Evaluation of the cutaneous microbiome in psoriasis

Psoriasis, a highly prevalent disease of humans of unknown cause, is a chronic inflammatory disorder primarily involving skin, with distinctive clinical characteristics. With the newly developed tools that facilitate microbiome research, it now is possible to assess whether the cutaneous microbiome plays a role in the pathogenesis of this disorder. Preliminary data from our studies suggest that the cutaneous microbiome in psoriasis is complex and possibly different from normal. To deal with this complexity, we propose to examine the cutaneous microbiome in relation to psoriasis with explorations at several taxonomic and informatic levels. Our overall objective is to examine how changes in the normal cutaneous microbiome contributes to the pathogenesis of psoriasis. Since causality is complex and often difficult to prove, our overall hypothesis is that there are alterations in the cutaneous microbiome in areas of skin affected by psoriasis in comparison with the range observed in clinically unaffected areas, or in healthy persons. We also hypothesize that the characteristics of the microbiome may affect clinical responses to the immunomodulatory agents used to treat psoriasis. An alternative hypothesis is that effective treatment of psoriasis with systemic immunomodulatory agents will not substantially affect the disordered microbial ecosystem. Such observations would provide evidence for the roles of the microbiota in this disorder. Since an important consideration in microbiome research is the optimal level (e.g. phylum, genus, species, strain, gene) at which to examine a scientific question, and we are not yet certain what are the optimal levels for psoriasis, this also will be examined. Our studies of psoriasis should allow development of both approaches and tools that will have general utility for microbiome research. To test our hypothesis, we propose the following specific aims: 1. To understand the cutaneous microbiome species composition overlaying psoriatic lesions; 2. To investigate differences in metagenome content for psoriatic lesions compared to normal skin; 3. To identify differences in the transcriptional profiles of the microbiome and the host between normal skin and psoriatic lesions using high-throughput sequencing; and 4. To estimate the effects of systemic immunomodulatory therapy for psoriasis on microbiome composition. In total, these studies should help us understand the role of the microbiome in psoriasis pathogenesis

Role of the microbiome in human development.

The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration

Citrulline and intestinal fatty acid-binding protein as biomarkers for gastrointestinal dysfunction in the critically ill

Currently there is no reliable tool available to monitor gastrointestinal function in the critically ill. Biomarkers are therefore of great interest in this field as the lack of monitoring tools impedes any interventional studies. The potential biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) are the present focus. Targeted literature searches were undertaken for physiology and pathophysiology, sampling, measurement methods and clinical use of citrulline and I-FABP as biomarkers of intestinal function and injury. Physiology and pathophysiology, specific aspects of sampling and different laboratory assays are summarized and respective pitfalls outlined. Studies in animals and patients outside the ICU support the rationale for these biomarkers. At the same time, evidence in critically ill patients is not yet convincing, several specific aspects need to be clarified, and methodology and interpretation to be refined. We conclude that there are good physiological rationales for citrulline as a marker of enterocyte function and for I-FABP as a marker of intestinal injury, but further studies are needed to clarify whether and how they could be used in daily practice in caring for critically ill patients

Bacterial community structure and activity in different Cd-treated forest soils

In this study we compared indicators of Cd bioavailability (water extracts, Lakanen extracts, free ions) and ecotoxicity in forest soils with contrasting physico-chemical characteristics. Soil samples were treated with CdCl2 solutions (0, 0.1, 1, 10 and 100 mM) and incubated for 30 days. Microbial activity indexes (acid phosphatase, β-glucosidase, basal respiration) and changes in bacterial community structure using terminal restriction fragment length polymorphism (T-RFLP) fingerprinting were investigated. The Cd concentrations measured ranged from 1% to 37% of the total additions in water extracts, to higher levels in Lakanen extracts. Effects of Cd were observed at bioavailable concentrations exceeding United Nations/European Economic Commission UN/ECE guidelines for total Cd in the soil solution. Basal respiration was the most affected index, while enzymatic activities showed variable responses to the Cd treatments. We also noticed that soils with pH higher than 6.7 and clay content higher than 50% showed inhibition of basal respiration but no marked shift in bacterial community structure. Soils with lower pH (pH <5.8) with less clay content (<50%) showed in addition strong changes in the bacterial community structure. Our results provide evidence for the importance of relating the effects of Cd on the soil communities to soil properties and to bioavailabilit

