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Principal Investigator: Christine C Johnson
Organization: HENRY FORD HEALTH SYSTEM
Fiscal Year: 2024
Award: $2,818,591
Funding agency: National Institute of Allergy and Infectious Diseases
This application builds on the findings of our initial P01 designed to examine relationships between
environmental factors, especially pets, the infant gut microbiota and pediatric allergic asthma. We have shown
that: 1) dogs alter the microbial composition of dust in homes, 2) children born into homes with dogs have
different developmental patterns of gut microbiota and of IgE, 3) a distinct pattern of gut microbial composition
at 1 month of age is related to heightened risk of sensitization to multiple allergens at 2 years and of asthma at
4 years, and this pattern is influenced by numerous maternal characteristics, 4) sensitization to multiple food
and inhalant allergens at 2 years is strongly related to asthma at 10 years, 5) the metabolic profiles of stools
are related to later allergic sensitization 6) 12,13-DiHOME, a metabolite in stool, promotes development of Th2
lymphocytes and lowers development of Treg lymphocytes in an in vitro assay, and 7) in another study, the
meconial microbiota is distinct in neonates born to mothers with asthma. Our complementary mouse studies
have shown that: 1) gavaging with dust from homes with dogs reduces lung inflammation from allergen
sensitization and from respiratory syncytial virus (RSV) infection, 2) dog dust gavaged mice have increases in
Lactobacillus johnsonii in their ceca 3) oral administration of live L. johnsonii confers protection against
pulmonary inflammation induced by allergen and RSV, 4) L. johnsonii alters the function of bone marrow-
derived dendritic cells, 5) mice orally supplemented with L. johnsonii have altered serum metabolic profiles,
and 6) mouse pups born to L. johnsonii-supplemented mothers are protected against allergen challenge and
RSV infection. Collectively these findings showing the influence of maternal factors provide the basis for this
application's focus on the maternal gut and vaginal microbiotas during pregnancy, and how these relate to
infant gut microbial development and risk of allergic asthma. Project 1 focuses on the relationship of maternal
environmental and dietary factors, including maternal and infant gut microbiotas, to the child's developing a
high-risk for asthma phenotype by age 2 years. Project 2 proposes a detailed examination of relationships
between maternal and child microbiota, breast milk composition and IgE development amongst a cohort of
pregnancies in which the mother has current allergic asthma. Project 3 synergistically interacts with Projects 1
& 2 and also uses specimens from 10-year-old allergic asthma cases and controls in the initial P01 birth cohort
to examine gut microbes producing metabolites associated with a lowered risk of allergic inflammation and how
they are transferred from mother and established in offspring. Project 4 will use mouse models to examine the
relationships between manipulation of maternal microbiota and immune development in offspring. We
anticipate that together these studies will show that interventions directed at the gut microbiota of mothers
during pregnancy and of high-risk neonates after birth could reduce the risk of allergic asthma in childhood.
Such findings would provide the foundations of a rational strategy to prevent allergic asthma.
Terms: <0-11 years old><0-4 weeks old><10 year old><10 years of age><2 year old><2 years of age><21+ years old><Address><Adult><Adult Human><Affect><Age Months><Alimentary Canal><Allergens><Allergic><Allergic Disease><Allergic asthma><Allergic inflammation><Allergy><Asthma><Asthma in Children><Bacteria><Birth><Blood Serum><Bone Marrow><Bone Marrow Reticuloendothelial System><Breast Feeding><Breast Milk><Breast fed><Breastfed><Breastfeeding><Breastmilk><Bronchial Asthma><Canine Species><Canis familiaris><Characteristics><Child><Child Youth><Childhood><Childhood Asthma><Children (0-21)><Collection><Communities><Community Developments><Consensus><Dendritic Cells><Development><Dietary Factors><Digestive Tract><Dogs><Dogs Mammals><Dust><Environment><Environmental Exposure><Environmental Factor><Environmental Risk Factor><Exhibits><Exposure to><Extrinsic asthma><Feces><Female><Food><Foundations><GI Tract><GI microbiota><Gastrointestinal Tract><Gastrointestinal microbiota><Gastrointestinal tract structure><Gestation><Goals><Health><Home><House Dust><Human><Human Milk><Human Mother's Milk><Hypersensitivity><IgE><Immune><Immune system><Immunes><Immunoglobulin E><Incidence><Infant><Infant Development><Inflammation><Inhalant dose form><Intervention><Intervention Strategies><Joints><Lactobacillus><Life><Lung Inflammation><Lymphatic cell><Lymphocyte><Lymphocytic><Mammary Gland Milk><Maternal Exposure><Metabolic><Mice><Mice Mammals><Microbe><Modern Man><Mother's Milk><Mothers><Murine><Mus><Newborn Infant><Newborns><Oral Administration><Oral Drug Administration><Organism><Partner in relationship><Parturition><Pattern><Pediatric asthma><Phenotype><Pneumonitis><Population><Pregnancy><Pregnant Women><Prevalence><Prevention><Preventive><Primary Prevention><Pulmonary Inflammation><RSV infection><Regulatory T-Lymphocyte><Research><Research Specimen><Respiratory Syncytial Virus Infections><Respiratory syncytial virus><Risk><Risk Reduction><Serum><Shotguns><Skin><Source><Specimen><Systems Development><Time><Treg><United States><Vagina><Vaginal birth><Vaginal delivery><Vaginal delivery procedure><Veiled Cells><Virus><Work><adulthood><age 10 years><age 2 years><aged 2 years><aged two years><alimentary tract><atopic asthma><canine><cohort><community microbes><design><designing><developmental><digestive canal><domestic dog><enteric microbial community><enteric microbiota><environmental risk><expectant mother><expecting mother><extrinsic allergic asthma><feeding><gastrointestinal><gastrointestinal microbial flora><gene function><gut commensal><gut community><gut flora><gut microbe community><gut microbes><gut microbial community><gut microbial composition><gut microbial consortia><gut microbial species><gut microbiota><gut microbiotic><gut microflora><high risk><home dust><homes><household dust><in utero><in vitro Assay><individualized prevention><inhalant><interventional strategy><intestinal flora><intestinal microbes><intestinal microbiota><intestinal microflora><intestinal tract microflora><intraoral drug delivery><kids><life-style factor><lifestyle factors><living system><lymph cell><mate><maternal flora><maternal microbiota><maternal milk><metabolic profile><metagenome sequencing><metagenomic sequencing><microbial><microbial community><microbial composition><microbial consortia><microbial flora><microbiota><microbiota composition><microbiota derived metabolites><microbiota metabolites><microflora><mouse model><multispecies consortia><murine model><neonate><newborn child><newborn children><offspring><oral supplement><oral supplementation><pediatric><personalized prevention><pet animal><pets><polymicrobial community><precision prevention><pregnant mothers><prenatal><prevent><preventing><protective effect><pup><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><regulatory T-cells><residential dust><risk-reducing><shot gun><stool><suckling><ten year old><ten years of age><two year old><two years of age><unborn><vagina microbiota><vaginal flora><vaginal microbial community><vaginal microbiota><vaginal microflora><youngster>