Household Dust Exposure Modifies Gut Microbiome Composition and Airway Health Susan V. Lynch , PhD Associate Professor of Medicine Director Colitis and Crohn’s Disease Research Core Division of Gastroenterology, Department of Medicine, University of California San Francisco. Pediatric Asthma Childhood Allergic Disease and Asthma •  Factors associated with childhood allergic disease development: - Early life antibiotic exposure - Formula feeding - Caesarian section delivery - Lack of maternal exposure to animals during pregnancy - Maternal antibiotic use - Lack of early life furred pet exposure Fujimura et al, ERAI 2010 •  Early-life gastrointestinal microbial outgrowth is associated with childhood allergic disease development Early Life Microbiome Development Rauch et al, unpublished data Is the Indoor Microbial Environment Related to Allergic Disease? 86.9% (68.7% in residence) 7.6% 5.5% Klepeis et al. 2001 J Expo Anal Env Epid 11:231-52 Is House Dust Microbiome Related to Childhood Allergic Outcomes? Dust & Data available N=104 Neither n=29 Wheeze Only n=26 Atopy Only n=25 Atopy defined as: IgE ≥ 0.35 for any aeroallergen was considered positive IgE < 0.10 for all aeroallergens was considered negative Wheeze defined as: > 2 episodes of wheeze, with at least 1 occurring at age 3 Atopy & Wheeze n=24 Dust Microbiome Composition is Related to Clinical Outcomes ~ 70 taxa in household dust that are associated with protection against disease development – human gut inhabitants Does pet ownership influence the microbial exposures in households? Majority of bacteria significantly enriched in Dogowning houses haveCbeen described D NP in the human gut microbiome Fujimura KE et al. J Allergy Clin Immunol. 2010 126(2): 410-2 Can Environmental Microbial Exposure Influence Airway Responses? Dog VS No pets Berlin, A.A., et al, Lab Invest. 2006 Jun;86(6):557-65. House Dust Exposure Changes Airway Response to Allergen Fujimura at al, PNAS, 2013 Gut Microbiome is Distinct in Protected Mice Lactobacillus johnsonii Fujimura at al, PNAS, 2013 Lactobacillus Isolation & Supplementation Daily gavage Lactobacillus sp. 1 x 107 Lactobacillus gavage 2 X per week Fujimura at al, PNAS, 2013 Lactobacillus Supplementation Protects against Airway Allergen Challenge Fujimura at al, PNAS, 2013 L. johnsonii Supplementation Protects Against Viral Infection B A Change in Resistance (cm H2 0/ml/sec) 6 RSV+PBS RSV+Live L.J RSV+HK L.J 4 * 2 V S R R S V -l -H iv .K e .L L. .j. j. R S V -P B S 0 C D 15000 12500 8 10000 600 * RSV + H.K. L. johnsonii 2 + C 8+ D C 4+ C D 69 + D C c/ 11 D C c/ IFNg 11 IL-17 D IL-13 69 D b 11 C D * IL-5 * 0 0 IL-4 * * D * 200 * * 4 C 400 Uninfected RSV RSV + L. johnsonii C pg/ml 2500 6 8 5000 Cell Number X 105 RSV RSV + L. johnsonii RSV + H.K. L. johnsonii 7500 Fujimura at al, PNAS, 2013 L. johnsonii Reshapes the Murine Cecal Microbiome •  No enrichment of Lachnospiraceae, Peptococcaceae or Bacillaceae •  Environmentally-sourced species required for full protection Fujimura at al, PNAS, 2013 Conclusions •  Local environmental exposures are related to clinical outcomes of childhood allergic disease •  Gut microbiome can be influenced by environmental exposures •  Gut microbiome manipulation leads to altered host immune response at remote mucosal surfaces What’s next? Acknowledgements UCSF Kei Fujimura Marcus Rauch Michelle McKean Homer Boushey Michael Cabana Henry Ford Hospital Chris Johnson Suzanne Havstad Ed Zoratti Kim Woodcroft Kevin Bobbitt Ganessa Wegienka University of Michigan Nick Lukacs Tine Demoor URECA study Jim Gern Bob Wood Homer Boushey Augustin Calatroni Henry Lynn Bill Busse Georgia Health Sciences Health System Dennis Ownby Lawrence Berkeley National Lab Eoin Brodie Second Genome Jannet Warrington Todd DeSantis Funding NIH/NIAID NIH/NIAID NIH/NCCAM UCSF Program for Breakthrough Biomedical Research Broad Foundation Sloan Foundation Cystic Fibrosis Foundation Janssen Pharmaceuticals Inc. Pfizer Inc.