scholarly journals 2296

2017 ◽  
Vol 1 (S1) ◽  
pp. 15-15
Author(s):  
Di Yan ◽  
Hsin-Wen Chang ◽  
Rasnik Singh ◽  
Kevin Lai ◽  
Kristina Lee ◽  
...  
Keyword(s):  
16S Rrna ◽  
Inflammatory Diseases ◽  
Community Diversity ◽  
Psoriatic Skin ◽  
Skin Microbiome ◽  
Healthy Controls ◽  
General Role ◽  
Functional Roles ◽  
Microbiome Composition ◽  
Α Diversity

OBJECTIVES/SPECIFIC AIMS: Psoriasis is one of the most common inflammatory diseases of the skin, affecting about 2%–3% of the US population. Despite its high prevalence, its pathogenesis remains poorly understood. The ability of the microbiome to modify host immunity and metabolism suggests that it may contribute to the development of psoriasis and its cardiometabolic comorbidities. This study aims to characterize the psoriatic skin microbiome and understand the functional role that these bacteria may play. METHODS/STUDY POPULATION: 16s rRNA sequencing of site-matched skin swabs from 8 psoriasis patients and 8 healthy controls was used to identify bacteria and determine their relative abundance and microbial community diversity in the sample. PICRUSt was used to infer the functional roles of the bacteria from 16s rRNA amplicon data. RESULTS/ANTICIPATED RESULTS: Lesional psoriasis skin had lower α diversity (p=0.04), less Actinobacteria (p=0.0001), but higher Firmicutes (p=0.009) compared with controls. At the genus level, lesional skin had more Alloiococcus (p=0.01) and Aerococcus (p=0.01) and demonstrated a trend towards lower Propionibacterium (p=0.08) and higher Gallicola (p=0.09) compared to controls. Interestingly, Alloiococcus (p=0.003) and Gallicola (p=0.04) were also higher in nonlesional skin compared with controls. Furthermore, lesional and nonlesional skin shared an increased abundance of Acinetobacter sp., Staphylococcus pettenkoferi, and Streptococcus sp., relative to controls. Lesional and nonlesional psoriasis skin did not differ significantly in microbiome composition. Predictive functional analysis revealed that both the healthy and psoriatic skin microbiome were enriched with bacteria capable of amino acid and carbohydrate metabolism suggest these functions might have a general role in host-microbe interaction. DISCUSSION/SIGNIFICANCE OF IMPACT: These data reveal intriguing differences in the cutaneous microbiome of psoriatic individuals and healthy controls and suggest that bacterial metabolism may play an important role in host-microbe interaction.

scholarly journals Skin Microbiome in Patients with Hand Eczema and Healthy Controls: A Three-week Prospective Study

2021 ◽  
Author(s):  
Line Brok Nørreslet ◽  
Berit Lilje ◽  
Anna Cäcilia Ingham ◽  
Sofie Marie Edslev ◽  
Maja-Lisa Clausen ◽  
...  
Keyword(s):  
Prospective Study ◽  
Disease Severity ◽  
Amplicon Sequencing ◽  
Hand Eczema ◽  
Skin Microbiome ◽  
Healthy Controls ◽  
16S Rrna Amplicon Sequencing ◽  
Chronic Hand Eczema ◽  
Α Diversity ◽  
Underlying Mechanisms

The pathogenesis of chronic hand eczema remains unclear. Insights into the skin microbiome in hand eczema and its potential relevance to disease severity may help to elucidate the underlying mechanisms of hand eczema. The aim of this study was to characterize the microbiome in patients with hand eczema and healthy controls. A 5-visit prospective study was conducted over a period of 3 weeks. At each visit, bacterial swabs were taken from the hands of patients with hand eczema and controls. The microbiome was examined using DNA extraction and 16S rRNA amplicon sequencing (V3–V4 regions). Fifty patients with hand eczema and 50 controls were included (follow-up rate=100%). The baseline bacterial α-diversity was reduced on the hands of patients with hand eczema compared with controls (effect size=–0.31; 95% confidence interval (95% CI) –0.50; –0.11; p = 0.003). The dysbiosis on the patients’ hands was stable over the study period, was associated with disease severity, and was characterized by reduced bacterial diversity and different bacterial community compositions.

scholarly journals Interactions of host defense and hyper-keratinization in psoriasis

2021 ◽  
Author(s):  
Jingwen Deng ◽  
Emmerik Leijten ◽  
Michel Olde Nordkamp ◽  
Hartgring Sarita ◽  
Weiyang Tao ◽  
...  
Keyword(s):  
Host Defense ◽  
Gene Networks ◽  
Neutrophil Activation ◽  
Psoriatic Skin ◽  
Skin Microbiome ◽  
Core Network ◽  
Local Skin ◽  
Microbiome Composition ◽  
Core Set ◽  
Lesion Skin

