The human skin microbiome

Nature Reviews Microbiology, Год журнала: 2018, Номер 16(3), С. 143 - 155

Опубликована: Янв. 15, 2018

Язык: Английский

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Skin microbiota–host interactions

Nature, Год журнала: 2018, Номер 553(7689), С. 427 - 436

Опубликована: Янв. 25, 2018

Язык: Английский

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Establishing microbial composition measurement standards with reference frames

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Июнь 20, 2019

Abstract Differential abundance analysis is controversial throughout microbiome research. Gold standard approaches require laborious measurements of total microbial load, or absolute number microorganisms, to accurately determine taxonomic shifts. Therefore, most studies rely on relative data. Here, we demonstrate common pitfalls in comparing across samples and identify two solutions that reveal changes without the need estimate load. We define notion “reference frames”, which provide deep intuition about compositional nature In an oral time series experiment, reference frames alleviate false positives produce consistent results both raw cell-count normalized Furthermore, consistent, differentially abundant microbes previously undetected independent published datasets from subjects with atopic dermatitis. These methods allow reassessment data reproducible sequencing output for new assays.

Язык: Английский

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Pathophysiology of atopic dermatitis: Clinical implications

Allergy and Asthma Proceedings, Год журнала: 2019, Номер 40(2), С. 84 - 92

Опубликована: Март 1, 2019

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Genetic predisposition, epidermal barrier disruption, and dysregulation of immune system are some critical components AD. An impaired may be initial step in development atopic march as well AD, which leads to further inflammation allergic sensitization. Type 2 cytokines interleukin 17 22 contribute dysfunction New insights into pathophysiology AD have focused on lipid profiles, neuroimmune interactions, microbial dysbiosis. Newer therapeutic strategies focus improving function targeting polarized pathways found Further understanding will allow us achieve a more precision medicine approach prevention treatment

Язык: Английский

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Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical t

British Journal of Dermatology, Год журнала: 2017, Номер 178(5), С. 1083 - 1101

Опубликована: Ноя. 29, 2017

Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) widely used, potent immunosuppressant but it not effective in all patients with atopic dermatitis, and side‐effects limit its use. Dupilumab, fully human anti‐interleukin 4 receptor‐alpha monoclonal antibody, inhibits signaling of IL‐4 IL‐13, key drivers Type 2/Th2‐mediated inflammation, approved the U.S.A. European Union for treatment inadequately‐controlled moderate‐to‐severe adults. To evaluate efficacy safety dupilumab concomitant topical corticosteroids (TCS) adults inadequate response to/intolerance CsA, or whom CsA was medically inadvisable. In this 16‐week, double‐blind, randomized, placebo‐controlled, phase III trial, were randomized 1 : to subcutaneous 300 mg weekly (qw) every 2 weeks (q2w) placebo. All received medium‐potency TCS from Week −2 through 16; dosage could be tapered if lesions cleared, stopped adverse reactions TCS. total, 390 screened, 325 318 completed trial. Treatment groups had similar baseline characteristics. Significantly more qw + q2w achieved ≥ 75% improvement Eczema Area Severity Index at 16 vs. placebo group (primary end point) (59·1% 62·6% 29·6%, respectively; P < 0·001 TCS, both doses). Other clinical outcomes symptoms significantly improved groups, including pruritus, pain, sleep disturbance, anxiety depression, quality life (QoL). overall rates events (qw groups: 69·1%, 72·0% 69·4%, respectively) serious (1·8%, 1·9% 1·9%, respectively). Conjunctivitis frequent TCS; infections Dupilumab signs QoL history No new signals identified.

Язык: Английский

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Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship

Trends in Microbiology, Год журнала: 2017, Номер 26(6), С. 484 - 497

Опубликована: Дек. 9, 2017

Язык: Английский

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The microbiome in patients with atopic dermatitis

Journal of Allergy and Clinical Immunology, Год журнала: 2018, Номер 143(1), С. 26 - 35

