The microbiome in patients with atopic dermatitis.

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies

TGFβ/BMP immune signaling affects abundance and function of C. elegans gut commensals.

The gut microbiota contributes to host health and fitness, and imbalances in its composition are associated with pathology. However, what shapes microbiota composition is not clear, in particular the role of genetic factors. Previous work in Caenorhabditis elegans defined a characteristic worm gut microbiota significantly influenced by host genetics. The current work explores the role of central regulators of host immunity and stress resistance, employing qPCR and CFU counts to measure abundance of core microbiota taxa in mutants raised on synthetic communities of previously-isolated worm gut commensals. This revealed a bloom, specifically of Enterobacter species, in immune-compromised TGFβ/BMP mutants. Imaging of fluorescently labeled Enterobacter showed that TGFβ/BMP-exerted control operated primarily in the anterior gut and depended on multi-tissue contributions. Enterobacter commensals are common in the worm gut, contributing to infection resistance. However, disruption of TGFβ/BMP signaling turned a normally beneficial Enterobacter commensal to pathogenic. These results demonstrate specificity in gene-microbe interactions underlying gut microbial homeostasis and highlight the pathogenic potential of their disruption

Dysbiosis by neutralizing commensal mediated inhibition of pathobionts

Dysbiosis in the periodontal microbiota is associated with the development of periodontal diseases. Little is known about the initiation of dysbiosis. It was hypothesized that some commensal bacteria suppress the outgrowth of pathobionts by H2O2 production. However, serum and blood components released due to inflammation can neutralize this suppressive effect, leading to the initiation of dysbiosis. Agar plate, dual-species and multi-species ecology experiments showed that H2O2 production by commensal bacteria decreases pathobiont growth and colonization. Peroxidase and blood components neutralize this inhibitory effect primarily by an exogenous peroxidase activity without stimulating growth and biofilm formation of pathobionts directly. In multi-species environments, neutralization of H2O2 resulted in 2 to 3 log increases in pathobionts, a hallmark for dysbiosis. Our data show that in oral biofilms, commensal species suppress the amounts of pathobionts by H2O2 production. Inflammation can neutralize this effect and thereby initiates dysbiosis by allowing the outgrowth of pathobionts

In vitro increased respiratory activity of selected oral bacteria may explain competitive and collaborative interactions in the oral microbiome

Understanding the driving forces behind the shifts in the ecological balance of the oral microbiota will become essential for the future management and treatment of periodontitis. As the use of competitive approaches for modulating bacterial outgrowth is unexplored in the oral ecosystem, our study aimed to investigate both the associations among groups of functional compounds and the impact of individual substrates on selected members of the oral microbiome. We employed the Phenotype Microarray high-throughput technology to analyse the microbial cellular phenotypes of 15 oral bacteria. Multivariate statistical analysis was used to detect respiratory activity triggers and to assess similar metabolic activities. Carbon and nitrogen were relevant for the respiration of health-associated bacteria, explaining competitive interactions when grown in biofilms. Carbon, nitrogen, and peptides tended to decrease the respiratory activity of all pathobionts, but not significantly. None of the evaluated compounds significantly increased activity of pathobionts at both 24 and 48 h. Additionally, metabolite requirements of pathobionts were dissimilar, suggesting that collective modulation of their respiratory activity may be challenging. Flow cytometry indicated that the metabolic activity detected in the Biolog plates may not be a direct result of the number of bacterial cells. In addition, damage to the cell membrane may not influence overall respiratory activity. Our methodology confirmed previously reported competitive and collaborative interactions among bacterial groups, which could be used either as marker of health status or as targets for modulation of the oral environment

Mass mortalities in bivalve populations: A review of the edible cockle Cerastoderma edule (L.)

