Manipulating Microbiota to Treat Atopic Dermatitis: History
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Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Md Jahangir Alam
,
Liang Xie
,
Yu-Anne Yap
,
,
Remy Robert

Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. Thus, radically different approaches are needed to address a significant unmet need in AD patients. A novel promising therapeutic target for AD is the microbiota.

  • atopic dermatitis
  • skin microbiota
  • gut microbiota
  • metabolites
  • short-chain fatty acids (SCFAs)
  • G-protein coupled receptors (GPCRs)
  • histone deacetylases (HDACs)
  • toll-like receptors (TLRs)
  • Staphylococcus aureus

1. Introduction

Atopic dermatitis (AD), also known as eczema, is a skin inflammation that exhibits chronic, persistent, pruritic lesions, and is often associated elevated levels of IgE [1][2]. AD affects 10–20% of the population during their lifetime in developed countries, with a particularly high prevalence among children [2][3]. Its prevalence is also rapidly increasing in developing nations [4][5]. The established pathogenesis of AD involves the initiation of barrier disruption, followed by the activation of type 2 (TH2) immune responses [2][6]. Variants in the filaggrin (FLG), the gene encoding an important skin barrier protein, represent a significant risk factor for AD [7][8][9]. AD is often associated with the development of asthma and food allergies, which is known as “atopic march” [10]. Physical therapies that moisturize the skin, preventing water loss, controlling xerosis, and relieving barrier disruptions, are recommended for AD patients [11]. While corticosteroids remain the standard anti-inflammatory treatment against AD, the efficacy of blocking TH2 responses is recognized by various clinical trials [12][13][14][15][16][17][18][19]. Unfortunately, the limited armamentarium [20] and the high heterogeneity of the disease [21] make the management of AD challenging. Therefore, novel therapeutic strategies needed for AD treatment.
The past two decades have highlighted the role of commensal microbiota in health homeostasis and disease [22]. As the largest and outmost organ of the body, the human skin has been estimated to host about 1 billion bacteria per 1 cm2 area [23]. Conversely, the gastrointestinal tract harbors the largest microbiota population in the body, exceeding 1014 bacterial cells [24][25]. AD is probably the most well-characterized disease in which skin dysbiosis plays a causal role [6]. In addition, AD is also associated with gut dysbiosis [26]. The investigations from the pre-clinical animal studies and the emerging human 3D skin models furthered the understanding on the complex interplay between the microbiota and the AD context [27][28].

2. The Skin Microbiota Alternation in AD Patients: A Particular Focus on Staphylococcus aureus

It is now well established that changes in the normal skin microbiota composition, a condition known as dysbiosis, contribute to the disruption of cutaneous immune homeostasis and promotes the development of skin diseases, including AD [29][30]. Studies that have demonstrated the association of AD with skin dysbiosis are summarized in Table 1. AD is often accompanied with dysbiosis, featured by increased colonization of staphylococcal species and decreased richness and diversity of other bacterial communities [31]. S. aureus, a dominant species among the family of Staphylococcae, can be 100 times more abundant in AD skin compared to normal healthy skin [32]. On the skin surface, S. aureus secretes virulence factors, including phenol-soluble modulins (PSMs) and proteases, thus disrupting normal skin barrier functions, which alter the epidermal environment favouring the development of AD [33][34][35][36][37]. 
The increased abundance of S. aureus colonization in AD is associated with a depletion in the coagulase-negative staphylococcal species (CoNS), such as S. epidermidis, S. hominis, and other skin commensal bacterial communities, including Streptococcus salivarius, Propionibacterium, Streptococcus, Acinetobacter, Corynebacterium, Prevotella and Proteobacteria [31][38][39][40]. In contrast, these skin commensal microbiota produce antimicrobial substances that inhibit the growth of pathogenic S. aureus and its biofilm formation [30][41][42]. In the non-lesional skin samples of AD patients, CoNS are the dominant bacterial communities [38]. However, their abundances were lower on the skin of healthy individuals compared with non-lesional AD skin [38][43]. This suggests the existence of complex interactions between the different skin microbial communities, which modulate the host’s susceptibility to AD.
Table 1. Summary of the studies demonstrating the dysbiosis of skin microbiota in AD.
