Immune Function of Probiotic Bacterial DNA and Their Advanced Application to Food Immunology

The toll-like receptor (TLR) family plays an important role in host defense through recognizing bacterial pathogen-associated molecular patterns. The induction of the host defense system begins with the recognition of pathogens. To date, 13 types of TLR, which function as a kind of pathogen sensor, have been identified. Our recent research on the physiological function of food products has investigated the immunoregulatory effects of probiotic lactic acid bacteria (LAB) via TLR. On the basis of our study, efforts have been made to develop a molecular immunoassay system for probiotic LAB and find novel immunostimulatory DNA sequences from probiotics and high potential immunobiotic LAB strains via TLR9 signaling. These findings may provide important clues at the molecular level on TLR signal transduction pathways and recognition mechanisms for the ligands. In addition to identifying immunoregulatory factor immunogenics from LAB, a better understanding of intestinal immune regulation through cytokine networks holds out promise for basic food immunology research and the development of immunobiotic foods/feeds to prevent specific diseases.OtherShinshu University International Symposium 2010 : Sustainable Agriculture and Environment : Asian Networks II 　信州大学国際シンポジウム2010 : 持続的農業と環境 : アジアネットワークII ― アジアネットワークの発展をめざして―. 信州大学農学部, 2010, 93-97conference pape

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic inflammatory diseases characterized by dysregulated immune responses of the gastrointestinal tract. In recent years, the incidence of IBDs has increased in developed nations, but their prophylaxis/treatment is not yet established. Site-directed delivery of molecules showing anti-inflammatory properties using genetically modified (gm) probiotics shows promise as a new strategy for the prevention and treatment of IBD. Advantages of gm-probiotics include 1) the ability to use bacteria as a delivery vehicle, enabling safe and long-term use by humans, 2) decreased risks of side effects, and 3) reduced costs. The intestinal delivery of anti-inflammatory proteins such as cytokines and enzymes using Lactococcus lactis has been shown to regulate host intestinal homeostasis depending on the delivered protein-specific machinery. Additionally, clinical experience using interleukin 10-secreting Lactococcus lactis has been shown to be safe and to facilitate biological containment in IBD therapy. On the other hand, some pre-clinical studies have demonstrated that gm-strains of immunobiotics (probiotics strains able to beneficially regulate the mucosal immunity) provide beneficial effects on intestinal inflammation as a result of the synergy between the immunoregulatory effects of the bacterium itself and the anti-inflammatory effects of the delivered recombinant proteins. In this review, we discuss the rapid progression in the development of strategies for the prophylaxis and treatment of IBD using gm-probiotics that exhibit immune regulation effects (gm-immunobiotics). In particular, we discuss the type of strains used as delivery agents.ArticleFrontiers in Immunology. 8:22 (2017)journal articl

Development of a New Treatment Modality for Lung Diseases That Uses Innovative Fine Droplet Drying (fdd) Technology Offering Inhalable Nano/microparticles-incorporated Therapeutic Agents.

ArticleImpact. 2019(3): 56-58. (2019)journal articl

Anti-allergic effects of a mixture of Saccharomyces cerevisiae and its specific goat's milk immunoglobulin G rich fraction on ovalbumin sensitized BALB/c mice

In this study, we investigated the effects of oral ingestion of Saccharomyces (S.) cerevisiae and its specific immunoglobulin (Ig) G-rich fraction, prepared from goat's milk, on immune function in an allergic rhinitis mouse model, ovalbumin (OVA)-sensitized BALB/c mice. Sneezing activity in mice that were administered a feed containing a mixture of S. cerevisiae and its specific goat's milk IgG-rich fraction (mixture group) was significantly lower than that in mice administered the mixture-free feed (control group) at age 11 and 12 weeks, although the activity in mice that were given a feed containing S. cerevisiae (yeast group) was similar to that of the control group. We found that the ratio of spleen interferon-gamma(+)CD4(+) cell/interleukin (IL)-4(+)CD4(+) cell was higher in the mixture and yeast groups than the control group. The number of spleen CD80(+)CD11b(+) cells was significantly lower in the mixture and yeast groups than the control group. In contrast, the numbers of spleen CD122(+)CD8 alpha(+) and IL-10(+)CD4(+) cells were significantly higher in the mixture group than the control and yeast groups while the numbers of IgE(+)B220(+) and Fc epsilon RI alpha(+)CD117(+) cells were significantly lower in the mixture group. These results suggested that the mixture of S. cerevisiae and its specific goat's milk IgG-rich fraction reduced OVA-induced allergic symptoms in BALB/c mice via the induction of suppressor T cells and the reduction of Ig E-producing cells and high affinity IgE receptor-positive mast cells rather than the adjustment of the Th1/Th2 balance.ArticleMILCHWISSENSCHAFT-MILK SCIENCE INTERNATIONAL. 66(1): 7-10(2011)journal articl

