shirota on the natural killer activity of blood mononuclear cells in aged mice.

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.

Augmentation of cellular immunity and reduction of influenza virus titer in aged mice fed Lactobacillus casei strain Shirota.

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 XL.casei strain Shirota diet, potent induction of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), which play a very important role in excluding IFV, was evident in nasal lymphocytes. IFN-gamma and TNF-alpha 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.