Year Subjects, Numbers Methods Results (Alternations of Skin Microbiota) Reference
2012 11 Infants with AD and 12 healthy controls 16S rRNA gene sequencing AD infants: ↓S. salivarius and ↑S. aureus [40]
2012 12 Children with AD and
11 healthy controls		 16S rRNA gene sequencing AD lesion: ↑S. aureus and ↑S. epidermidis [31]
2013 13 AD patients and 49 healthy controls 16S rRNA gene sequencing AD patients: ↑S. aureus, ↓-diversity [44]
2015 21 AD infants and 17 healthy controls Real-time PCR analysis of skin scratches AD infants: ↑S. aureus [45]
2016 128 AD patients (59 young children at 2–12 years, 13 teenagers at 13–17 years, and 56 adults at 18–62 years of age), 68 age-matched healthy controls (13 young children, 10 teenagers, 45 adults) 16S rRNA gene sequencing Children with AD:
↑Streptococcus, ↑Granulicatelle, ↑Gemella, ↑Rothia, ↑Haemophilus
Adults with AD:
↑Propionibacterium, ↑Corynebacterium, ↑Staphylococcus, ↑Lactobacillus, ↑Finegoldia, ↑Anaerococcus		 [46]
2016 Three male first cousins aged 50–53 years 16S rRNA gene sequencing AD patients: ↑S. aureus [47]
2017 10 AD infants, 10 age-matched healthy controls 16S rRNA gene sequencing AD infants: ↑Staphylococcus [29]
2017 49 AD patients and 30 non-AD subjects 16S rRNA gene sequencing AD patients: ↓S. epidermidis, ↓S. hominis [30]
2017 27 AD patients and 6 healthy controls High-throughput pyrosequencing AD patients:
↑Staphylococcus, ↑Pseudomonas, and ↑Streptococcus, ↓Alcaligenaceae (f), ↓Sediminibacterium, and ↓Lactococcus		 [48]
2018 10 AD patients and 10 healthy controls 16S rRNA gene sequencing AD patients: ↑S. aureus, ↓-diversity [38]
2019 91 AD patients, 134 psoriasis patients, and 126 healthy controls 16S rRNA gene sequencing AD patients: ↑S. aureus, ↓S. epidermidis and ↓Corynebacterium [49]
2019 172 AD patients and 120 healthy controls 16S rRNA gene sequencing AD patients: ↑Staphylococcus [50]
2020 11 AD patients 16S rRNA gene sequencing AD skin lesions: ↑S. aureus, ↓C. pseudogenitalium [51]
2020 67 AD patients and 28 healthy controls 16S rRNA gene sequencing AD skin lesion:
↑Staphylococcus (S. aureus and S. epidermidis), ↓Corynebacterium, ↓Micrococcus, ↓Cutibacterium and ↓Streptococcus		 [52]
2020 7 AD patients and 10 healthy controls 16S rRNA gene sequencing, and Staphylococcus specific SLST sequencing AD patients:
↑Staphylococcus, ↓Propionibacterium		 [53]
2021 28 AD patients and 14 healthy controls 16S rRNA gene sequencing AD patients: ↑S. aureus, ↓S. capitis and ↓Micrococcus sp. [54]
Legend: SLST, single-locus sequencing typing.

3. The Gut Microbiota Profiles in AD Patients

Aside from the skin microbiota, the gut microbiota, known to have a systemic impact on the host immune responses, is also closely associated with atopic diseases such as AD. A hypothesis of the “gut-skin” axis has been proposed and has opened new paths related to the prevention and treatment of AD [26]. Numerous studies demonstrated that AD is associated with gut dysbiosis, especially during early life. AD patients display poor gut microbial diversity in several clinical trials [55][56][57][58][59][60][61][62][63], while contradictory results exist [64][65][66][67]. Similarly, to the skin, AD patients exhibit abundant S. aureus in their gut microbiota [68][69][70][71]. Other microbes associated with inflammation and epithelial damage, such as Clostridiodes difficile, and coliforms, including pathogenic Escherichia coli, are increased in the gut microbiota of AD patients [61][65][71][72][73][74][75][76][77]. Metagenomic analysis has shown that the gut microbes in AD patients carry extra genes associated with inflammatory responses and the breakdown of gut epithelial layers [64][66]. Breastfed infants have a lower risk of atopic diseases [78][79][80][81][82][83], likely because of the abundance of Bifidobacteria in their gut [84][85][86][87], a genus that is reduced in the gut microbiota of AD patients [76][88][89][90][91]. However, it has been reported that AD development is also associated with the higher abundance of certain species of Bifidobacteria, such as Bifidobacterium catenulatum, B. bifidum and B. pseudocatenulatum [92][93]. Short-chain fatty acids (SCFAs) are microbial metabolites well known for their anti-inflammatory effects. High fecal levels of SCFAs are significantly associated with a lower risk of AD [64][94]. The SCFA-producing bacteria Coprococcus eutactus is less abundant in the gut microbiota of AD patients [60]. Subspecies of Faecalibacterium prausnitzii are enriched in AD fecal samples. Although F. prausnitzii is a major SCFA producer in healthy subjects, this species is an inefficient SCFA producer in AD patients [64]. Furthermore, genes encoding carbohydrate active enzymes (CAZymes), which break down resistant starch into SCFAs, are deficient in the gut microbiota of AD patients [67]. While infantile gut dysbiosis may predict the development of AD [56][57][59][72][73][74][77], childhood AD history had prolonged imprints in gut microbiota that neonates with childhood AD history had a lower abundance of Bifidobacteria, Akkermansia, and Faecalibacteria compared to their healthy counterparts [95].
Despite these reports linking gut dysbiosis with AD, the actual roles of gut microbiota in AD development are still largely unknown. Establishing a causative role for the gut microbiota in the development of diseases remains challenging. An invaluable tool for this type of investigation is the use of germ-free animals. Germ-free mice showed similar disease severity in the oxazolone-induced ear atopic dermatitis model as conventional mice [96]. However, germ-free mice have higher levels of serum IgE and inflammatory cytokines, such as TNF and IL-6 in ear tissues, suggesting exacerbated skin inflammation [96]. Furthermore, the sensitivity to oxazolone is transferable to germ-free mice with fecal microbiota transplant (FMT) [96]. These findings suggest a causative role of gut microbiota in the development of AD. However, the direct link between gut microbiota and type 2 inflammatory responses in AD is still unknown.

