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American Journal of Clinical Dermatology Feb 2020The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use...
BACKGROUND
The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea.
OBJECTIVE
We performed a case-control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race.
METHODS
Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software.
RESULTS
Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%).
CONCLUSIONS
The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.
Topics: Adult; Aged; Bacteria; Case-Control Studies; Female; Humans; Male; Microbiota; Middle Aged; Rosacea; Skin; Young Adult
PubMed: 31502207
DOI: 10.1007/s40257-019-00471-5 -
PloS One 2023We recently used EPA databases to identify that isocyanates, most notably toluene diisocyanate (TDI), were the pollutant class with the strongest spatiotemporal and...
We recently used EPA databases to identify that isocyanates, most notably toluene diisocyanate (TDI), were the pollutant class with the strongest spatiotemporal and epidemiologic association with atopic dermatitis (AD). Our findings demonstrated that isocyanates like TDI disrupted lipid homeostasis and modeled benefit in commensal bacteria like Roseomonas mucosa through disrupting nitrogen fixation. However, TDI has also been established to activate transient receptor potential ankyrin 1 (TRPA1) in mice and thus could directly contribute to AD through induction of itch, rash, and psychological stress. Using cell culture and mouse models, we now demonstrate that TDI induced skin inflammation in mice as well as calcium influx in human neurons; each of these findings were dependent on TRPA1. Furthermore, TRPA1 blockade synergized with R. mucosa treatment in mice to improve TDI-independent models of AD. Finally, we show that the cellular effects of TRPA1 are related to shifting the balance of the tyrosine metabolites epinephrine and dopamine. This work provides added insight into the potential role, and therapeutic potential, or TRPA1 in the pathogenesis of AD.
Topics: Humans; Animals; Mice; Dermatitis, Atopic; Exanthema; Pruritus; Isocyanates; Toluene 2,4-Diisocyanate; Cytoskeletal Proteins; TRPA1 Cation Channel
PubMed: 36877675
DOI: 10.1371/journal.pone.0282569 -
Science Advances Jan 2023Atopic dermatitis (AD) is a chronic inflammatory skin condition increasing in industrial nations at a pace that suggests environmental drivers. We hypothesize that the...
Atopic dermatitis (AD) is a chronic inflammatory skin condition increasing in industrial nations at a pace that suggests environmental drivers. We hypothesize that the dysbiosis associated with AD may signal microbial adaptations to modern pollutants. Having previously modeled the benefits of health-associated , we now show that fixes nitrogen in the production of protective glycerolipids and their ceramide by-products. Screening EPA databases against the clinical visit rates identified diisocyanates as the strongest predictor of AD. Diisocyanates disrupted the production of beneficial lipids and therapeutic modeling for isolates of as well as commensal . Last, while topical failed to meet commercial end points in a placebo-controlled trial, the subgroup who completed the full protocol demonstrated sustained, clinically modest, but statistically significant clinical improvements that differed by study site diisocyanate levels. Therefore, diisocyanates show temporospatial and epidemiological association with AD while also inducing eczematous dysbiosis.
Topics: Humans; Dermatitis, Atopic; Dysbiosis; Isocyanates; Prevalence; Bacteria; Skin
PubMed: 36608129
DOI: 10.1126/sciadv.ade8898 -
Microbiology Resource Announcements Nov 2023is a bacterium that is found in the natural microbiota of human skin. Here, we present sequence assemblies from isolated from the skin microflora of three healthy...
is a bacterium that is found in the natural microbiota of human skin. Here, we present sequence assemblies from isolated from the skin microflora of three healthy human volunteers that were used to treat atopic dermatitis patients.
PubMed: 37819097
DOI: 10.1128/MRA.00520-23 -
Skin Health and Disease Sep 2021While patients and families struggling with atopic dermatitis (AD) have documented concerns for a contributory role of skin care products in AD pathology, nearly all the...