Опубликована: Ноя. 23, 2018

As an interface with the environment, skin is a complex ecosystem colonized by many microorganisms that coexist in established balance. The cutaneous microbiome inhibits colonization pathogens, such as Staphylococcus aureus, and crucial component for function of epidermal barrier. Moreover, crosstalk between commensals immune system now recognized because can modulate both innate adaptive responses. Host-commensal interactions also have effect on developing infants and, subsequently, occurrence diseases, asthma atopic dermatitis (AD). Later life, contributes to development course disease. Accordingly, patients AD, decrease diversity correlates disease severity increased pathogenic bacteria, S aureus. Early clinical studies suggest topical application commensal organisms (eg, hominis or Roseomonas mucosa) reduces AD severity, which supports important role decreasing aureus AD. Advancing knowledge its modulating disorders, might result novel therapeutic strategies. A multitude microbiota inhabit our human epithelial surfaces. Although there increasing evidence these microbiota, live bodies, are health disease, functions consequences resident remain poorly understood. Given challenges being able adequately culture all microbes present given sample, technological advances genome sequencing ability interrogate microbiomes (the full collection microbiota). Several technical study composition collectively enlightened understanding pathogenesis (AD) modification (Fig 1).1Byrd A.L. Belkaid Y. Segre J.A. microbiome.Nat Rev Microbiol. 2018; 16: 143-155Crossref PubMed Scopus (917) Google Scholar animal models cannot fully recapitulate states, use model deeply investigate host-microbial relationships has elucidated intriguing biological mechanisms. continued integration gleaned from patient-derived models, will be critical approaches. Prior publications extensively reviewed differences based various factors, including anatomic sites, sexual maturity, physiology; this review provides broad overview different aspects microbiome, immunology, microbiology, barrier research related particular early host-microbiome events Here we healthy skin. complexities microbial communities reflected distinct observed skin, gut, respiratory tract, among other body sites. Furthermore, niches undergo changes over lifespan. continual potential roles subsequently lead preventative and/or Skin highlighted site specificity subjects, regional surfaces compositions communities.2Findley K. Oh J. Yang Conlan S. Deming C. Meyer et al.Topographic fungal bacterial skin.Nature. 2013; 498: 367-370Crossref (731) Scholar, 3Grice E.A. Kong H.H. C.B. Davis Young A.C. al.Topographical temporal microbiome.Science. 2009; 324: 1190-1192Crossref (1840) 4Oh Byrd NISC program al.Biogeography individuality shape metagenome.Nature. 2014; 514: 59-64Crossref (624) 5Costello E.K. Lauber C.L. Hamady M. Fierer N. Gordon J.I. Knight R. Bacterial community variation habitats across space time.Science. 326: 1694-1697Crossref (2181) hosts most diverse body, more than 1000 species 19 phyla.3Grice 6Kong molecular revolution biology: investigating microbiome.J Invest Dermatol. 2017; 137: e119-e122Abstract Full Text PDF (31) unique features specific some shared reflect physiology: sebaceous sites often Cutibacterium acnes (formerly known Propionibacterium acnes). Small adult volunteers shown relatively stable months years each person possess personalized microbiome.7Oh Park Comparative Sequencing Program Temporal stability microbiome.Cell. 2016; 165: 854-866Abstract (495) Studies demonstrated subjects at life stages. For example, children who less sexually mature lower relative abundances Corynebacterium species8Oh Polley E.C. Shifts nares adults.Genome Med. 2012; 4: 77Crossref (224) greater fungi9Jo J.H. Kennedy Ng W.L. al.Diverse converge adulthood.J 136: 2356-2363Abstract (86) compared subjects. infant particularly active area investigation it provide insights into early-life exposures.10Capone K.A. Dowd S.E. Stamatas G.N. Nikolovski Diversity life.J 2011; 131: 2026-2032Abstract (302) 11Costello Carlisle E.M. Bik Morowitz M.J. Relman D.A. Microbiome assembly multiple low-birthweight infants.MBio. 4 (e00782-13)Crossref (106) 12Dominguez-Bello M.G. Costello Contreras Magris Hidalgo G. al.Delivery mode shapes acquisition structure initial newborns.Proc Natl Acad Sci U A. 2010; 107: 11971-11975Crossref (2958) 13Kennedy Connolly Hourihane J.O. Fallon P.G. McLean W.H. Murray D. al.Skin before dermatitis: staphylococci 2 associated risk 1 year.J Allergy Clin Immunol. 