Abdominal compliance: A bench-to-bedside review

Abdominal compliance is an important determinant and predictor of available workspace during laparoscopic surgery. Furthermore, critically ill patients with a reduced abdominal compliance are at an increased risk of developing intra-abdominal hypertension and abdominal compartment syndrome both of which are associated with high morbidity and mortality. Despite of this, abdominal compliance is a concept, which has been neglected in the past. Abdominal compliance is defined as a measure of the ease of abdominal expansion, expressed as a change in intra-abdominal volume per change in intra-abdominal pressure: abdominal compliance = delta intra-abdominal volume / delta intra-abdominal pressure. AC is a dynamic variable, dependent on base-line IAV and IAP as well as reshaping and stretching capacity. Whereas abdominal compliance itself can only rarely be measured, it always needs to be considered an important component of intra-abdominal pressure. Patients with decreased abdominal compliance are prone to fulminant development of abdominal compartment syndrome when concomitant risk factors for intra-abdominal hypertension are present. This review aims to clarify the pressure-volume relationship within the abdominal cavity. It highlights how different conditions and pathologies can affect abdominal compliance and which management strategies could be applied to avoid serious consequences of decreased abdominal compliance. We have pooled all available human data to calculate abdominal compliance values in patients acutely and chronically exposed to intra-abdominal hypertension and demonstrated an exponential abdominal pressure-volume relationship. Most importantly, patients with high level of intra-abdominal pressure have a reduced abdominal compliance. In these patients, only small reduction in intra-abdominal volume can significantly increase abdominal compliance and reduce intra-abdominal pressures. A greater knowledge on abdominal compliance may help in selecting a better surgical approach as well as reducing complications related to intra-abdominal hypertension

Fecal Viral Community Responses to High-Fat Diet in Mice.

Alterations in diet can have significant impact on the host, with high-fat diet (HFD) leading to obesity, diabetes, and inflammation of the gut. Although membership and abundances in gut bacterial communities are strongly influenced by diet, substantially less is known about how viral communities respond to dietary changes. Examining fecal contents of mice as the mice were transitioned from normal chow to HFD, we found significant changes in the relative abundances and the diversity in the gut of bacteria and their viruses. Alpha diversity of the bacterial community was significantly diminished in response to the diet change but did not change significantly in the viral community. However, the diet shift significantly impacted the beta diversity in both the bacterial and viral communities. There was a significant shift away from the relatively abundant Siphoviridae accompanied by increases in bacteriophages from the Microviridae family. The proportion of identified bacteriophage structural genes significantly decreased after the transition to HFD, with a conserved loss of integrase genes in all four experimental groups. In total, this study provides evidence for substantial changes in the intestinal virome disproportionate to bacterial changes, and with alterations in putative viral lifestyles related to chromosomal integration as a result of shift to HFD.IMPORTANCE Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities

Walls talk: Microbial biogeography of homes spanning urbanization.

Westernization has propelled changes in urbanization and architecture, altering our exposure to the outdoor environment from that experienced during most of human evolution. These changes might affect the developmental exposure of infants to bacteria, immune development, and human microbiome diversity. Contemporary urban humans spend most of their time indoors, and little is known about the microbes associated with different designs of the built environment and their interaction with the human immune system. This study addresses the associations between architectural design and the microbial biogeography of households across a gradient of urbanization in South America. Urbanization was associated with households' increased isolation from outdoor environments, with additional indoor space isolation by walls. Microbes from house walls and floors segregate by location, and urban indoor walls contain human bacterial markers of space use. Urbanized spaces uniquely increase the content of human-associated microbes-which could increase transmission of potential pathogens-and decrease exposure to the environmental microbes with which humans have coevolved