4. The Gut Microbiota Regulates AD-Related Immune Responses and the Underlying Mechanisms

There is firm evidence supporting the role of gut microbiota-regulated immune responses in atopic diseases and AD [97]. For example, early colonization of Bifidobacteria subtly regulates the TH1/TH2 immune balance, reducing the risk of AD [98]. Most of the knowledge regarding this arises from the use of probiotics in different clinical trials, as discussed below. In this section, researchers focus on three aspects: (1) SCFAs-anti-inflammation axis, (2) tryptophan metabolites-AHR axis, and (3) toll-like receptor signalling (Figure 1). These pathways that can be modulated by gut microbiota are well characterized and highly relevant to AD and other allergic immune responses.
Figure 1. Mechanisms of how gut microbiota regulate AD pathogenesis. Short-chain fatty acids (SCFAs) produced by the gut microbiota are able to activate SCFA-sensing G-protein coupled receptors (GPCRs) and/or inhibit histone deacetylases (HDACs), thus activating downstream signalling cascades that suppress inflammatory responses and restoring TH1/TH2 balance. Microbial metabolite, D-tryptophan can also restore TH1/TH2 balance. Bifidobacteria, a genus of bacteria to which many probiotics belong, are an important source of these metabolites. Microbial tryptophan metabolites can activate the aryl hydrocarbon receptor (AHR), which inhibits inflammatory responses and improve the epidermal barrier of skin. Pathogen-associated molecular patterns produced by the gut microbiota can activate toll-like receptors (TLRs) thus restoring TH1/TH2 balance. All these mechanisms benefit AD. IAld, indole-3-aldehyde; IAA, indole-3-acetic acid; IPA, indole-3-propionic acid; TA, tryptamine; ARNT, aryl hydrocarbon receptor nuclear translocator. Created with BioRender.com

This entry is adapted from the peer-reviewed paper 10.3390/pathogens11060642

References

  1. Eichenfield, L.F.; Tom, W.L.; Chamlin, S.L.; Feldman, S.R.; Hanifin, J.M.; Simpson, E.L.; Berger, T.G.; Bergman, J.N.; Cohen, D.E.; Cooper, K.D.; et al. Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis. J. Am. Acad. Dermatol. 2014, 70, 338–351.
  2. Weidinger, S.; Novak, N. Atopic dermatitis. Lancet 2016, 387, 1109–1122.
  3. Bieber, T. Atopic Dermatitis. Ann. Derm. 2010, 22, 125–137.
  4. Deckers, I.A.G.; McLean, S.; Linssen, S.; Mommers, M.; van Schayck, C.P.; Sheikh, A. Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 1990–2010: A Systematic Review of Epidemiological Studies. PLoS ONE 2012, 7, e39803.
  5. Williams, H.; Stewart, A.; von Mutius, E.; Cookson, W.; Anderson, H.R. Is eczema really on the increase worldwide? J. Allergy Clin. Immunol. 2008, 121, 947–954.e15.
  6. Dainichi, T.; Kitoh, A.; Otsuka, A.; Nakajima, S.; Nomura, T.; Kaplan, D.H.; Kabashima, K. The epithelial immune microenvironment (EIME) in atopic dermatitis and psoriasis. Nat. Immunol. 2018, 19, 1286–1298.
  7. Bisgaard, H.; Simpson, A.; Palmer, C.N.; Bonnelykke, K.; McLean, I.; Mukhopadhyay, S.; Pipper, C.B.; Halkjaer, L.B.; Lipworth, B.; Hankinson, J.; et al. Gene-environment interaction in the onset of eczema in infancy: Filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med. 2008, 5, e131.
  8. Palmer, C.N.; Irvine, A.D.; Terron-Kwiatkowski, A.; Zhao, Y.; Liao, H.; Lee, S.P.; Goudie, D.R.; Sandilands, A.; Campbell, L.E.; Smith, F.J.; et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat. Genet. 2006, 38, 441–446.
  9. Sandilands, A.; Terron-Kwiatkowski, A.; Hull, P.R.; O’Regan, G.M.; Clayton, T.H.; Watson, R.M.; Carrick, T.; Evans, A.T.; Liao, H.; Zhao, Y.; et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat. Genet. 2007, 39, 650–654.
  10. Egawa, G.; Kabashima, K. Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to prevent the atopic march. J. Allergy Clin. Immunol. 2016, 138, 350–358.e1.
  11. Eichenfield, L.F.; Tom, W.L.; Berger, T.G.; Krol, A.; Paller, A.S.; Schwarzenberger, K.; Bergman, J.N.; Chamlin, S.L.; Cohen, D.E.; Cooper, K.D.; et al. Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies. J. Am. Acad. Dermatol. 2014, 71, 116–132.