139: 166-172Abstract (206) Children young days old site-specific their microbiomes13Kennedy influence future disease.14Shi B. Bangayan N.J. Curd E. Taylor P.A. Gallo R.L. Leung D.Y.M. al.The pediatric versus dermatitis.J 138: 1233-1236Abstract (92) 15Chu D.M. Ma Prince Antony K.M. Seferovic M.D. Aagaard Maturation relation delivery.Nat 23: 314-326Crossref (556) characterized rapid immunologic maturation. such, represents period during host-commensal formatively affect how responds brethren.16Kollmann T.R. Levy O. Montgomery R.R. Goriely Innate Toll-like receptors: responses newborns elderly.Immunity. 37: 771-783Abstract (378) 17McGovern Shin Low Duan Yao L.J. al.Human fetal dendritic cells promote prenatal T-cell suppression through arginase-2.Nature. 546: 662-666Crossref (157) Future success microbially directed interventions prevent treat inflammatory require deeper mechanisms responsible symbiosis window. Neonatal demonstrate reduced propensity activation inflammation those adults. We appreciate not only due immaturity but existence regulatory In infants, older adults, receptors (TLRs), key sensors system, results production IL-6 IL-23 TNF-α IL-1.16Kollmann Composition evolves parallel, T (Treg) found abundance infancy.17McGovern 18Yang Fujikado Kolodin Benoist Mathis Immune tolerance. Regulatory generated play maintaining self-tolerance.Science. 2015; 348: 589-594Crossref (283) 19Thome J.J.C. Bickham K.L. Ohmura Kubota Matsuoka al.Early-life compartmentalization cell differentiation mucosal lymphoid tissues.Nat 22: 72-77Crossref (201) place neonates disseminated infection, they tolerance self-antigens foreign antigens, thereby preventing disadvantageous tissue development. Birth marks abrupt transition, exposure products antigens. seen later influenced, least initially, exogenous birth delivery maternal commensals.10Capone Notably, identity host trajectory. gut- lung-resident been susceptibility colitis, asthma, anaphylaxis.20Gensollen T. Iyer S.S. Kasper D.L. Blumberg R.S. How system.Science. 352: 539-544Crossref (956) presence absence certain gut bacteria proinflammatory metabolites heightened asthma.21Fujimura K.E. Sitarik A.R. Havstad Lin Levan Fadrosh al.Neonatal associates childhood multisensitized atopy differentiation.Nat 1187-1191Crossref (586) Whether disruption directly affects remains open question. However, notable recent longitudinal examining alterations flora predate onset.13Kennedy 22Meylan P. Lang Mermoud Johannsen Norrenberg Hohl precedes diagnosis infancy.J 2497-2504Abstract (143) Until recently, little was about exposures function. Modeling relationship mice taught us likely equal significance tissues. When neonatal bacterium (coagulase-negative [CoNS]) epidermidis, develop large percentage Treg epidermidis mount microbe rechallenge life. contrast, delaying until adulthood prevents protective promotes otherwise "healthy" 2).22Meylan At factor accounting age-dependent difference density skin.23Scharschmidt T.C. Vasquez K.S. Truong H.-A. Gearty S.V. Pauli M.L. Nosbaum al.A wave t mediates microbes.Immunity. 43: 1011-1021Abstract (328) Intriguingly, markedly decreased raised under gnotobiotic ("germ-free") conditions lacking hair follicles, major niche CoNS species. Indeed, follicles appears stimulate isthmus keratinocytes chemokine, CCL20, then helps recruit 2, left panel).24Scharschmidt Leitner E.G. Chu al.Commensal follicle morphogenesis coordinately drive migration skin.Cell Host Microbe. 21: 467-477Abstract (145) Thus promoting establishment preferentially facilitated themselves. Of course, regard timing development, communities, structure. findings translate biology implications disrupting fruitful investigation. detailed phenotyping yet undertaken, enriched skin.25Cordoro Hitraya-Low Taravati Sandoval P.M. Kim Sugarman al.Skin-infiltrating, interleukin-22-producing differentiate psoriasis psoriasis.J Am 77: 417-424Abstract (33) considering translational applications research, one envision corrective measures reduce onset mitigate severity. latter especially relevant variable penetrance genetic age defining features.26Weidinger Beck L.A. Bieber Kabashima Irvine A.D. Atopic dermatitis.Nat Dis Primers. 1Crossref (273) Continued work define function, context barrier-disrupted inform prevention-oriented recommendations microbe-based interventions. presents physical harmful agents while establishing regulate communities. contrast surfaces, maintain separation mucous layer, dense distribution appendages creates surface close communication microbes.27Gallo Human largest interaction microbes.J 1213-1214Abstract (124) strictly regulates sophisticated set antimicrobial gene include peptides proteins, lipids, pH barrier, free radical control community.28Zhang Antimicrobial peptides.Curr Biol. 26: R14-R19Abstract (518) network patrol reinforce pathogens penetrate epidermis after even minor breach.29Nakatsuji Chiang H.I. Jiang S.B. Nagarajan H. Zengler extends subepidermal compartments normal skin.Nat Commun. 