BACKGROUND
While patients and families struggling with atopic dermatitis (AD) have documented concerns for a contributory role of skin care products in AD pathology, nearly all the skin microbiome studies to date have asked participants to avoid topical products (such as soaps or select medications) for the preceding days to weeks prior to sample collection. Thus, given the established role of the microbiome in AD, the interactions between topical exposures, dysbiosis and AD remains underrepresented in the academic literature.
OBJECTIVES
To address this knowledge gap, we expanded our previous evaluations to test the toxicological effects of a broader range of common chemicals, AD treatment lotions, creams and ointments using both health- and AD-associated strains of and spp.
METHODS
Use of in vitro culture techniques and mouse models were deployed to identify chemicals with dysbiotic or pre-biotic potential. A proof-of-concept study was subsequently performed in healthy volunteers to assess global microbiome shifts after exposure to select chemicals using dermatologic patch testing.
RESULTS
Numerous chemicals possessed antibiotic properties, including many not marketed as anti-microbials. Through targeted combination of potentially beneficial chemicals, we identified combinations which promoted the growth of health-associated isolates over disease-associated strains in bacterial culture and enhanced microbe-specific outcomes in an established mouse model of AD; the most promising of which was the combination of citral and colophonium (often sold as lemon myrtle oil and pine tar). Additional studies would likely further optimize the combination of ingredients use. Similar results were seen in the proof-of-concept human studies.
CONCLUSIONS
Our results could offer a systematic, multiplex approach to identify which products carry dysbiotic potential and thus may guide formulation of new topicals to benefit patients with AD.
PubMed: 34723253
DOI: 10.1002/ski2.41 -
MSystems Mar 2024Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for...
Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. species, especially , were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example sp., sp., , , sp., sp., , , , and , in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.
Topics: Adult; Humans; Dermatitis, Atopic; Staphylococcus aureus; RNA, Ribosomal, 16S; Microbiota; Metabolome; Bacteria; Dipeptides
PubMed: 38319107
DOI: 10.1128/msystems.01119-23 -
Communications Medicine Apr 2024Atopic dermatitis (AD) is a chronic, inflammatory disease characterized by dry, pruritic skin. In the U.S., the prevalence of AD has increased over three-fold since the...
BACKGROUND
Atopic dermatitis (AD) is a chronic, inflammatory disease characterized by dry, pruritic skin. In the U.S., the prevalence of AD has increased over three-fold since the 1970s. We previously reported a geographic association between isocyanate-containing air pollution and AD as well as mechanistic data demonstrating that isocyanates induce skin dysbiosis and activate the host itch receptor TRPA1. However, non-spatial models are susceptible to spatial confounding and may overlook other meaningful associations.
METHODS
We added spatial analysis to our prior model, contrasting pollution data with clinical visits. In addition, we conducted a retrospective case-control survey of childhood exposure to BTEX-related products. Finally, we assessed implicated compounds, in pure form and as part of synthetic fabric, for their effect on the growth and metabolism of skin commensal bacteria.
RESULTS
Spatial analysis implicate benzene, toluene, ethylbenzene, and, most significantly, xylene (BTEX) compounds. Survey odds ratios for AD were significant for xylene-derived polyester bed sheets (OR = 9.5; CI 2.2-40.1) and diisocyanate-containing wallpaper adhesive (OR = 6.5; CI 1.5-27.8). Staphylococcus aureus lives longer on synthetic textiles compared to natural textiles. Meanwhile, synthetic fabric exposure shifts the lipid metabolism of health-associated commensals (Roseomonas mucosa and S. epidermidis) away from therapeutic pathways.
CONCLUSIONS
We propose that BTEX chemicals in their raw forms and in synthetic products represent a unifying hypothesis for environmentally induced AD flares through their ability to create dysbiosis in the skin microbiota and directly activate TRPA1. Unequal distribution of these pollutants may also influence racial disparities in AD rates.
PubMed: 38637696
DOI: 10.1038/s43856-024-00500-3 -
Environmental Science & Technology... May 2023Compared to the myriad of known triggers for rhinitis and asthma, environmental exposure research for atopic dermatitis (AD) is not well established. We recently...