Mass mortalities in bivalve populations have long been of particular concern, especially when the species supports a commercial fishery or is of conservation interest. Here we consider the evidence of mass mortalities of the edible cockle, Cerastoderma edule (L.). Through the construction of a conceptual model eight potential factors (or groups of factors) which may cause mass mortalities are identified and reviewed. These include: food limitation; density; oxygen depletion and organic loadings; temperature and salinity; parasites, pathogens and commensals; toxicants and other persistent pollutants; predation, and changes in sediment, suspended solids, topography and bathymetry. The interplay between factors in recognized and discussed based on evidence mainly from the published literature relating to temperate edible cockle beds. Anecdotal evidence is also reported from a structured survey of site-specific evidence provided by fisheries managers in England and Wales. Case studies from the UK and Europe indicate that there is often no single, clear generic cause of mass mortalities in cockle populations. The importance of linked site-specific scientific investigations and laboratory-based experiments to fill the gaps in our current understanding of mass mortalities in bivalve species is highlighted as necessary to take account of both local extrinsic and intrinsic factors

How gut sampling and microbial invasiveness/noninvasiveness provides mucosal immunity with a nonmolecular pattern means to distinguish commensals from pathogens: A review

Mucosal immunity distinguishes not only different microbial antigens but also separates those of pathogens from those of commensals. How this is done is unknown. The present view is that the pathogen/commensal determination of antigens depends upon as yet to be discovered molecular patterns. Here I review the biological feasibility that it also involves the detection of the invasive differences in their motility towards the gut wall when they are sampled by differently biased methods. 

By their nature, pathogens and commensals have different motility – invasive and noninvasive – in regard to the epithelium. The immune system is in a position to detect such motility differences. This biological opportunity arises since different microbe sampling methods can “catch” different groups of microbes depending upon how their motility interacts with the epithelium. A biological method biased to sample those with invasive motility—pathogens—could be achieved by ‘honey pot traps’ that preferentially (but not exclusively) sample microbes that have a taxis to breaches in the epithelium. A biological method biased to sample those that are noninvasive—commensals—could be done by capturing microbes that are passively and stably residing in the biofilm “offshore” of the epithelium. Such differential sampling strategies would seem to relate to those carried out respectively by (i) M-cells (working with subepithelial dome dendritic cells), and (ii) sub- and intraepithelial dendritic cells.

The interactions of antigen presentation can be arranged so that the immune system links antigens from biased microbial sampling with pathogenic or commensal appropriate immune responses. Such immune classification could feasibly occur biologically through a winner-take-all competition between inhibiting and activating antigen presentation. Winner-takes-all types of processing classification are already known to underlie the biologically interactions between neurons that classify sensory inputs making it also plausible that they are exploited by the immune system. In pathogen identification, M-cell antigens would be activating and biofilm antigens inhibitory, and vise versa for commensal identification. This winner-take-all competition between antigen presentation would act to amplify small statistical biases in the two samples linked to invasiveness/noninvasiveness into a reliable pathogen/commensal distinction. This process would both complement, and acts as independent guarantor, upon the alternative pathogenicity/commensality recognition provided by molecular pattern recognition. 

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A degenerate PCR-based strategy as a means of identifying homologues of aminoglycoside and ß-lactam resistance genes in the gut microbiota

peer-reviewedBackground: The potential for the human gut microbiota to serve as a reservoir for antibiotic resistance genes has been the subject of recent discussion. However, this has yet to be investigated using a rapid PCR-based approach. In light of this, here we aim to determine if degenerate PCR primers can detect aminoglycoside and β-lactam resistance genes in the gut microbiota of healthy adults, without the need for an initial culture-based screen for resistant isolates. In doing so, we would determine if the gut microbiota of healthy adults, lacking recent antibiotic exposure, is a reservoir for resistance genes. Results: The strategy employed resulted in the identification of numerous aminoglycoside (acetylation, adenylation and phosphorylation) and β-lactam (including bla OXA, bla TEM, bla SHV and bla CTX-M) resistance gene homologues. On the basis of homology, it would appear that these genes originated from different bacterial taxa, with members of the Enterobacteriaceae being a particularly rich source. The results demonstrate that, even in the absence of recent antibiotic exposure, the human gut microbiota is a considerable reservoir for antibiotic resistance genes. Conclusions: This study has demonstrated that the gut can be a significant source of aminoglycoside and β-lactam resistance genes, even in the absence of recent antibiotic exposure. The results also demonstrate that PCR-based approaches can be successfully applied to detect antibiotic resistance genes in the human gut microbiota, without the need to isolate resistant strains. This approach could also be used to rapidly screen other complex environments for target genes.Fiona Fouhy is in receipt of an Irish Research Council EMBARK scholarship and is a Teagasc Walsh fellow. Research in the PDC laboratory is also supported by the Irish Government under the National Development Plan through the Science Foundation Ireland Investigator award 11/PI/113