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  • 1. Bielig, Harald
    et al.
    Dongre, Mitesh
    Zurek, Birte
    Wai, Sun N
    Kufer, Thomas A
    A role for quorum sensing in regulating innate immune responses mediated by Vibrio cholerae outer membrane vesicles (OMVs).2011In: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 2, no 5, p. 274-9Article in journal (Refereed)
    Abstract [en]

    Outer membrane vesicles (OMVs) are released from many Gram-negative bacteria. OMVs interact with and are taken up by human cells. We and others have now showed that OMVs contain peptidoglycan, which is sensed mainly by the pattern-recognition receptor NOD1 in the cytoplasm of host cells. Vibrio cholerae is clinically important as one of the causative agents of severe dehydrating diarrhea in humans. We showed that non-O1 non-O139 V. cholerae (NOVC) strains of V. cholera produce OMVs. Of note, we revealed that NOVC can evade NOD1-mediated immune surveillance by the quorum sensing machinery. Here we review these recent findings and discuss the relevance for our understanding of bacterial infections and innate immune responses.

  • 2. Birchenough, George
    et al.
    Schröder, Björn
    Bäckhed, Fredrik
    Hansson, Gunnar C
    Dietary destabilisation of the balance between the microbiota and the colonic mucus barrier.2019In: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 10, no 2, p. 246-250Article in journal (Refereed)
    Abstract [en]

    It has long been acknowledged that dietary fibres are important to maintain a healthy gut. Over the past decade, several studies have shown that loss of complex polysaccharides from the Western diet has resulted in alterations to our colonic microbiota. The concurrent increase in the incidence of inflammatory bowel disease in the Western world has driven us to explore the potential mechanistic link between diet, the microbiota and the host defence systems that normally prevent inflammation. Using mice fed a low fibre Western-style diet and robust live tissue analytical methods we have now provided evidence that this diet impairs the colonic inner mucus layer that normally separates bacteria from host cells. Western societies urgently need to develop their understanding of the molecular mechanisms of the diet-microbiota-mucus axis and its implications for inflammatory diseases.

  • 3.
    Murphy, Eileen F.
    et al.
    Alimentary Health Ltd., Cork, Ireland.
    Clarke, Siobhan F.
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    Marques, Tatiana M.
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    Hill, Colin
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    Stanton, Catherine
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    Ross, R. Paul
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    O'Doherty, Robert M.
    Department of Medicine, Division of Endocrinology and Metabolism and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh PA, USA.
    Shanahan, Fergus
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Department of Medicine, University College Cork, Cork, Ireland.
    Cotter, Paul D.
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    Antimicrobials: Strategies for targeting obesity and metabolic health?2013In: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 4, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with a number of serious health consequences, including type 2 diabetes, cardiovascular disease and a variety of cancers among others and has been repeatedly shown to be associated with a higher risk of mortality. The relatively recent discovery that the composition and metabolic activity of the gut microbiota may affect the risk of developing obesity and related disorders has led to an explosion of interest in this distinct research field. A corollary of these findings would suggest that modulation of gut microbial populations can have beneficial effects with respect to controlling obesity. In this addendum, we summarize our recent data, showing that therapeutic manipulation of the microbiota using different antimicrobial strategies may be a useful approach for the management of obesity and metabolic conditions. In addition, we will explore some of the mechanisms that may contribute to microbiota-induced susceptibility to obesity and metabolic diseases.

  • 4.
    Schröder, Björn O.
    et al.
    Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology; Stuttgart and University of Tübingen; Tübingen, Germany.
    Stange, Eduard F.
    Wehkamp, Jan
    Waking the wimp: Redox-modulation activates human beta-defensin 12011In: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 2, no 4, p. 262-266Article in journal (Refereed)
    Abstract [en]

    Antimicrobial peptides are key players of the innate immune system and form a primary barrier against infection by microorganisms. In humans, several classes of antimicrobial peptides are produced, including the defensins. These small, cationic peptides show broad spectrum antimicrobial activity against bacteria, some fungi and some viruses. Defensins are characterized by six conserved cysteine residues which are connected via three disulphide bridges. Depending on the pattern of connectivity, human defensins are either classified as α- or β-defensins. Human β-defensin 1 (hBD-1) is constitutively expressed by epithelia, but in comparison with other antimicrobial peptides the antimicrobial activity of hBD-1 was comparably low. We recently found that after reduction of hBD-1's three disulphide bonds its antimicrobial activity is strongly enhanced. Reduction can be either performed by a reducing environment, as it is present in parts of the human intestine, the oral cavity and other locations, or enzymatically by the thioredoxin-system, which is one of the major redox regulators. Reduced hBD-1 is able to kill Gram-positive anaerobic bacteria of the human normal flora as well as an opportunistic pathogenic fungus, whereas the oxidized peptide does not show activity against these microorganisms. Herein we provide additional data about reduced hBD-1 and discuss the biological context of our findings.

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