title: Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis.
abstract: Psoriasis is an inflammatory skin disease affecting ∼2% of the world's population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing γδ(+) T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis.
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Zanvit
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.|University of Manchester, Faculty of Life Sciences, Manchester, M13 9PT, UK.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Konkel
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.|Center of Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan 250001, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Kasagi
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Dunfang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.|State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Wu
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chia
authors.affiliation: The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.affiliation: The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Daniel P
authors.identifier: http://orcid.org/0000-0002-2479-2044
authors.initials: DP
authors.lastname: Smith
authors.affiliation: The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Abbatiello
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakatsukasa
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.affiliation: Center of Reproductive Medicine, Shandong Provincial Hospital, Shandong University, Jinan 250001, China.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, Maryland 20892, USA.
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004198:Disease Susceptibility; D004347:Drug Interactions; D000077271:Imiquimod; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects*; D011112:Polymyxin B / Q000009:adverse effects*; D011565:Psoriasis / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism; D014640:Vancomycin / Q000009:adverse effects*; D000097043:Interleukin-22
chemical_list: D000634:Aminoquinolines; D000900:Anti-Bacterial Agents; D000077271:Imiquimod; D020381:Interleukin-17; D007378:Interleukins; D011112:Polymyxin B; D014640:Vancomycin; D000097043:Interleukin-22