  12. Faiz, S.; Giovannelli, J.; Podevin, C.; Jachiet, M.; Bouaziz, J.-D.; Reguiai, Z.; Nosbaum, A.; Lasek, A.; le Bouedec, M.-C.F.; Du Thanh, A.; et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J. Am. Acad. Dermatol. 2019, 81, 143–151.
  13. Abraham, S.; Haufe, E.; Harder, I.; Heratizadeh, A.; Kleinheinz, A.; Wollenberg, A.; Weisshaar, E.; Augustin, M.; Wiemers, F.; Zink, A.; et al. Implementation of dupilumab in routine care of atopic eczema: Results from the German national registry TREATgermany. Br. J. Derm. 2020, 183, 382–384.
  14. Deleuran, M.; Thaçi, D.; Beck, L.A.; de Bruin-Weller, M.; Blauvelt, A.; Forman, S.; Bissonnette, R.; Reich, K.; Soong, W.; Hussain, I.; et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J. Am. Acad. Dermatol. 2020, 82, 377–388.
  15. Wang, C.; Kraus, C.N.; Patel, K.G.; Ganesan, A.K.; Grando, S.A. Real-world experience of dupilumab treatment for atopic dermatitis in adults: A retrospective analysis of patients’ records. Int. J. Dermatol. 2020, 59, 253–256.
  16. Wollenberg, A.; Blauvelt, A.; Guttman-Yassky, E.; Worm, M.; Lynde, C.; Lacour, J.P.; Spelman, L.; Katoh, N.; Saeki, H.; Poulin, Y.; et al. Tralokinumab for moderate-to-severe atopic dermatitis: Results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Derm. 2021, 184, 437–449.
  17. Popovic, B.; Breed, J.; Rees, D.G.; Gardener, M.J.; Vinall, L.M.; Kemp, B.; Spooner, J.; Keen, J.; Minter, R.; Uddin, F.; et al. Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2. J. Mol. Biol. 2017, 429, 208–219.
  18. He, H.; Guttman-Yassky, E. JAK Inhibitors for Atopic Dermatitis: An Update. Am. J. Clin. Dermatol. 2019, 20, 181–192.
  19. Cotter, D.G.; Schairer, D.; Eichenfield, L. Emerging therapies for atopic dermatitis: JAK inhibitors. J. Am. Acad. Dermatol. 2018, 78, S53–S62.
  20. Bieber, T. Atopic dermatitis: An expanding therapeutic pipeline for a complex disease. Nat. Rev. Drug Discov. 2021, 21, 21–40.
  21. Yew, Y.W.; Thyssen, J.P.; Silverberg, J.I. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J. Am. Acad. Derm. 2019, 80, 390–401.
  22. Ruff, W.E.; Greiling, T.M.; Kriegel, M.A. Host–microbiota interactions in immune-mediated diseases. Nat. Rev. Microbiol. 2020, 18, 521–538.
  23. Grice, E.A.; Kong, H.H.; Renaud, G.; Young, A.C.; Program, N.C.S.; Bouffard, G.G.; Blakesley, R.W.; Wolfsberg, T.G.; Turner, M.L.; Segre, J.A. A diversity profile of the human skin microbiota. Genome Res. 2008, 18, 1043–1050.
  24. Backhed, F.; Ley, R.E.; Sonnenburg, J.L.; Peterson, D.A.; Gordon, J.I. Host-bacterial mutualism in the human intestine. Science 2005, 307, 1915–1920.
  25. Gill, S.R.; Pop, M.; Deboy, R.T.; Eckburg, P.B.; Turnbaugh, P.J.; Samuel, B.S.; Gordon, J.I.; Relman, D.A.; Fraser-Liggett, C.M.; Nelson, K.E. Metagenomic analysis of the human distal gut microbiome. Science 2006, 312, 1355–1359.
  26. Lee, S.Y.; Lee, E.; Park, Y.M.; Hong, S.J. Microbiome in the Gut-Skin Axis in Atopic Dermatitis. Allergy Asthma. Immunol. Res. 2018, 10, 354–362.
  27. Byrd, A.L.; Deming, C.; Cassidy, S.K.B.; Harrison, O.J.; Ng, W.I.; Conlan, S.; Belkaid, Y.; Segre, J.A.; Kong, H.H. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci. Transl. Med. 2017, 9, eaal4651.
  28. Emmert, H.; Rademacher, F.; Gläser, R.; Harder, J. Skin microbiota analysis in human 3D skin models—“Free your mice”. Exp. Dermatol. 2020, 29, 1133–1139.
  29. Kennedy, E.A.; Connolly, J.; Hourihane, J.O.; Fallon, P.G.; McLean, W.H.I.; Murray, D.; Jo, J.H.; Segre, J.A.; Kong, H.H.; Irvine, A.D. Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J. Allergy Clin. Immunol. 2017, 139, 166–172.
  30. Nakatsuji, T.; Chen, T.H.; Narala, S.; Chun, K.A.; Two, A.M.; Yun, T.; Shafiq, F.; Kotol, P.F.; Bouslimani, A.; Melnik, A.V.; et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci. Transl. Med. 2017, 9, eaah4680.
  31. Kong, H.H.; Oh, J.; Deming, C.; Conlan, S.; Grice, E.A.; Beatson, M.A.; Nomicos, E.; Polley, E.C.; Komarow, H.D.; Murray, P.R.; et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012, 22, 850–859.
