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

Jordan Zeldin; Prem Prashant Chaudhary; Jacquelyn Spathies; Manoj Yadav; Brandon N. D’Souza; Mohammadali E. Alishahedani; Portia Gough; Jobel Matriz; Andrew J. Ghio; Yue Li; Ashleigh A. Sun; Lawrence F. Eichenfield; Eric L. Simpson; Ian A. Myles

doi:10.1126/sciadv.ade8898

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

Jordan Zeldin, Prem Prashant Chaudhary, Jacquelyn Spathies, Manoj Yadav, Brandon N. D’Souza, Mohammadali E. Alishahedani, Portia Gough, Jobel Matriz, Andrew J. Ghio, Yue Li, Ashleigh A. Sun, Lawrence F. Eichenfield, Eric L. Simpson, Ian A. Myles

Dermatology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	eade8898
Journal	Science Advances
Volume	9
Issue number	1
DOIs	https://doi.org/10.1126/sciadv.ade8898
State	Published - Jan 2023

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Zeldin, J., Chaudhary, P. P., Spathies, J., Yadav, M., D’Souza, B. N., Alishahedani, M. E., Gough, P., Matriz, J., Ghio, A. J., Li, Y., Sun, A. A., Eichenfield, L. F., Simpson, E. L., & Myles, I. A. (2023). Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria. Science Advances, 9(1), Article eade8898. https://doi.org/10.1126/sciadv.ade8898

Zeldin, J, Chaudhary, PP, Spathies, J, Yadav, M, D’Souza, BN, Alishahedani, ME, Gough, P, Matriz, J, Ghio, AJ, Li, Y, Sun, AA, Eichenfield, LF, Simpson, EL & Myles, IA 2023, 'Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria', Science Advances, vol. 9, no. 1, eade8898. https://doi.org/10.1126/sciadv.ade8898

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title = "Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria",

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.",

author = "Jordan Zeldin and Chaudhary, {Prem Prashant} and Jacquelyn Spathies and Manoj Yadav and D{\textquoteright}Souza, {Brandon N.} and Alishahedani, {Mohammadali E.} and Portia Gough and Jobel Matriz and Ghio, {Andrew J.} and Yue Li and Sun, {Ashleigh A.} and Eichenfield, {Lawrence F.} and Simpson, {Eric L.} and Myles, {Ian A.}",

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year = "2023",

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doi = "10.1126/sciadv.ade8898",

language = "English (US)",

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AU - Zeldin, Jordan

AU - Chaudhary, Prem Prashant

AU - Spathies, Jacquelyn

AU - Yadav, Manoj

AU - D’Souza, Brandon N.

AU - Alishahedani, Mohammadali E.

AU - Gough, Portia

AU - Matriz, Jobel

AU - Ghio, Andrew J.

AU - Li, Yue

AU - Sun, Ashleigh A.

AU - Eichenfield, Lawrence F.

AU - Simpson, Eric L.

AU - Myles, Ian A.

PY - 2023/1

Y1 - 2023/1

N2 - 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.

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

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