Gene-Environment Interaction in Chronic Inflammatory Disease
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1 Gene-Environment Interaction in Chronic Inflammatory Disease Renz H, von Mutius E, et al. Nature Immunology 2011;12: Renz H, Autenrieth IB, Brandtzeag P, Cookson WO, Holgate S, von Mutius E, et al. JACI 2011;128(6):25-49.
2 Pre- and postnatal environment opportunity for early immuno-education and programming
3 Distribution of bacterial phyla at different anatomical sites Cho and Blaser Nat Rev Genetics 2012;13:260-70
4 Microbe host interaction and immuno-programming environmental microbiota inhalation barrier microbiome respiratory colonisation environmental microbial exposure - diversity - dose - time oral intestinal microbiome vaginal microbiome cutaneous microbiome Figure 3
5 Abrupt shifts in commensal microbiota correspond with changes in diet and health breast milk start fever formula and table foods rice cereal amoxicillin cefdinir cow milk and full adult diet breast milk and formula end Koenig, Spor, Scalfone, Fricker, Stombaugh, Knight, Angenent, Ley. Proc Natl Acad Sci USA 2011;108 Suppl 1:
6 Garn H, Neves JF, Blumberg RS, Renz H. JACI 2013;131(6): diversity; # of OTUs Impact of barrier microbes on organ-based inflammation Maternal Factors allergic phenotype (intestinal) colonization mode of delivery breast feeding healthy? allergic reduced diversity dysbiosis early in life (0 ~ 6 mths) preceeds cause-effect relationship? Sensitization (Th2) Eczema Food allergy Allergic rhinitis / asthma (+) (+) (+/-) (?) birth infancy childhood
7 Altered microbiome preceeds development of allergic phenotypes Reduced diversity/ altered composition at 1 month Phenotype Eczema Assessed at 2 years Abrahamsson et al. JACI 2012;129: day 7 Eczema 12 months Ismail et al. PAI 2012; 23: week Eczema 18 months Wang et al. JACI 2008; 121: week / 12 months 3 weeks IgE, eos., rhinitis; not asthma, eczema asthma up to 6 years Bisgaard et al. JACI 2011; 128: Vael et al. BMC Microbiol 2011; 11:68.
8 Disturbed distribution of bacterial airway colonization in children with difficult asthma Asthma - BAL fluids - children with difficult asthma vs. controls - no infections; no antibiotics Control Hilti et al, Plos one, 2010
9 Mild asthma and microbiota induced sputum l6s rrna Marri et al, JACI 2013
10 Asthma associated microbiota in induced sputum Marri et al, JACI 2013
11 Bacterial taxonomic classifications in the AD skin microbiome. Heidi H. Kong et al. Genome Res. 2012;22: Flare 2012, Published by Cold Spring Harbor Laboratory Press
12 Temporal shifts in skin microbiome associated with disease activity AD microbiome progression hypothesis. Heidi H. Kong et al. Genome Res. 2012;22: , Published by Cold Spring Harbor Laboratory Press
13 Gut colonization with clostridium cluster I at week 5 determines development of AD non-colonized colonized Penders et al, JACI 2013
14 Microbial metabolites impact host response Short chain fatty acids Polysaccharide Peptidoglycane Trimethyl-amin-n-oxide 4-ethylphenol (sulfate) Dorrestein, Mazmanian, Knight, Immunity 2014
15 Metabolites produced by commensal microbiota promote T-reg generation starch fermentation Clostridia SCFA (butyrate, propionate) histone deacytylase (HDAC) H3 acetylation Foxp3-Treg (colon) Arpaia et al, Nature 2013
16 Short chain fatty acids and gut homeostasis Thorburn, Macia, Mackay, Immunity 2014
17 Tryptophan Microbes Immunity Aryl hydrocarbon receptor Thorburn, Macia, Mackay, Immunity, 2014
18 TLR-5 KO develop obesity Vijay-Kumar et al., Science 2010;328:
19 Caesarean delivery: Allergy and asthma risk Medline studies Bager et al, Clin Exp Allergy, 2009
20 Diversity of mother s body habitats Dominguez-Bello et al; PNAS 2010
21 Delivery microbiota asthma and atopy at 1 month Clostridium difficile n = vaginal a mediation analysis b at 6/7 years n = 384 Mode & Place of delivery c Allergic manifestations home vs. hospital eczema, wheeze, asthma n = 2733 KOALA study, van Nimwegen et al, JACI 2011