Effect of Probiotics/Prebiotics on Cattle Health and Productivity

Probiotics/prebiotics have the ability to modulate the balance and activities of the gastrointestinal (GI) microbiota, and are, thus, considered beneficial to the host animal and have been used as functional foods. Numerous factors, such as dietary and management constraints, have been shown to markedly affect the structure and activities of gut microbial communities in livestock animals. Previous studies reported the potential of probiotics and prebiotics in animal nutrition; however, their efficacies often vary and are inconsistent, possibly, in part, because the dynamics of the GI community have not been taken into consideration. Under stressed conditions, direct-fed microbials may be used to reduce the risk or severity of scours caused by disruption of the normal intestinal environment. The observable benefits of prebiotics may also be minimal in generally healthy calves, in which the microbial community is relatively stable. However, probiotic yeast strains have been administered with the aim of improving rumen fermentation efficiency by modulating microbial fermentation pathways. This review mainly focused on the benefits of probiotics/prebiotics on the GI microbial ecosystem in ruminants, which is deeply involved in nutrition and health for the animal.ArticleMICROBES AND ENVIRONMENTS. 30(2):126-132 (2015)journal articl

Oral administration of a fruiting body extract of Boletopsis leucomelas enhances intestinal IgA production in LPS-challenged mice

The present study showed that a hot water extract of the fruiting body of the edible mushroom Boletopsis leucomelas, known as 'Kurokawa' Japanese, strongly stimulated IgA-production in mouse spleen cells in our screening experiment. The in vivo study was also conducted with the objective of enhancing adaptive immune response by oral administration of the hot water extract of B. leucomelas (BLE) in lipopolysaccharide (LPS)-challenged mice. The mice were fed a standard diet with or without 0.16% BLE. The mice were also orally administered sodium phosphate buffer or LPS weekly at days 7, 14 and 21. Results indicated that LPS-specific serum IgG, IgM and IgA were increased in the BLE diet group compared to the standard diet group. Interestingly, intestinal total IgA and LPS-specific IgA were significantly increased in the BLE diet group. Moreover, the <1000 Da, 5000-10,000 Da phenol sulphate-positive molecules from BLE showed significant IgA-producing activity.ArticleFOOD AND AGRICULTURAL IMMUNOLOGY. 25(4):510-522 (2014)journal articl

Extra-embryonic endoderm cells derived from ES cells induced by GATA Factors acquire the character of XEN cells

<p>Abstract</p> <p>Background</p> <p>Three types of cell lines have been established from mouse blastocysts: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extra-embryonic endoderm (XEN) cells, which have the potential to differentiate into their respective cognate lineages. ES cells can differentiate <it>in vitro </it>not only into somatic cell lineages but into extra-embryonic lineages, including trophectoderm and extra-embryonic endoderm (ExEn) as well. TS cells can be established from ES cells by the artificial repression of <it>Oct3/4 </it>or the upregulation of <it>Cdx2 </it>in the presence of FGF4 on feeder cells. The relationship between these embryo-derived XEN cells and ES cell-derived ExEn cell lines remains unclear, although we have previously reported that overexpression of <it>Gata4 </it>or <it>Gata6 </it>induces differentiation of mouse ES cells into extra-embryonic endoderm in vitro.</p> <p>Results</p> <p>A system in which GATA factors were conditionally activated revealed that the cells continue to proliferate while expressing a set of extra-embryonic endoderm markers, and, following injection into blastocysts, contribute only to the extra-embryonic endoderm lineage <it>in vivo</it>. Although the <it>in vivo </it>contribution is limited to cells of parietal endoderm lineage, Gata-induced extra-embryonic endoderm cells (gExEn) can be induced to differentiate into visceral endoderm-like cells <it>in vitro </it>by repression of <it>Gata6</it>. During early passage, the propagation of gExEn cells is dependent on the expression of the <it>Gata6 </it>transgene. These cells, however, lose this dependency following establishment of endogenous <it>Gata6 </it>expression.</p> <p>Conclusion</p> <p>We show here that Gata-induced extra-embryonic endoderm cells derived from ES cells mimic the character of XEN cells. These findings indicate that Gata transcription factors are sufficient for the derivation and propagation of XEN-like extra-embryonic endoderm cells from ES cells.</p

Sox7 is dispensable for primitive endoderm differentiation from mouse ES cells

Abstract Background Primitive endoderm is a cell lineage segregated from the epiblast in the blastocyst and gives rise to parietal and visceral endoderm. Sox7 is a member of the SoxF gene family that is specifically expressed in primitive endoderm in the late blastocyst, although its function in this cell lineage remains unclear. Results Here we characterize the function of Sox7 in primitive endoderm differentiation using mouse embryonic stem (ES) cells as a model system. We show that ectopic expression of Sox7 in ES cells has a marginal effect on triggering differentiation into primitive endoderm-like cells. We also show that targeted disruption of Sox7 in ES cells does not affect differentiation into primitive endoderm cells in embryoid body formation as well as by forced expression of Gata6. Conclusions These data indicate that Sox7 function is supplementary and not essential for this differentiation from ES cells

Sox7 is dispensable for primitive endoderm differentiation from mouse ES cells.

BACKGROUND: Primitive endoderm is a cell lineage segregated from the epiblast in the blastocyst and gives rise to parietal and visceral endoderm. Sox7 is a member of the SoxF gene family that is specifically expressed in primitive endoderm in the late blastocyst, although its function in this cell lineage remains unclear. RESULTS: Here we characterize the function of Sox7 in primitive endoderm differentiation using mouse embryonic stem (ES) cells as a model system. We show that ectopic expression of Sox7 in ES cells has a marginal effect on triggering differentiation into primitive endoderm-like cells. We also show that targeted disruption of Sox7 in ES cells does not affect differentiation into primitive endoderm cells in embryoid body formation as well as by forced expression of Gata6. CONCLUSIONS: These data indicate that Sox7 function is supplementary and not essential for this differentiation from ES cells