1431Crossref (303) interplay defense, emerged balance disease.30Williams M.R. Nakatsuji aureus: master manipulator 579-581Abstract (41) 31Belkaid Dialogue immunity.Science. 346: 954-959Crossref (371) Mounting experimental suggests efficacious treatment conditions.32Grice microbiome: diagnostic approaches disease.Semin Cutan Med Surg. 33: 98-103Crossref (135) fundamental underlying immune-commensal beginning unfold. nuanced factors immunity offers opportunity harness power benefit. germ-free revealed optimal requires cues indigenous 2).33Naik Bouladoux Wilhelm Molloy Salcedo Kastenmuller W. al.Compartmentalized commensals.Science. 337: 1115-1119Crossref instance, effector make cytokines, IL-17A IFN-γ, dramatically abrogated commensals. This defect restored association commensal, residing intestine, highlighting nonredundant skin-resident modulation.33Naik 34Belkaid Naik Compartmentalized systemic commensals.Nat 14: 646-653Crossref (243) controls co-opting existing pathways, case IL-1α cells. skin-derived signals dispensable specification lymph node, commensally induced molecules entry sustain functions. Importantly, homeostatic tuning occurs overt intact barrier.35Naik Linehan J.L.1 Han S.J. Harrison O.J. Commensal-dendritic-cell specifies signature.Nature. 520: 104-108Crossref (470) lines advantageous support rich milieu elicit types Defined strains induce IL-17A, producing CD8 (TC17) reside epidermis.35Naik population actively cell–dependent antigen presentation N-formyl methionine peptides.36Linehan J.L. Vujkovic-Cvijin I. Villarino A.V. al.Non-classical impact repair.Cell. 172: 784-796Abstract (225) line findings, tropic produce IFN-γ response stimulation antigen.37Schlapbach Gehad Watanabe Guenova Teague J.E. TH9 skin-tropic autocrine paracrine capacity.Sci Transl 6: 219ra8Crossref TC17 constitutively skin33Naik 38Clark R.A. Resident memory disease.Sci 7: 269rv1Crossref squamous carcinomas39Roberts B.Y. Filler R.B. Lewis Glusac E.J. Hayday al.Characterizing tumor-promoting chemically carcinogenesis.Proc 2007; 104: 6770-6775Crossref (59) psoriatic plaques,40Cheuk Wikén Blomqvist L. Nylén Talme Ståhle al.Epidermal Th22 Tc17 form localized clinically healed 192: 3111-3120Crossref (227) suggesting contribute demonstration TH17-driven expression significantly Th17-related lesional nonlesional recent-onset potentially environmental commensals.41Brunner Israel Zhang Leonard Wen H.C. Huynh al.Early-onset TH2/TH17/TH22-centered lipid alterations.J 141: 2094-2106Abstract (139) 42Esaki Brunner Renert-Yuval Czarnowicki Tran TH2 TH17 polarized skin.J 1639-1651Abstract (240) Specificity limited cognate first description benefit came identification chemical moieties displayed interact TLR2 ligand, lipoteichoic acid, strain uniquely dampen inflammation.43Lai Di Nardo Leichtle Cogen Wu Z.R. receptor 3-dependent injury.Nat 5: 1377-1382Crossref (514) enhance defense enhancing peptide expression.44Lai Radek H.J. Macleod D.T. al.Activation small molecule produced increases against infections.J 130: 2211-2221Abstract (289) members genus envelope mycolic specifically IL-17A+ dermal γδ 2).45Ridaura V.K. Claesen Chen Y.E. Constantinides al.Contextual Corynebacterium.J Exp 215: 785-799Crossref By CD4+ programs broadly triggered wide array colonization.35Naik tempting speculate evolved sense complexity information rheostat continuously calibrate myriad elicited several contextual reinforcing Commensal-specific help heterologous protection pathogens. augmenting commensal-specific limit Candida albicans, establish infections.35Naik interac

Язык: Английский

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The social network of microorganisms — how auxotrophies shape complex communities

Nature Reviews Microbiology, Год журнала: 2018, Номер 16(6), С. 383 - 390

Опубликована: Март 29, 2018

Язык: Английский

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Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair

Cell, Год журнала: 2018, Номер 172(4), С. 784 - 796.e18

Опубликована: Янв. 18, 2018

Язык: Английский

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Host–microbiota interactions in immune-mediated diseases

Nature Reviews Microbiology, Год журнала: 2020, Номер 18(9), С. 521 - 538

Опубликована: Май 26, 2020

Язык: Английский

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