22 Placental microbial DNA Aagaard et al, Am J Obstetrics and Gynaecology 2013
23 Biodiversity Hannah Whitaker for The New York Times. Prop stylist: Emily Mullin.
24 Traditional farming and early immuno-education Courtesy: Erika von Mutius ALEX-Study ( ) EU-6FWP PASTURE ( ) EU-7FWP PRO-IMMUNE ( )
25 Inverse relationship between microbial exposure and probability of asthma A - Bacteria B - Fungi Living on a farm Asthma Ege et al., NEJM, 2011
26 Microbial diversity and asthma protection one single protective pathway convergence into a protective pathway multiple synergistic protective pathway
27 Environmental microbes with allergy protective effects identification of unique mechanisms Staphylococcus sciuri TLR2; NOD2 anti-inflammatory Hagner-Benes, 2013 DC-activation, (TH1/TH2/TH17) but no IL-12p35/70
28 Environmental microbes with allergy protective effects identification of unique mechanisms Staphylococcus sciuri TLR2; NOD2 anti-inflammatory Hagner-Benes, 2013 DC-activation, (TH1/TH2/TH17) but no IL-12p35/70 Acinetobacter lwoffii TLR4 (TLR7,9) anti-inflammatory Holst, JACI 2007 DC-activation, (TH2) Conrad, JEM 2009 IL-12, delta-4, Jagged-1 TH1/IFN-γ dependent
29 Environmental microbes with allergy protective effects identification of unique mechanisms Staphylococcus sciuri TLR2; NOD2 anti-inflammatory Hagner-Benes, 2013 DC-activation, (TH1/TH2/TH17) but no IL-12p35/70 Acinetobacter lwoffii TLR4 (TLR7,9) anti-inflammatory Holst, JACI 2007 DC-activation, (TH2) Conrad, JEM 2009 IL-12, delta-4, Jagged-1 TH1/IFN-γ dependent Lactobacillus lactis TLR2; NOD2 anti-inflammatory Holst, JACI 2007 DCs/Monoc. TNF-α (TH2) Debarry, JACI 2007 some IFN-γ
30 Environmental microbes with allergy protective effects identification of unique mechanisms Staphylococcus sciuri TLR2; NOD2 anti-inflammatory Hagner-Benes, 2013 DC-activation, (TH1/TH2/TH17) but no IL-12p35/70 Acinetobacter lwoffii TLR4 (TLR7,9) anti-inflammatory Holst, JACI 2007 DC-activation, (TH2) Conrad, JEM 2009 IL-12, delta-4, Jagged-1 TH1/IFN-γ dependent Lactobacillus lactis TLR2; NOD2 anti-inflammatory Holst, JACI 2007 DCs/Monoc. TNF-α (TH2) Debarry, JACI 2007 some IFN-γ Bacillus licheniformis Vogel, JACI 2008 anti-th2, but TH1 pathology
31 The Team Cooperating Partners Erika von Mutius, LMU München Susan Prescott, Perth, University of Western Australia Otto Holst, Holger Heine, Forschungs-Zentrum Borstel Richard S. Blumberg, Harvard Medical School, Boston, USA Institute of Laboratory Medicine Holger Garn Petra Pfefferle Stefanie Hagner-Benes Dörthe Kesper Christoph Hudemann Ayse Kilic Ulrich Purath Daniel Potaczek
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