Compared to the myriad of known triggers for rhinitis and asthma, environmental exposure research for atopic dermatitis (AD) is not well established. We recently reported that an untargeted search of U.S. Environmental Protection Agency (EPA) databases versus AD rates by United States (U.S.) postal codes revealed that isocyanates, such as toluene diisocyanate (TDI), are the pollutant class with the strongest spatiotemporal and epidemiologic association with AD. We further demonstrated that (di)isocyanates disrupt ceramide-family lipid production in commensal bacteria and activate the thermo-itch host receptor TRPA1. In this report, we reanalyzed regions of the U.S. with low levels of diisocyanate pollution to assess if a different chemical class may contribute. We identified antimony compounds as the top associated pollutant in such regions. Exposure to antimony compounds would be expected from brake dust in high-traffic areas, smelting plants, bottled water, and dust from aerosolized soil. Like TDI, antimony inhibited ceramide-family lipid production in and activated TRPA1 in human neurons. While further epidemiologic research will be needed to directly evaluate antimony exposure with surrounding AD prevalence and severity, these data suggest that compounds which are epidemiologically associated with AD, inhibit commensal lipid production, and activate TRPA1 may be causally related to AD pathogenesis.
PubMed: 37692200
DOI: 10.1021/acs.estlett.3c00142 -
Journal of Clinical Medicine Feb 2020Despite several methods having been described for disinfecting implants affected by periimplantitis, none of these are universally effective and may even alter surfaces...
Despite several methods having been described for disinfecting implants affected by periimplantitis, none of these are universally effective and may even alter surfaces and mechanical properties of implants. Boron-doped diamond (BDD) electrodes were fabricated from niobium wires and assembled as a single instrument for implant cleaning. Chemo-mechanical debridement and air abrasion were used as control methods. Different mono-species biofilms, formed by bacteria and yeasts, were allowed to develop in rich medium at 37 °C for three days. In addition, natural multi-species biofilms were treated. Implants were placed in silicone, polyurethane foam and bovine ribs for simulating different clinical conditions. Following treatment, the implants were rolled on blood agar plates, which were subsequently incubated at 37 °C and microbial growth was analyzed. Complete electrochemical disinfection of implant surfaces was achieved with a maximum treatment time of 20 min for , , , , and , while in case of spore-forming and , a number of colonies appeared after BDD electrode treatment indicating an incomplete disinfection. Independent of the species tested, complete disinfection was never achieved when conventional techniques were used. During treatment with BDD electrodes, only minor changes in temperature and pH value were observed. The instrument used here requires optimization so that higher charge quantities can be applied in shorter treatment times.
PubMed: 32050444
DOI: 10.3390/jcm9020475 -
Bioactive Materials Mar 2023Many skin diseases, such as atopic dermatitis (AD), are featured with the dysbiosis of skin microbiota. The clinically recommended options for AD treatments suffer from...
Many skin diseases, such as atopic dermatitis (AD), are featured with the dysbiosis of skin microbiota. The clinically recommended options for AD treatments suffer from poor outcomes and high side-effects, leading to severe quality-of-life impairment. To deal with this long-term challenge, we develop a living bacterial formulation (Hy@Rm) that integrates skin symbiotic bacteria of with poly(vinyl pyrrolidone), poly(vinyl alcohol) and sodium alginate into a skin dressing by virtue of the Ca-mediated cross-linking and the freezing-thawing (F-T) cycle method. Hy@Rm dressing creates a favorable condition to not only serve as extrinsic culture harbors but also as nutrient suppliers to support . survival in the harsh microenvironment of AD sites to defeat which predominantly colonizes AD skins as an indigenous pathogen, mainly through the secretion of sphingolipids metabolites by . like a therapeutics bio-factory. Meanwhile, this elaborately designed skin dressing could accelerate wound healing, normalize aberrant skin characters, recover skin barrier functions, alleviate AD-associated immune/inflammation responses, functioning like a combinational therapy. This study offers a promising means for the topical bacteria transplant to realize effective microbe biotherapy toward the skin diseases feature with microbe milieu disorders, including but not limited to AD disease.
PubMed: 36157249
DOI: 10.1016/j.bioactmat.2022.08.019