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Chung H.,Harvard University | Pamp S.J.,Stanford University | Hill J.A.,Harvard University | Surana N.K.,Harvard University | And 11 more authors.
Cell | Year: 2012

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4+ and CD8+ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression - all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system. PaperClip: © 2012 Elsevier Inc.

Yurkovetskiy L.,University of Chicago | Burrows M.,University of Chicago | Khan A.,University of Chicago | Graham L.,University of Chicago | And 6 more authors.
Immunity | Year: 2013

Gender bias and the role of sex hormones in autoimmune diseases are well established. In specific pathogen-free nonobese diabetic (NOD) mice, females have 1.3-4.4 times higher incidence of type 1 diabetes (T1D). Germ-free (GF) mice lost the gender bias (female-to-male ratio 1.1-1.2). Gut microbiota differed in males and females, a trend reversed by male castration, confirming that androgens influence gut microbiota. Colonization of GF NOD mice with defined microbiota revealed that some, but not all, lineages overrepresented in male mice supported a gender bias in T1D. Although protection of males did not correlate with blood androgen concentration, hormone-supported expansion of selected microbial lineages may work as a positive-feedback mechanism contributing to the sexual dimorphism of autoimmune diseases. Gene-expression analysis suggested pathways involved in protection of males from T1D by microbiota. Our results favor a two-signal model of gender bias, in which hormones and microbes together trigger protective pathways. © 2013 Elsevier Inc.

Nanno M.,Yakult Central Institute for Microbiological Research
International journal of immunopathology and pharmacology | Year: 2011

Probiotics have been defined as live bacteria beneficial to the host when administered in adequate amounts. To evaluate the effect of probiotics on the prevention of carcinogenesis, Lactobacillus casei Shirota (LcS) was given to the patients who had undergone the resection of superficial bladder cancer, and administration of LcS significantly reduced the recurrence rate of bladder cancer. When LcS was given to the patients whose colonic polyps were surgically removed, the recurrence of colorectal cancer with moderate or severe atypia was suppressed. To assess the putative actions of LcS on innate immune responses, we examined the effect of LcS on natural killer (NK) cell activity in humans. Daily ingestion of fermented milk containing LcS restored NK cell activity in healthy subjects with low NK cell activity as well as human T lymphotropic virus (HTLV)-1-associated myelopathy patients. When peripheral blood mononuclear cells from healthy humans were cultured in the presence of heat-killed LcS, NK cell activity was augmented, which were partly mediated by monocyte-derived interleukin (IL)-12. These findings suggest that LcS may help the reinforcement of our defense system against cancer by modulating innate immune functions.

Tanigawa K.,Yakult Central Institute for Microbiological Research | Kawabata H.,Meiji University | Watanabe K.,Yakult Central Institute for Microbiological Research
Applied and Environmental Microbiology | Year: 2010

Currently, the genus Lactococcus is classified into six species: Lactococcus chungangensis, L. garvieae, L. lactis, L. piscium, L. plantarum, and L. raffinolactis. Among these six species, L. lactis is especially important because of its use in the manufacture of probiotic dairy products. L. lactis consists of three subspecies: L. lactis subsp. cremoris, L. lactis subsp. hordniae, and L. lactis subsp. lactis. However, these subspecies have not yet been reliably discriminated. To date, mainly phenotypic identification has been used, with a few genotypic identifications. We discriminated species or subspecies in the genus Lactococcus not only by proteomics identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) but also by phenotypic and genotypic identification. The proteomics identification using differences in the mass spectra of ribosomal proteins was nearly identical to that by genotypic identification (i.e., by analyses of 16S rRNA and recA gene sequences and amplified fragment length polymorphism). The three ribosomal subunits 30S/L31, 50S/L31, and 50S/L35 were the best markers for discriminating L. lactis subsp. cremoris from L. lactis subsp. lactis. Proteomics identification using MALDI-TOF MS was therefore a powerful method for discriminating and identifying these bacteria. In addition, this method was faster and more reliable than others that we examined. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Deguchi Y.,Yakult Central Institute for Microbiological Research | Miyazaki K.,Yakult Central Institute for Microbiological Research
Nutrition and Metabolism | Year: 2010

Psidium guajava Linn. (guava) is used not only as food but also as folk medicine in subtropical areas around the world because of its pharmacologic activities. In particular, the leaf extract of guava has traditionally been used for the treatment of diabetes in East Asia and other countries. Moreover, the anti-hyperglycemic activity of the extract has been reported in some animal models. However, little is known regarding the therapeutic activity of the extract in human clinical trials as well as its underlying therapeutic mechanisms and safety. In Japan, Guava Leaf Tea (Bansoureicha®, Yakult Honsha, Tokyo, Japan) containing the aqueous leaf extract from guava has been approved as one of the Foods for Specified Health Uses and is now commercially available. This review describes the active component of the aqueous guava leaf extract and its inhibition of alpha-glucosidase enzymes in vitro, safety of the extract and Guava Leaf Tea, reduction of postprandial blood glucose elevation, and improvement of hyperglycemia, hyperinsulinemia, hypoadiponectinemia, hypertriglycemia and hypercholesterolemia in murine models and several clinical trials. It is suggested that the chronic suppression of postprandial blood glucose elevation is important in preventing type 2 diabetes mellitus, and that Guava Leaf Tea is considered useful as an alimentotherapy for chronic treatment. © 2010 Deguchi and Miyazaki; licensee BioMed Central Ltd.

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