Objectives: To understand the crosstalk between the host and microbiota in psoriatic skin, using a systems biology approach based on transcriptomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions, and the associations between the host defense and microbiota dynamic. Results: We found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using co-expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a "core" set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the "core network" of genes. Conclusions: We identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition.

scholarly journals The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Veda D. Khadka ◽  
Felix M. Key ◽  
Carolina Romo-González ◽  
Adrián Martínez-Gayosso ◽  
Blanca L. Campos-Cabrera ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
16S Rrna ◽  
Standard Treatment ◽  
Therapeutic Option ◽  
Alpha Diversity ◽  
Healthy Children ◽  
Skin Microbiome ◽  
Healthy Controls ◽  
Double Blinded ◽  
To Receive

BackgroundAtopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics.ObjectivesTo characterize changes in the skin microbiome during treatment for AD.MethodsThe skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification.ResultsWe included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment.ConclusionsThere are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

scholarly journals Skin Barrier Function in Psoriasis and Atopic Dermatitis: Transepidermal Water Loss and Temperature as Useful Tools to Assess Disease Severity

2021 ◽  
Vol 10 (2) ◽  
pp. 359 ◽  
Author(s):  
Trinidad Montero-Vilchez ◽  
María-Victoria Segura-Fernández-Nogueras ◽  
Isabel Pérez-Rodríguez ◽  
Miguel Soler-Gongora ◽  
Antonio Martinez-Lopez ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Water Loss ◽  
Barrier Function ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Diagnostic Tools ◽  
Psoriatic Skin ◽  
Skin Barrier Function ◽  
Healthy Controls

Multiple diagnostic tools are used to evaluate psoriasis and atopic dermatitis (AD) severity, but most of them are based on subjective components. Transepidermal water loss (TEWL) and temperature are skin barrier function parameters that can be objectively measured and could help clinicians to evaluate disease severity accurately. Thus, the aims of this study are: (1) to compare skin barrier function between healthy skin, psoriatic skin and AD skin; and (2) to assess if skin barrier function parameters could predict disease severity. A cross-sectional study was designed, and epidermal barrier function parameters were measured. The study included 314 participants: 157 healthy individuals, 92 psoriatic patients, and 65 atopic dermatitis patients. TEWL was significantly higher, while stratum corneum hydration (SCH) (8.71 vs. 38.43 vs. 44.39 Arbitrary Units (AU)) was lower at psoriatic plaques than at uninvolved psoriatic skin and healthy controls. Patients with both TEWL > 13.85 g·m−2h−1 and temperature > 30.85 °C presented a moderate/severe psoriasis (psoriasis area severity index (PASI) ≥ 7), with a specificity of 76.3%. TEWL (28.68 vs. 13.15 vs. 11.60 g·m−2 h−1) and temperature were significantly higher, while SCH (25.20 vs. 40.95 vs. 50.73 AU) was lower at AD eczematous lesions than uninvolved AD skin and healthy controls. Patients with a temperature > 31.75 °C presented a moderate/severe AD (SCORing Atopic Dermatitis (SCORAD) ≥ 37) with a sensitivity of 81.8%. In conclusion, temperature and TEWL values may help clinicians to determine disease severity and select patients who need intensive treatment.

scholarly journals Comparison of Respiratory Microbiome Disruption Indices to Predict VAP and VAE risk at LTACH Admission

2020 ◽  
Vol 41 (S1) ◽  
pp. s179-s180
Author(s):  
Erik Clarke ◽  
Kathleen None Chiotos ◽  
James Harrigan ◽  
Ebbing Lautenbach ◽  
Emily Reesey ◽  
...  
Keyword(s):  
Critical Illness ◽  
Bacterial Community ◽  
16S Rrna ◽  
Respiratory Tract ◽  
Predictive Performance ◽  
Community Diversity ◽  
Rrna Gene ◽  
Sequence Variant ◽  
Antibiotic Exposure ◽  
Shannon Diversity