  32. Williams, M.R.; Nakatsuji, T.; Gallo, R.L. Staphylococcus aureus: Master Manipulator of the Skin. Cell Host Microbe 2017, 22, 579–581.
  33. Hirasawa, Y.; Takai, T.; Nakamura, T.; Mitsuishi, K.; Gunawan, H.; Suto, H.; Ogawa, T.; Wang, X.-L.; Ikeda, S.; Okumura, K.; et al. Staphylococcus aureus Extracellular Protease Causes Epidermal Barrier Dysfunction. J. Investig. Dermatol. 2010, 130, 614–617.
  34. Leung, D.Y. Infection in atopic dermatitis. Curr. Opin. Pediatr. 2003, 15, 399–404.
  35. Maintz, L.; Novak, N. Modifications of the innate immune system in atopic dermatitis. J. Innate Immun. 2011, 3, 131–141.
  36. Nakagawa, S.; Matsumoto, M.; Katayama, Y.; Oguma, R.; Wakabayashi, S.; Nygaard, T.; Saijo, S.; Inohara, N.; Otto, M.; Matsue, H.; et al. Staphylococcus aureus Virulent PSMalpha Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation. Cell Host Microbe 2017, 22, 667–677.e5.
  37. Williams, M.R.; Nakatsuji, T.; Sanford, J.A.; Vrbanac, A.F.; Gallo, R.L. Staphylococcus aureus Induces Increased Serine Protease Activity in Keratinocytes. J. Investig. Dermatol. 2017, 137, 377–384.
  38. Baurecht, H.; Ruhlemann, M.C.; Rodriguez, E.; Thielking, F.; Harder, I.; Erkens, A.S.; Stolzl, D.; Ellinghaus, E.; Hotze, M.; Lieb, W.; et al. Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration. J. Allergy Clin. Immunol. 2018, 141, 1668–1676.e16.
  39. Lunjani, N.; Hlela, C.; O’Mahony, L. Microbiome and skin biology. Curr. Opin. Allergy Clin. Immunol. 2019, 19, 328–333.
  40. Glatz, M.; Jo, J.H.; Kennedy, E.A.; Polley, E.C.; Segre, J.A.; Simpson, E.L.; Kong, H.H. Emollient use alters skin barrier and microbes in infants at risk for developing atopic dermatitis. PLoS ONE 2018, 13, e0192443.
  41. Iwase, T.; Uehara, Y.; Shinji, H.; Tajima, A.; Seo, H.; Takada, K.; Agata, T.; Mizunoe, Y. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 2010, 465, 346–349.
  42. Kaci, G.; Goudercourt, D.; Dennin, V.; Pot, B.; Doré, J.; Ehrlich, S.D.; Renault, P.; Blottière, H.M.; Daniel, C.; Delorme, C. Anti-inflammatory properties of Streptococcus salivarius, a commensal bacterium of the oral cavity and digestive tract. Appl. Environ. Microbiol. 2014, 80, 928–934.
  43. Clausen, M.L.; Agner, T.; Lilje, B.; Edslev, S.M.; Johannesen, T.B.; Andersen, P.S. Association of Disease Severity with Skin Microbiome and Filaggrin Gene Mutations in Adult Atopic Dermatitis. JAMA Derm. 2018, 154, 293–300.
  44. Oh, J.; Freeman, A.F.; Program, N.C.S.; Park, M.; Sokolic, R.; Candotti, F.; Holland, S.M.; Segre, J.A.; Kong, H.H. The altered landscape of the human skin microbiome in patients with primary immunodeficiencies. Genome Res. 2013, 23, 2103–2114.
  45. Laborel-Preneron, E.; Bianchi, P.; Boralevi, F.; Lehours, P.; Fraysse, F.; Morice-Picard, F.; Sugai, M.; Sato’o, Y.; Badiou, C.; Lina, G.; et al. Effects of the Staphylococcus aureus and Staphylococcus epidermidis Secretomes Isolated from the Skin Microbiota of Atopic Children on CD4+ T Cell Activation. PLoS ONE 2015, 10, e0141067.
  46. Shi, B.; Bangayan, N.J.; Curd, E.; Taylor, P.A.; Gallo, R.L.; Leung, D.Y.M.; Li, H. The skin microbiome is different in pediatric versus adult atopic dermatitis. J. Allergy Clin. Immunol. 2016, 138, 1233–1236.
  47. Drago, L.; De Grandi, R.; Altomare, G.; Pigatto, P.; Rossi, O.; Toscano, M. Skin microbiota of first cousins affected by psoriasis and atopic dermatitis. Clin. Mol. Allergy 2016, 14, 2.
  48. Kim, M.H.; Rho, M.; Choi, J.P.; Choi, H.I.; Park, H.K.; Song, W.J.; Min, T.K.; Cho, S.H.; Cho, Y.J.; Kim, Y.K.; et al. A Metagenomic Analysis Provides a Culture-Independent Pathogen Detection for Atopic Dermatitis. Allergy Asthma Immunol. Res. 2017, 9, 453–461.
