microbiota cutaneo

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Analisi del microbiota cutaneo nella cute sana e nella dermatite atopica

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  • 1. Lecosistema cutaneo nell eczema 12 - 14 Settembre 2013 Dr. G. Baviera

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 13% del peso corporeo 3. J.I.D. 2012;132:934 La cute una interfaccia con lambiente esterno ma anche un ecosistema composto di diversi habitats ricchi di tasche, invaginazioni e nicchie specializzate che ospitano una ampia variabilit di virus, batteri, funghi, acari 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 lavambraccio 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 LECOSISTEMA CUTANEO Fattori Ambientali includono temperatura, umidit, salinit, esposizione alla luce Fattori Individuali includono et, 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. 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. Vaginally delivered infants acquired bacterial communities resembling their own mothers 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. 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. 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. TOPOGRAFIA CUTANEA MOIST Staphylococcus Corynebacterium OIL Propionibacterium DRY Gram- Mixed phyla 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. 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 individuals sex 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. Fierer N. PNAS 2010;107(14):6477 Fingertips of an individual harbor bacterial communities more similar to those found on the keys of that individuals 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. Nat. Rev. Immunol. 2009;9:687 Ecosistema cutaneo e immunit But our skins innate immune system is not solely of human origin 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. 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. 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. Factors contributing to variation in the skin microbiome 19. DERMATITE ATOPICA 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 CANT KEEP OUT THE MICROBES 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

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