Background: Healthcare exposure results in significant microbiome disruption, particularly in the setting of critical illness, which may contribute to risk for healthcare-associated infections (HAIs). Patients admitted to long-term acute-care hospitals (LTACHs) have extensive prior healthcare exposure and critical illness; significant microbiome disruption has been previously documented among LTACH patients. We compared the predictive value of 3 respiratory tract microbiome disruption indices—bacterial community diversity, dominance, and absolute abundance—as they relate to risk for ventilator-associated pneumonia (VAP) and adverse ventilator-associated events (VAE), which commonly complicate LTACH care. Methods: We enrolled 83 subjects on admission to an academic LTACH for ventilator weaning and performed longitudinal sampling of endotracheal aspirates, followed by 16S rRNA gene sequencing (Illumina HiSeq), bacterial community profiling (QIIME2) for diversity, and 16S rRNA quantitative PCR (qPCR) for total bacterial abundance. Statistical analyses were performed with R and Stan software. Mixed-effects models were fit to relate the admission MDIs to subsequent clinically diagnosed VAP and VAE. Results: Of the 83 patients, 19 had been diagnosed with pneumonia during the 14 days prior to LTACH admission (ie, “recent past VAP”); 23 additional patients were receiving antibiotics consistent with empiric VAP therapy within 48 hours of admission (ie, “empiric VAP therapy”); and 41 patients had no evidence of VAP at admission (ie, “no suspected VAP”). We detected no statistically significant differences in admission Shannon diversity, maximum amplicon sequence variant (ASV)–level proportional abundance, or 16S qPCR across the variables of interest. In isolation, all 3 admission microbiome disruption indices showed poor predictive performance, though Shannon diversity performed better than maximum ASV abundance. Predictive models that combined (1) bacterial diversity or abundance with (2) recent prior VAP diagnosis and (3) concurrent antibiotic exposure best predicted 14-day VAP (type S error < 0.05) and 30-day VAP (type S error < 0.003). In this cohort, VAE risk was paradoxically associated with higher admission Shannon diversity and lower admission maximum ASV abundance. Conclusions: In isolation, respiratory tract microbiome disruption indices obtained at LTACH admission showed poor predictive performance for subsequent VAP and VAE. But diversity and abundance models incorporating recent VAP history and admission antibiotic exposure performed well predicting 14-day and 30-day VAP.Disclosures: NoneFunding: None

scholarly journals Pre-digest of unprotected DNA by Benzonase improves the representation of living skin bacteria and efficiently depletes host DNA

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Yacine Amar ◽  
Ilias Lagkouvardos ◽  
Rafaela L. Silva ◽  
Oluwaseun Ayodeji Ishola ◽  
Bärbel U. Foesel ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Bacterial Load ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Skin Microbiome ◽  
Mock Community ◽  
Skin Bacteria ◽  
Α Diversity ◽  
Microbial Turnover ◽  
Microbial Dna

Abstract Background The identification of microbiota based on next-generation sequencing (NGS) of extracted DNA has drastically improved our understanding of the role of microbial communities in health and disease. However, DNA-based microbiome analysis cannot per se differentiate between living and dead microorganisms. In environments such as the skin, host defense mechanisms including antimicrobial peptides and low cutaneous pH result in a high microbial turnover, likely resulting in high numbers of dead cells present and releasing substantial amounts of microbial DNA. NGS analyses may thus lead to inaccurate estimations of microbiome structures and consequently functional capacities. Results We investigated in this study the feasibility of a Benzonase-based approach (BDA) to pre-digest unprotected DNA, i.e., of dead microbial cells, as a method to overcome these limitations, thus offering a more accurate assessment of the living microbiome. A skin mock community as well as skin microbiome samples were analyzed using 16S rRNA gene sequencing and metagenomics sequencing after DNA extraction with and without a Benzonase digest to assess bacterial diversity patterns. The BDA method resulted in less reads from dead bacteria both in the skin mock community and skin swabs spiked with either heat-inactivated bacteria or bacterial-free DNA. This approach also efficiently depleted host DNA reads in samples with high human-to-microbial DNA ratios, with no obvious impact on the microbiome profile. We further observed that low biomass samples generate an α-diversity bias when the bacterial load is lower than 105 CFU and that Benzonase digest is not sufficient to overcome this bias. Conclusions The BDA approach enables both a better assessment of the living microbiota and depletion of host DNA reads. Graphical abstract

scholarly journals Effects of Transanal Irrigation on Gut Microbiota in Pediatric Patients with Spina Bifida

2021 ◽  
Vol 10 (2) ◽  
pp. 224
Author(s):  
Akira Furuta ◽  
Yasuyuki Suzuki ◽  
Ryosuke Takahashi ◽  
Birte Petersen Jakobsen ◽  
Takahiro Kimura ◽  
...  
Keyword(s):  
Spina Bifida ◽  
16S Rrna ◽  
Gut Microbiota ◽  
Pediatric Patients ◽  
Host Immune System ◽  
Healthy Controls ◽  
Transanal Irrigation ◽  
Rrna Sequencing ◽  
Before And After ◽  
Neurogenic Bowel

Recent studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in constipated patients. The aim of this study was to investigate the changes in gut microbiota after transanal irrigation (TAI) in patients with spina bifida (SB). A questionnaire on neurogenic bowel disfunction (NBD), Bristol scale, and gut microbiota using 16S rRNA sequencing were completed in 16 SB patients and 10 healthy controls aged 6–17 years. Then, 11 of 16 SB patients with moderate to severe NBD scores received TAI for 3 months. Changes in urine cultures were also examined before and after the TAI treatments. In addition, correlation of gut microbiota and Bristol scale was analyzed. Significantly decreased abundance in Faecalibacterium, Blautia and Roseburia, and significantly increased abundance in Bacteroides and Roseburia were observed in the SB patients compared with controls and after TAI, respectively. The abundance of Roseburia was significantly correlated positively with Bristol scale. Urinary tract infection tended to decrease from 82% to 55% after TAI (p = 0.082) despite persistent fecal incontinence. Butyrate-producing bacteria such as Roseburia play a regulatory role in the intestinal motility and host immune system, suggesting the effects of TAI on gut microbiota.