  49. Fyhrquist, N.; Muirhead, G.; Prast-Nielsen, S.; Jeanmougin, M.; Olah, P.; Skoog, T.; Jules-Clement, G.; Feld, M.; Barrientos-Somarribas, M.; Sinkko, H.; et al. Microbe-host interplay in atopic dermatitis and psoriasis. Nat. Commun. 2019, 10, 4703.
  50. Li, W.; Xu, X.; Wen, H.; Wang, Z.; Ding, C.; Liu, X.; Gao, Y.; Su, H.; Zhang, J.; Han, Y.; et al. Inverse Association Between the Skin and Oral Microbiota in Atopic Dermatitis. J. Investig. Derm. 2019, 139, 1779–1787.e12.
  51. Capone, K.; Kirchner, F.; Klein, S.L.; Tierney, N.K. Effects of Colloidal Oatmeal Topical Atopic Dermatitis Cream on Skin Microbiome and Skin Barrier Properties. J. Drugs Derm. 2020, 19, 524–531.
  52. Xu, Z.; Liu, X.; Niu, Y.; Shen, C.; Heminger, K.; Moulton, L.; Yu, A.; Allen, T.; Zhang, L.; Yue, F.; et al. Skin benefits of moisturising body wash formulas for children with atopic dermatitis: A randomised controlled clinical study in China. Australas J. Derm. 2020, 61, e54–e59.
  53. Smits, J.P.H.; Ederveen, T.H.A.; Rikken, G.; van den Brink, N.J.M.; van Vlijmen-Willems, I.; Boekhorst, J.; Kamsteeg, M.; Schalkwijk, J.; van Hijum, S.; Zeeuwen, P.; et al. Targeting the Cutaneous Microbiota in Atopic Dermatitis by Coal Tar via AHR-Dependent Induction of Antimicrobial Peptides. J. Investig. Derm. 2020, 140, 415–424.e10.
  54. Khadka, V.D.; Key, F.M.; Romo-Gonzalez, C.; Martinez-Gayosso, A.; Campos-Cabrera, B.L.; Geronimo-Gallegos, A.; Lynn, T.C.; Duran-McKinster, C.; Coria-Jimenez, R.; Lieberman, T.D.; et al. The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment. Front. Cell. Infect. Microbiol. 2021, 11, 720674.
  55. Forno, E.; Onderdonk, A.B.; McCracken, J.; Litonjua, A.A.; Laskey, D.; Delaney, M.L.; DuBois, A.M.; Gold, D.R.; Ryan, L.M.; Weiss, S.T.; et al. Diversity of the gut microbiota and eczema in early life. Clin. Mol. Allergy 2008, 6, 11.
  56. Wang, M.; Karlsson, C.; Olsson, C.; Adlerberth, I.; Wold, A.E.; Strachan, D.P.; Martricardi, P.M.; Åberg, N.; Perkin, M.R.; Tripodi, S.; et al. Reduced diversity in the early fecal microbiota of infants with atopic eczema. J. Allergy Clin. Immunol. 2008, 121, 129–134.
  57. Bisgaard, H.; Li, N.; Bonnelykke, K.; Chawes, B.L.K.; Skov, T.; Paludan-Müller, G.; Stokholm, J.; Smith, B.; Krogfelt, K.A. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. J. Allergy Clin. Immunol. 2011, 128, 646–652.e5.
  58. Abrahamsson, T.R.; Jakobsson, H.E.; Andersson, A.F.; Björkstén, B.; Engstrand, L.; Jenmalm, M.C. Low diversity of the gut microbiota in infants with atopic eczema. J. Allergy Clin. Immunol. 2012, 129, 434–440.e2.
  59. Ismail, I.H.; Oppedisano, F.; Joseph, S.J.; Boyle, R.J.; Licciardi, P.V.; Robins-Browne, R.M.; Tang, M.L.K. Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Pediatr. Allergy Immunol. 2012, 23, 674–681.
  60. Nylund, L.; Nermes, M.; Isolauri, E.; Salminen, S.; de Vos, W.M.; Satokari, R. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria. Allergy 2015, 70, 241–244.
  61. Zimmermann, P.; Messina, N.; Mohn, W.W.; Finlay, B.B.; Curtis, N. Association between the intestinal microbiota and allergic sensitization, eczema, and asthma: A systematic review. J. Allergy Clin. Immunol. 2019, 143, 467–485.
  62. Ye, S.; Yan, F.; Wang, H.; Mo, X.; Liu, J.; Zhang, Y.; Li, H.; Chen, D. Diversity analysis of gut microbiota between healthy controls and those with atopic dermatitis in a Chinese population. J. Dermatol. 2021, 48, 158–167.
  63. Hu, C.; van Meel, E.R.; Medina-Gomez, C.; Kraaij, R.; Barroso, M.; Kiefte-de Jong, J.; Radjabzadeh, D.; Pasmans, S.G.M.A.; de Jong, N.W.; de Jongste, J.C.; et al. A population-based study on associations of stool microbiota with atopic diseases in school-age children. J. Allergy Clin. Immunol. 2021, 148, 612–620.
  64. Song, H.; Yoo, Y.; Hwang, J.; Na, Y.-C.; Kim, H.S. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J. Allergy Clin. Immunol. 2016, 137, 852–860.
