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      Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria

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          Abstract

          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 Roseomonas mucosa, we now show that R. mucosa 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 R. mucosa as well as commensal Staphylococcus. Last, while topical R. mucosa 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.

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          Abstract

          Diisocyanates exhibited the strongest temporospatial and epidemiological association with eczema and induced eczematous dysbiosis.

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          Regularization Paths for Generalized Linear Models via Coordinate Descent

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            ranger: A Fast Implementation of Random Forests for High Dimensional Data in C++ and R

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              Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania

              Humans have co-speciated with their gut-resident microbes, but it is difficult to infer features of our ancestral microbiome. Here, we examine the microbiome profile of 350 stool samples collected longitudinally for over a year from the Hadza hunter-gatherers of Tanzania. The data reveal annual cyclic reconfiguration of the microbiome, in which some taxa become undetectable only to reappear in a subsequent season. Comparison of the Hadza dataset with data collected from 18 populations in 16 countries with varying lifestyles reveals that gut community membership corresponds to modernization: Notably, the taxa within the Hadza that are the most seasonally volatile similarly differentiate industrialized and traditional populations. These data indicate that some dynamic lineages of microbes have decreased in prevalence and abundance in modernized populations.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing - review & editing
                Role: InvestigationRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing - review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing - review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing - review & editing
                Role: ConceptualizationRole: Investigation
                Role: InvestigationRole: MethodologyRole: Writing - review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing - original draft
                Role: InvestigationRole: MethodologyRole: ResourcesRole: Writing - review & editing
                Role: Data curationRole: InvestigationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Methodology
                Role: ConceptualizationRole: VisualizationRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Journal
                Sci Adv
                Sci Adv
                sciadv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                January 2023
                06 January 2023
                : 9
                : 1
                : eade8898
                Affiliations
                [ 1 ]Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
                [ 2 ]U.S. Environmental Protection Agency, Chapel Hill, NC, USA.
                [ 3 ]Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
                [ 4 ]Departments of Dermatology and Pediatrics, University of California San Diego, La Jolla, CA, USA.
                [ 5 ]Rady Children’s Hospital, San Diego, CA, USA.
                [ 6 ]Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
                Author notes
                [* ]Corresponding author. Email: mylesi@ 123456niaid.nih.gov
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3259-1381
                https://orcid.org/0000-0002-3467-8608
                https://orcid.org/0000-0002-7731-1363
                https://orcid.org/0000-0002-3507-0362
                https://orcid.org/0000-0003-0201-7597
                https://orcid.org/0000-0003-0502-6448
                https://orcid.org/0000-0002-1874-2999
                https://orcid.org/0000-0002-5648-0723
                https://orcid.org/0000-0002-2760-0474
                https://orcid.org/0000-0003-0853-0252
                https://orcid.org/0000-0001-9316-3703
                Article
                ade8898
                10.1126/sciadv.ade8898
                9821876
                36608129
                efc31d2b-0039-44c3-8ec6-aeff15482f53
                Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 14 September 2022
                : 05 December 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: Intramural
                Categories
                Research Article
                Biomedicine and Life Sciences
                SciAdv r-articles
                Health and Medicine
                Environmental Studies
                Environmental Studies
                Custom metadata
                Penchie Limbo

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