Microbiota cutaneo


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Analisi del microbiota cutaneo nella cute sana e nella dermatite atopica

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Microbiota cutaneo

  1. 1. L’ecosistema cutaneo nell ’eczema 12 - 14 Settembre 2013 Dr. G. Baviera
  2. 2. TEATRO OPERATIVO • CUTE: 2.5 m2 • APPARATO RESPIRATORIO: 150 m2 • APPARATO DIGERENTE: 400 m2 Lungo queste superfici ciascuno di noi ospita circa 100 trilioni di batteri che corrispondono all’ 1–3% del peso corporeo
  3. 3. J.I.D. 2012;132:934 La cute è una interfaccia con l’ambiente esterno ma anche un ecosistema composto di diversi habitats ricchi di tasche, invaginazioni e nicchie specializzate che ospitano una ampia variabilità di virus, batteri, funghi, acari
  4. 4. CUTE COME ECOSISTEMA Le varie regioni cutanee hanno differenti popolazioni microbiche residenti che riflettono diverse nicchie biologiche. Le conte coloniche di Batteri Aerobi prelevati da aree umide come le ascelle o le pieghe interdigitali dei piedi possono raggiungere 107 batteri per cm2, mentre le aree asciutte come l’avambraccio o il tronco possono ospitare 102 o meno batteri per cm2 Batteri Anaerobi sono presenti sulla cute con conte coloniche di oltre 107 batteri per cm2 (Leyden J.J. J- Invest Dermatol 1987;88:65s) DIVERSI FATTORI ESTERNI POSSONO ALTERARE L’ECOSISTEMA CUTANEO Fattori Ambientali includono temperatura, umidità, salinità, esposizione alla luce Fattori Individuali includono età, sesso, stato immune, condizioni igieniche, uso di farmaci (antibiotici, steroidi), uso di saponi e cosmetici, permanenza in ambiente ospedaliero, presenza di traumi o ustioni. (Roth RR.- Annu Rev Microbiol 1988;42:441-8)
  5. 5. “If microbes were capable of emotion, they would celebrate each time an infant was born. At birth, a new potential host emerges from the protected environment of the uterus, providing pristine surfaces and body cavities as sites for microbial colonization.” G. W. Tanock
  6. 6. Vaginally delivered infants acquired bacterial communities resembling their own mother’s vaginal microbiota. (Lactobacillus, Prevotella) In C-section babies, the lack of a vaginal exposure leads to first microbial communities resembling the human skin microbiota, with an abundance of Staphylococcus spp, Corynebacterium, Propionibacterium spp Dominguez-Bello M. G. PNAS 2010;107(26);11971
  7. 7. Gosalbes M.J. CEA 2013;43:198 Two distinct types of microbiota composition can be detected in meconium samples. Type A - The family Enterobacteriaceae as the most abundant bacterial taxon (58.69%), mainly represented by the Escherichia/Shigella genus (24.68%). Type B – presents Firmicutes, and particularly Lactic Acid Bacteria of the families Leuconostocaceae, Enterococcaceae and Streptococcaceae, with Leuconostoc (25.86%), Enterococcus (16.79%), Lactococcus (14.01%), Staphylococcus (6.75%) or Streptococcus (6.34%) as the most abundant genera High abundances of Escherichia coli and other enterics have been linked to eczema A protective role against atopy has been reported for Lactic Acid Bacteria
  8. 8. LOCAL FACTORS INFLUENCING SKIN COLONIZATION Eccrine glands - Are found on virtually all skin surfaces and continuously bathe the skin surface with their secretion, which is composed mainly of water and salt, but they produce DERMICIDIN. Apocrine glands - located in the axillary vault (armpit), nipple and genitoanal regions, respond to adrenaline by producing milky, viscous, odourless secretions (pheromones ) Sebaceous glands - connected to the hair follicle, secrete the sebum. They support the growth of facultative anaerobes such as Propionibacterium acnes which hydrolyses the triglycerides present in sebum, releasing free fatty acids onto the skin contributing to the acidic pH (~5) and they produce LL37, HBD-2
  9. 9. TOPOGRAFIA CUTANEA MOIST Staphylococcus Corynebacterium OIL Propionibacterium DRY Gram- Mixed phyla
  10. 10. Interpersonal variation of the skin microbiome Skin microbiota from four healthy volunteers (HV1, HV2, HV3, HV4). Similarities of skin microbial communities are more dependent on the site than the individual antecubital crease back nare plantar heel
  11. 11. Fierer N. PNAS 2008;105:17994 % di sequenze per sesso e ore dopo il lavaggio PRENDERE FIGURE SUPPLEMENTARI – FARE 2-3 DIAPO?  There was a core set of bacterial taxa commonly found on the palm surface  Thre is a pronounced intra- and interpersonal variation in bacterial community composition  Hands from the same individual shared only 17% of their phylotypes indicating that there is an enormous amount of heterogeneity within an individual  Only 13% of the bacterial phylotypes on the palm surface are shared between any two individuals  Women had significantly higher diversity than men and the palms of women were also found to harbor significantly greater bacterial diversity than those of men  Community composition was significantly affected by handedness, time since last hand washing, and an individual’s sex
  12. 12. Verhuls N. O. Plos One 2011;6 (12)e28991 Individuals that are highly attractive to An. gambiae s.s. have a significantly higher abundance, but lower diversity of bacteria on their skin than individuals that are poorly attractive PA ------ HA