  65. Wang, H.; Li, Y.; Feng, X.; Li, Y.; Wang, W.; Qiu, C.; Xu, J.; Yang, Z.; Li, Z.; Zhou, Q.; et al. Dysfunctional gut microbiota and relative co-abundance network in infantile eczema. Gut Pathog. 2016, 8, 36.
  66. Lee, M.-J.; Kang, M.-J.; Lee, S.-Y.; Lee, E.; Kim, K.; Won, S.; Suh, D.I.; Kim, K.W.; Sheen, Y.H.; Ahn, K.; et al. Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type. J. Allergy Clin. Immunol. 2018, 141, 1310–1319.
  67. Cait, A.; Cardenas, E.; Dimitriu, P.A.; Amenyogbe, N.; Dai, D.; Cait, J.; Sbihi, H.; Stiemsma, L.; Subbarao, P.; Mandhane, P.J.; et al. Reduced genetic potential for butyrate fermentation in the gut microbiome of infants who develop allergic sensitization. J. Allergy Clin. Immunol. 2019, 144, 1638–1647.e3.
  68. Björkstén, B.; Naaber, P.; Sepp, E.; Mikelsaar, M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin. Exp. Allergy 1999, 29, 342–346.
  69. Björkstén, B.; Sepp, E.; Julge, K.; Voor, T.; Mikelsaar, M. Allergy development and the intestinal microflora during the first year of life. J. Allergy Clin. Immunol. 2001, 108, 516–520.
  70. Adlerberth, I.; Strachan, D.P.; Matricardi, P.M.; Ahrné, S.; Orfei, L.; Åberg, N.; Perkin, M.R.; Tripodi, S.; Hesselmar, B.; Saalman, R.; et al. Gut microbiota and development of atopic eczema in 3 European birth cohorts. J. Allergy Clin. Immunol. 2007, 120, 343–350.
  71. Melli, L.C.F.L.; do Carmo-Rodrigues, M.S.; Araújo-Filho, H.B.; Mello, C.S.; Tahan, S.; Pignatari, A.C.C.; Solé, D.; de Morais, M.B. Gut microbiota of children with atopic dermatitis: Controlled study in the metropolitan region of São Paulo, Brazil. Allergol. Immunopathol. 2020, 48, 107–115.
  72. Penders, J.; Stobberingh, E.E.; Thijs, C.; Adams, H.; Vink, C.; Van Ree, R.; Van Den Brandt, P.A. Molecular fingerprinting of the intestinal microbiota of infants in whom atopic eczema was or was not developing. Clin. Exp. Allergy 2006, 36, 1602–1608.
  73. Penders, J.; Thijs, C.; van den Brandt, P.A.; Kummeling, I.; Snijders, B.; Stelma, F.; Adams, H.; van Ree, R.; Stobberingh, E.E. Gut microbiota composition and development of atopic manifestations in infancy: The KOALA Birth Cohort Study. Gut 2007, 56, 661.
  74. van Nimwegen, F.A.; Penders, J.; Stobberingh, E.E.; Postma, D.S.; Koppelman, G.H.; Kerkhof, M.; Reijmerink, N.E.; Dompeling, E.; van den Brandt, P.A.; Ferreira, I.; et al. Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J. Allergy Clin. Immunol. 2011, 128, 948–955.e3.
  75. Penders, J.; Gerhold, K.; Stobberingh, E.E.; Thijs, C.; Zimmermann, K.; Lau, S.; Hamelmann, E. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J. Allergy Clin. Immunol. 2013, 132, 601–607.e8.
  76. Zheng, H.; Liang, H.; Wang, Y.; Miao, M.; Shi, T.; Yang, F.; Liu, E.; Yuan, W.; Ji, Z.-S.; Li, D.-K. Altered Gut Microbiota Composition Associated with Eczema in Infants. PLoS ONE 2016, 11, e0166026.
  77. Lee, E.; Lee, S.-Y.; Kang, M.-J.; Kim, K.; Won, S.; Kim, B.-J.; Choi, K.Y.; Kim, B.-S.; Cho, H.-J.; Kim, Y.; et al. Clostridia in the gut and onset of atopic dermatitis via eosinophilic inflammation. Ann. Allergy Asthma Immunol. 2016, 117, 91–92.e1.
  78. Kull, I.; Böhme, M.; Wahlgren, C.F.; Nordvall, L.; Pershagen, G.; Wickman, M. Breast-feeding reduces the risk for childhood eczema. J. Allergy Clin. Immunol. 2005, 116, 657–661.
  79. Ehlayel, M.S.; Bener, A. Duration of breast-feeding and the risk of childhood allergic diseases in a developing country. Allergy Asthma Proc. 2008, 29, 386–391.
  80. Chiu, C.Y.; Liao, S.L.; Su, K.W.; Tsai, M.H.; Hua, M.C.; Lai, S.H.; Chen, L.C.; Yao, T.C.; Yeh, K.W.; Huang, J.L. Exclusive or Partial Breastfeeding for 6 Months Is Associated With Reduced Milk Sensitization and Risk of Eczema in Early Childhood: The PATCH Birth Cohort Study. Medicine 2016, 95, e3391.