PSIX-3 Comparison of 16S rRNA gene profiles of rumen microbiome from Raramuri Criollo, European and Criollo x European lineages

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 441-442
Author(s):  
Adrian Maynez-Perez ◽  
Francisco Jahuey-Martinez ◽  
Jose A Martinez-Quintana ◽  
Michael E Hume ◽  
Robin C Anderson ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Beta Diversity ◽  
Chihuahuan Desert ◽  
Reference Database ◽  
Rrna Gene ◽  
Linear Discriminant ◽  
Microbiome Composition ◽  
Northern Mexico ◽  
Rumen Microbiome

Abstract Raramuri Criollo cattle from the Chihuahuan desert in northern Mexico have been described as an ecological ecotype due to their enormous advantage in land grass utilization and their capacity to diversify their diet with cacti, forbs and woody plants. This diversification in diet utilization, could reflect upon their microbiome composition. The aim of this study was to characterize the rumen microbiome of Raramuri criollo cattle and to compare it to other lineages that graze in the same area. A total of 28 cows representing three linages [Criollo (n = 13), European (n = 9) and Criollo x European Crossbred (n = 6)] were grazed without supplementation for 45 days. DNA was extracted from ruminal samples and the V4 region of the 16S rRNA gene was sequenced on an Illumina platform. Data were analyzed with the QIIME2 software package and DADA2 plugin and the amplicon sequence variants were taxonomically classified with naïve Bayesian using the SILVA 16S rRNA gene reference database (version 132). Statistical analysis was performed by ANOVA and PERMANOVA for alpha and beta diversity indexes, respectively, and the non-strict version of linear discriminant analysis effect size (LEfSe) was used to determine significantly different taxa among lineages. Differences in beta diversity indexes (P &lt; 0.05) were found in ruminal microbiome composition between Criollo and European groups, whereas the Crossbred showed intermediate values when compared to the pure breeds (Table 1). LEfSe analysis identified a total of 20 bacterial groups that explained differences between lineages, including one for Crossbreed, ten for European and nine for Criollo. These results show ruminal microbiome differences between Raramuri criollo cattle and the mainstream European breeds used in the northern Mexico Chihuahuan desert and reflect that those differences could be a consequence of dissimilar grazing behavior.

Enrichment of IGF-1R and PPARγ signalling pathways in orbital inflammatory diseases: steps toward understanding pathogenesis

2021 ◽  
pp. bjophthalmol-2020-318330
Author(s):  
Rohan Verma ◽  
Dongseok Choi ◽  
Allison J Chen ◽  
Christina A Harrington ◽  
David J Wilson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Diseases ◽  
Target Therapy ◽  
Signalling Pathways ◽  
Peroxisome Proliferator ◽  
Healthy Controls ◽  
Gene Expressions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Orbital Inflammation ◽  
Wide Range

BackgroundOrbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy.AimsTo test the hypothesis that shared signalling pathways are activated in different forms of OID.MethodsIn this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls.ResultsAmong the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways.ConclusionsAlthough OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.

scholarly journals Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

2021 ◽  
Vol 10 (17) ◽  
pp. 3822
Author(s):  
Trung T. Vu ◽  
Hanako Koguchi-Yoshioka ◽  
Rei Watanabe
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Adaptive Immune Response ◽  
Psoriatic Skin ◽  
Peripheral Tissues ◽  
Potential Index ◽  
Circulating T Cells ◽  
Chronic Skin ◽  
Resident Memory T Cells

Tissue-resident memory T cells (TRM) stay in the peripheral tissues for long periods of time, do not recirculate, and provide the first line of adaptive immune response in the residing tissues. Although TRM originate from circulating T cells, TRM are physiologically distinct from circulating T cells with the expression of tissue-residency markers, such as CD69 and CD103, and the characteristic profile of transcription factors. Besides defense against pathogens, the functional skew of skin TRM is indicated in chronic skin inflammatory diseases. In psoriasis, IL-17A-producing CD8+ TRM are regarded as one of the pathogenic populations in skin. Although no licensed drugs that directly and specifically inhibit the activity of skin TRM are available to date, psoriatic skin TRM are affected in the current treatments of psoriasis. Targeting skin TRM or using TRM as a potential index for disease severity can be an attractive strategy in psoriasis.

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