  13. 13. Fierer N. PNAS 2010;107(14):6477 Fingertips of an individual harbor bacterial communities more similar to those found on the keys of that individual’s keyboard than to those communities found on keyboard keys not touched by the individual Match between bacterial communities on individual keyboards and the fingers of the owners of the keyboards The collective genomes of our microbial symbionts may be more personally identifying than our own human genomes and the structure of these communities can be used to differentiate objects handled by different individuals, even if those objects have been left untouched for up to 2 weeks at room temperature
  14. 14. Nat. Rev. Immunol. 2009;9:687 Ecosistema cutaneo e immunità But our skin’s innate immune system is not solely of human origin
  15. 15. Naik S. Science 2012;337:1115 Significant reduction in IFN- and IL-17A production by T cells, and IL-17A by low Tcells, in skin tissue of GF mice relative to SPF mice The frequency and absolute numbers of cutaneous Foxp3+ Tregs were increased in the absence of commensals Belkaid in 2012 discovered that mice raised in sterile chambers, lacking bacteria on the skin, in the gut and elsewhere, were unable to fight off the parasite Leishmania major. However, if the germ-free mice were inoculated with Staphylococcus epidermidis at the same time as the L. major infection, they were able to defeat the parasite. S. epidermidis interacts with T cells in the skin to produce inflammatory molecules that are central to the immune response
  16. 16. Phenol-soluble modulins produced by a normal microbial resident of human skin, Staph. epidermidis disrupt artificial membrane vesicles and selectively kill skin pathogens Cogen A. L. JID. 2010;130:192
  17. 17. Staphylococcus epidermidis promote innate immunity Gallo R.L., J. Inv. Derm. 2011;131:1974 Staphylococcus epidermidis acts as a barrier against colonization of potentially pathogenic microbes and against overgrowth of already present opportunistic pathogens.
  18. 18. Factors contributing to variation in the skin microbiome
  20. 20. DERMATITE ATOPICA • Now affects 15-20% (previously about 5%) • 20-40% have an innate genetic filaggrin mutation – Decrease “Natural Moisturizing Factors” – Increase skin permeability – Increase pH – Increase risks of IgE sensitization CAN’T KEEP OUT THE MICROBES
  21. 21. The number of children suffering from eczema has tripled in industrialized nations in the past 30 years, suggesting an environmental trigger. More than 90% of AD patients are colonized with S. aureus on both lesional and non-lesional skin, compared with <5% of healthy individuals S. aureus on the AD skin can secrete various exotoxins which are superantigens They may penetrate the skin barrier and contribute to the persistence and exacerbation of allergic skin inflammation No specific link has been identified between virulence factors expressed by S. aureus and flare-ups in patients with AD However…. Microbiota cutaneo ed eczema Grice, E. A. & Segre, J. A. Nature Rev. Microbiol. 9, 244–253 (2011)
  22. 22. Terada M. PNAS 2006;103(23):8816–8821 This raises the intriguing possibility that skin microbial fluctuations modulate the gene–environment interaction on the skin surface, resulting in the episodic exacerbations of AD. In a mouse model that has reduced skin barrier function (the NC/Nga strain, which is deficient in ceramide production), application of Staphylococcus protein A along with an agitating detergent resulted in a severe AD-like phenotype
  23. 23. Nat. Rev. Immunol. 2009;9:687
  24. 24. Mechanisms that promote the increase of S. aureus colonization • Skin barrier dysfunction • Increased synthesis of the extracellular matrix adhesins for S. aureus • Reduced skin lipid content • Changes in the skin surface pH values toward alkalinity • Decreased production of endogenous antimicrobial peptides.
  25. 25. AD skin Nomura I. J Immunol 2003; 171:3262-3269 S. Aureus IL PERCHE’ DI UNA INVASIONE Normal skin
  26. 26. Kong H. H. Genome Res. 2012;22:850 Shifting Microbiomes in AD Temporal shifs in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis
  27. 27. Genome Research H. H. Kong, 2012 22: 850
  28. 28. van den Akker. JID 2006;194:814 From 4 known functional GR gene polymorphisms, homozygous presence of haplotype 3 conferred a 68% lower risk of persistent S. aureus nasal carriage, whereas the combination of the haplotype 5 and the haplotype 1 allele was significantly associated with an 80% increased risk of S. aureus nasal carriage Three human nasal S. aureus carriage patterns can be distinguished: persistent carriage, intermittent carriage, and noncarriage .
  29. 29. A first positive culture for S aureus at age 6 months was associated with AD prevalence in the first and second years of life aOR, 2.13 and aOR, 2.88, respectively and also with severity (aOR, 3.27). Moreover, frequent colonization in the first year of life (2 times) held a 4.29-fold the risk of moderate to severe AD in the second year of life.
  30. 30. Iwase T. NATURE| Vol 465|20 May 2010
  31. 31. Lew L. C., Journal of Applied Microbiology ISSN 1364-5072 Bioactives from probiotics for dermal health: functions and benefits