Dysbiosis is a hallmark of atopic dermatitis (AD). The composition of skin microbiome communities and the causality of dysbiosis in eczema have not been well established. The objective of this review is to describe the skin microbiome profile in AD and address whether there is a causal relationship between dysbiosis and AD. The protocol is registered in PROSPERO (CRD42016035813). We searched PubMed, Embase, Scopus and ClinicalTrials.gov for primary research studies applying culture-independent analysis on the microbiome on AD skin of humans and animal models. Two authors independently screened the full text of studies for eligibility and assessed risk of bias. Because of heterogeneity no quantitative synthesis was done. Of 5735 texts, 32 met the inclusion criteria (17 published: 11 human and six animal studies). The studies varied in quality and applied different methodology. The skin in AD had low bacterial diversity (lowest at dermatitis-involved sites) and three studies showed depletion of Malassezia spp. and high non-Malassezia fungal diversity. The relative abundance of Staphylococcus aureus and Staphylococcus epidermidis were elevated and other genera were reduced, including Propionibacterium. A mouse study indicated that dysbiosis is a driving factor in eczema pathogenesis. The data are not sufficiently robust for good characterization; however, dysbiosis in AD not only implicates Staphylococcus spp., but also microbes such as Propionibacterium and Malassezia. A causal role of dysbiosis in eczema in mice should encourage future studies to investigate if this also applies to humans. Other important aspects are temporal dynamics and the influence of methodology on microbiome data.
The human skin is colonized by a wide array of microorganisms playing a role in skin disorders. Studying the skin microbiome provides unique obstacles such as low microbial biomass. The objective of this study was to establish methodology for skin microbiome analyses, focusing on sampling technique and DNA extraction. Skin swabs and scrapes were collected from 9 healthy adult subjects, and DNA extracted using 12 commercial kits. All 165 samples were sequenced using the 16S rRNA gene. Comparing the populations captured by eSwabs and scrapes, 99.3% of sequences overlapped. Using eSwabs yielded higher consistency. The success rate of library preparation applying different DNA extraction kits ranged from 39% to 100%. Some kits had higher Shannon alpha-diversity. Metagenomic shotgun analyses were performed on a subset of samples (N = 12). These data indicate that a reduction of human DNA from 90% to 57% is feasible without lowering the success of 16S rRNA library preparation and without introducing taxonomic bias. Using swabs is a reliable technique to investigate the skin microbiome. DNA extraction methodology is crucial for success of sequencing and adds a substantial amount of variation in microbiome analyses. Reduction of host DNA is recommended for interventional studies applying metagenomics.
Background Skeletal metastatic disease excludes many cancer patients from participating in exercise and physical activity due to safety concerns. Empirical evidence from high-quality trials is warranted to guide clinicians and patients. Objective To evaluate the safety and potential benefits of high-impact aerobic exercise in patients with prostate cancer with skeletal metastases. Design Exploratory subgroup analysis of a pragmatic, multicentre, parallel randomised controlled trial. Setting The trial recruited 214 patients from five hospital urological departments in Denmark. Participants Patients with prostate cancer with skeletal metastases (n = 41). Intervention Six months of football training twice weekly at a local club or usual care. Both groups received brief information on physical activity recommendations at the time of randomisation. Main Outcome(s) and Measure(s) Safety, defined as falls, fractures and hospital admissions. Effects were evaluated on the primary outcome (prostate cancer-specific quality of life) and secondary outcomes (lean body mass, fat mass, hip and spine bone mineral density, and general physical and mental health). Results The original trial comprised 214 participants, 41 of whom had skeletal metastases at enrolment. Of these, 22 were allocated to football and 19 to usual care. The trial retention rate was 95% at 12 weeks and 88% at 6 months. Football participants attended 13 sessions on average at 12 weeks and 23 at 6 months. There were two falls, one in each group after 6 months, and no fractures. There were four unplanned hospital admissions in the study period, all four in the usual care group. Statistically significant between-group difference was observed in the primary outcome change in prostate cancer-specific quality of life at 12 weeks (7.6 points [95% CI 0.5 to 15.0]; P = 0.038). No statistical changes were found in the secondary outcomes. Conclusion The analysis showed that football training was safe in patients with skeletal metastatic prostate cancer and significantly improved quality of life. Larger analyses and/or trials are warranted to confirm the safety of exercise more broadly in cancer patients with skeletal metastatic disease. Trial Registration ClinicalTrials.gov, NCT02430792. Date of registration 30 April 2015
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