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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 -
Frontiers in Immunology 2022The cutaneous microbiome is increasingly recognized as a contributor to skin diseases like atopic dermatitis (AD) and psoriasis. Although traditionally AD and psoriasis...
The cutaneous microbiome is increasingly recognized as a contributor to skin diseases like atopic dermatitis (AD) and psoriasis. Although traditionally AD and psoriasis have been viewed as having opposing immunologic findings, recent evidence suggests an overlap in ceramide-family lipid production in the protection against symptoms. We recently identified that specific environmental pollutants may drive dysbiosis through direct suppression of ceramide-family lipids produced by health-associated skin bacteria in atopic dermatitis (AD). We further demonstrated that one such bacteria, , generated significant clinical improvement in AD lasting beyond active treatment lipid-mediated modulation of tumor necrosis factor (TNF) signaling. To assess the potential preclinical benefit of in psoriasis we assessed for direct effects on surface TNF signaling in cell cultures and identified direct effects on the TNF axis. We also identified preclinical efficacy of treatment in the imiquimod mouse model of psoriasis. Finally, we expanded our previous environmental assessment for psoriasis to include more traditional markers of air quality and found a strong association between disease rates and ambient carbon monoxide (CO), nitrogen dioxide (NO), and particulate matter (PM). At the current stage this work is speculative but does support consideration of further preclinical models and/or clinical assessments to evaluate any potential for therapeutic benefit through microbial manipulation and/or environmental mitigation.
Topics: Animals; Mice; Dermatitis, Atopic; Environmental Pollutants; Psoriasis; Ceramides; Lipids
PubMed: 36605199
DOI: 10.3389/fimmu.2022.1094376 -
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 -
BMJ Case Reports Mar 2022Hepatic abscesses can rarely cause pericardial disease by erosion into the pericardial space and present with haemodynamic instability due cardiac tamponade. While rare,...
Hepatic abscesses can rarely cause pericardial disease by erosion into the pericardial space and present with haemodynamic instability due cardiac tamponade. While rare, these dramatic presentations are more often due to amoebic abscesses than bacterial abscesses. Importantly, a cause must be found for any cryptogenic hepatic abscess regardless of presentation, as there is a high association with underlying malignancy. We report a previously healthy man in his 30s who presented with cardiac tamponade from perforation of a pyogenic hepatic abscess into the pericardium in the absence of bacteremia and biliary disease. One year later, he was found to have diffusely metastatic hepatoid carcinoma.
Topics: Adenocarcinoma; Cardiac Tamponade; Humans; Liver Abscess, Pyogenic; Male; Methylobacteriaceae
PubMed: 35304358
DOI: 10.1136/bcr-2022-248947 -
Case Reports in Nephrology 2021species, a rare Gram-negative microorganism, has seldom been reported to cause peritonitis in end-stage renal disease patients on peritoneal dialysis. Only seven cases...
species, a rare Gram-negative microorganism, has seldom been reported to cause peritonitis in end-stage renal disease patients on peritoneal dialysis. Only seven cases of peritonitis by this rare microorganism have been reported worldwide. Treatment options can be challenging if not detected early and can lead to significant morbidity and mortality along with the switching of the dialysis modality to hemodialysis which is highly undesirable. Our patient is a 65-year-old Caucasian female who needed to be changed to emergency hemodialysis due to inability to perform peritoneal dialysis from suspected peritonitis and was subsequently discovered to have peritonitis from . She recovered with a prolonged antibiotics course and returned to peritoneal dialysis in 3 months following her treatment completion. Prompt diagnosis and prolonged antibiotics are a cornerstone in the management of this rare microorganism to prevent mortality and morbidity from peritonitis.
PubMed: 34760324
DOI: 10.1155/2021/1979332 -
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 -
Access Microbiology Mar 2021Both bacterial and aseptic meningitis can complicate neurosurgery, but they are often difficult to distinguish clinically or by cerebrospinal fluid (CSF) analysis. We...
Both bacterial and aseptic meningitis can complicate neurosurgery, but they are often difficult to distinguish clinically or by cerebrospinal fluid (CSF) analysis. We present an adolescent with subacute meningitis after neurosurgery, eventually diagnosed with meningitis caused by via 16S rRNA gene sequencing after two negative CSF cultures. He was treated successfully with intravenous meropenem with full recovery. This case shows that distinguishing bacterial from aseptic meningitis is important to allow directed antibiotic therapy. We recommend considering bacterial meningitis in the differential diagnosis of aseptic meningitis complicating neurosurgery, and to perform molecular diagnostics such as bacterial sequencing if the suspicion of bacterial meningitis is high.
PubMed: 34151165
DOI: 10.1099/acmi.0.000213 -
Science Translational Medicine Sep 2020Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety... (Randomized Controlled Trial)
Randomized Controlled Trial
Dysbiosis of the skin microbiota is increasingly implicated as a contributor to the pathogenesis of atopic dermatitis (AD). We previously reported first-in-human safety and clinical activity results from topical application of the commensal skin bacterium for the treatment of AD in 10 adults and 5 children older than 9 years of age. Here, we examined the potential mechanism of action of treatment and its impact on children with AD less than 7 years of age, the most common age group for children with AD. In 15 children with AD, treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced burden on the skin, and a reduction in topical steroid requirements without severe adverse events. Our observed response rates to treatment were greater than those seen in historical placebo control groups in prior AD studies. Skin improvements and colonization by persisted for up to 8 months after cessation of treatment. Analyses of cellular scratch assays and the MC903 mouse model of AD suggested that production of sphingolipids by , cholinergic signaling, and flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. These results suggest that a randomized, placebo-controlled trial of treatment in individuals with AD is warranted and implicate commensals in the maintenance of the skin epithelial barrier.
Topics: Adult; Child; Dermatitis, Atopic; Eczema; Humans; Lipids; Methylobacteriaceae; Skin
PubMed: 32908007
DOI: 10.1126/scitranslmed.aaz8631 -
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