  81. Gdalevich, M.; Mimouni, D.; David, M.; Mimouni, M. Breast-feeding and the onset of atopic dermatitis in childhood: A systematic review and meta-analysis of prospective studies. J. Am. Acad. Derm. 2001, 45, 520–527.
  82. Schoetzau, A.; Filipiak-Pittroff, B.; Franke, K.; Koletzko, S.; Von Berg, A.; Gruebl, A.; Bauer, C.P.; Berdel, D.; Reinhardt, D.; Wichmann, H.E. Effect of exclusive breast-feeding and early solid food avoidance on the incidence of atopic dermatitis in high-risk infants at 1 year of age. Pediatr. Allergy Immunol. 2002, 13, 234–242.
  83. Flohr, C.; Nagel, G.; Weinmayr, G.; Kleiner, A.; Strachan, D.P.; Williams, H.C. Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: Lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two. Br. J. Derm. 2011, 165, 1280–1289.
  84. Escherich, T. Die Darmbakterien des Säuglings und Ihre Beziehungen zur Physiologie der Verdauung; F. Enke: Stuttgart, Germany, 1886.
  85. Moro, E. Morphologie und bakteriologische Untersuchungen über die Darmbakterien des Säuglings: Die Bakterien-flora des normalen Frauenmilchstuhls. Jahrb. Kinderh 1900, 61, 686–734.
  86. Tissier, H. Recherches sur la Flore Intestinale des Nourrissons: (état Normal et Pathologique). Ph.D. Thesis, University of Paris, Paris, France, 1900.
  87. Harmsen, H.J.; Wildeboer-Veloo, A.C.; Raangs, G.C.; Wagendorp, A.A.; Klijn, N.; Bindels, J.G.; Welling, G.W. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J. Pediatr. Gastroenterol. Nutr. 2000, 30, 61–67.
  88. Kalliomäki, M.; Kirjavainen, P.; Eerola, E.; Kero, P.; Salminen, S.; Isolauri, E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J. Allergy Clin. Immunol. 2001, 107, 129–134.
  89. Watanabe, S.; Narisawa, Y.; Arase, S.; Okamatsu, H.; Ikenaga, T.; Tajiri, Y.; Kumemura, M. Differences in fecal microflora between patients with atopic dermatitis and healthy control subjects. J. Allergy Clin. Immunol. 2003, 111, 587–591.
  90. Mah, K.W.; Björkstén, B.; Lee, B.W.; van Bever, H.P.; Shek, L.P.; Tan, T.N.; Lee, Y.K.; Chua, K.Y. Distinct Pattern of Commensal Gut Microbiota in Toddlers with Eczema. Int. Arch. Allergy Immunol. 2006, 140, 157–163.
  91. Hong, P.-Y.; Lee, B.W.; Aw, M.; Shek, L.P.C.; Yap, G.C.; Chua, K.Y.; Liu, W.-T. Comparative Analysis of Fecal Microbiota in Infants with and without Eczema. PLoS ONE 2010, 5, e9964.
  92. Suzuki, S.; Shimojo, N.; Tajiri, Y.; Kumemura, M.; Kohno, Y. Differences in the composition of intestinal Bifidobacterium species and the development of allergic diseases in infants in rural Japan. Clin. Exp. Allergy 2007, 37, 506–511.
  93. Gore, C.; Munro, K.; Lay, C.; Bibiloni, R.; Morris, J.; Woodcock, A.; Custovic, A.; Tannock, G.W. Bifidobacterium pseudocatenulatum is associated with atopic eczema: A nested case-control study investigating the fecal microbiota of infants. J. Allergy Clin. Immunol. 2008, 121, 135–140.
  94. Roduit, C.; Frei, R.; Ferstl, R.; Loeliger, S.; Westermann, P.; Rhyner, C.; Schiavi, E.; Barcik, W.; Rodriguez-Perez, N.; Wawrzyniak, M.; et al. High levels of butyrate and propionate in early life are associated with protection against atopy. Allergy 2019, 74, 799–809.
  95. Fujimura, K.E.; Sitarik, A.R.; Havstad, S.; Lin, D.L.; Levan, S.; Fadrosh, D.; Panzer, A.R.; LaMere, B.; Rackaityte, E.; Lukacs, N.W.; et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 2016, 22, 1187–1191.
  96. Zachariassen, L.F.; Krych, L.; Engkilde, K.; Nielsen, D.S.; Kot, W.; Hansen, C.H.F.; Hansen, A.K. Sensitivity to oxazolone induced dermatitis is transferable with gut microbiota in mice. Sci. Rep. 2017, 7, 44385.
  97. McKenzie, C.; Tan, J.; Macia, L.; Mackay, C.R. The nutrition-gut microbiome-physiology axis and allergic diseases. Immunol. Rev. 2017, 278, 277–295.
  98. Sestito, S.; D’Auria, E.; Baldassarre, M.E.; Salvatore, S.; Tallarico, V.; Stefanelli, E.; Tarsitano, F.; Concolino, D.; Pensabene, L. The Role of Prebiotics and Probiotics in Prevention of Allergic Diseases in Infants. Front. Pediatr. 2020, 8, 583946.
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