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Maternal and Birth Chracterestics Are Associated with Infant Gut Microbial Composition
AB154 Abstracts
502
SUNDAY
Relationship Between Domestic Mouse Allergen Exposure Assessed in Settled Dust and Mouse Specific IgE, IgG and IgG4 Antibodies in Asthmatic Children Alan Zhou1, Adnan Divjan1, Wanda Phipatanakul, MD, MS2, Nina Balac1, Jalean Dominguez1, Elizabeth C. Matsui, MD, MHS3, Matthew S. Perzanowski, PhD1; 1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 2 Division of Pediatric Allergy/Immunology, Boston Children’s Hospital, Harvard University School of Medicine, Boston, MA, 3Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, MD. RATIONALE: The relationship between domestic exposure to animal allergens has been inconsistent across studies, with some reporting an IgE response and others a ‘modified Th2’ response (characterized by increased IgG4). METHODS: Children with asthma were evaluated for enrollment in a mouse allergen intervention trial. Mouse specific IgE (n5379) and Mus m 1 specific IgG and IgG4 (n5268) were measured in serum. Mus m 1 was measured in bed (n5384), bedroom floor (n5337) and kitchen (n5183) settled dust. Data were logarithmically transformed before Pearson’s correlations and linear regressions were tested. RESULTS: All allergen measures correlated (P<0.001; bedroom floor vs. kitchen: r50.39; bed vs. kitchen: r50.41; bed vs. bedroom floor: r50.74). IgE correlated with allergen measured from bed (r50.13, P50.009) and bedroom floor (r50.22, P<0.001), but not kitchen (r50.072, P50.34). IgG and IgG4 correlated with allergen in dust (r50.18–0.34; bedroom samples highest). IgG and IgG4 were correlated with anti-mouse IgE (r50.77 and 0.54, P<0.001). The ratio of IgG4/IgG was not correlated with allergen measures, but was inversely correlated with IgE (r5 -0.44, P<0.001). In a model with both variables, bedroom allergen (b50.23, P50.003) and the IgG4/IgE ratio (b5 -6.2, P<0.001) were independently associated with anti-mouse IgE. CONCLUSIONS: Allergen measured in bedroom dust showed stronger correlations with IgE and IgG antibodies than did allergen measured from the kitchen. The inverse relationship between the ratio of mouse specific IgG4/IgG and IgE, independent of current mouse exposure, suggests that in addition to current allergen exposure other susceptibilities may be important in determining the IgE response to mouse.
503
Maternal and Birth Chracterestics Are Associated with Infant Gut Microbial Composition Christine Cole Johnson, PhD, MPH, FAAAAI1, Suzanne Havstad, MA1, Edward M. Zoratti, MD, FAAAAI2, Kei Fujimura, PhD3, Alexandra R. Sitarik, MS1, Haejin Kim, MD2, Andrea Cassidy-Bushrow, PhD1, Kevin Bobbitt, PhD1, Nicholas W. Lukacs, PhD4, Kimberley J. Woodcroft, PhD1, Homer A. Boushey, Jr, MD, FAAAAI5, Dennis R. Ownby, MD, FAAAAI6, Ganesa R. Wegienka, PhD1, Albert M. Levin, PhD1, Susan V. Lynch, PhD3; 1Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, 2 Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, MI, 3University of California San Francisco, San Francisco, CA, 4University of Michigan, Ann Arbor, MI, 5University of California, San Francisco, San Francisco, CA, 6Department of Pediatrics, Georgia Regents University, Augusta, GA. RATIONALE: Numerous maternal and birth characteristics have been associated with the incidence of allergy and asthma. We hypothesized such factors could influence the development of these disorders by their effect on the early gut microbiome of the newborn, and studied these associations in a population-based birth cohort (WHEALS) from Metropolitan Detroit. METHODS: Microbiomes of infant stools collected at 1 and 6 month visits (time periods 1-5 months versus 6-11 months) were characterized by MiSeq sequencing of the 16S rRNA gene. Maternal and birth variables collected by phone interview and at clinic and home visits were related univariately to stool microbial community composition (sMCC) indices
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
(richness, evenness and diversity), as well as measures of between-sample microbiome composition similarity. RESULTS: Among 298 children, the mother being married and the baby having a higher gestational age were statistically significantly associated with decreased sMCC diversity, evenness and richness at both 1 and 6 months. Cigarette smoke exposure during pregnancy and urban (versus suburban) residence were significantly associated with higher diversity, evenness and richness at both time points. Children born by caesareansection versus vaginally and children of Black race/ethnicity had distinct microbial composition at 1 and 6 months (p<0.01). CONCLUSIONS: Our results imply that maternal and birth parameters often shown to be associated with pediatric allergic disorders are related to features of the infant sMCC, suggesting that these attributes could be on a causal pathway preceding gut microbiome community characteristics contributing to the developing immune system and the subsequent evolution of allergic diseases.
504
The Infant Gut Microbiome Mediates the Association Between Breastfeeding and Allergic-like Response to Pets in Children Alexandra R. Sitarik, MS1, Suzanne Havstad, MA1, Albert M. Levin, PhD1, Kei Fujimura, PhD2, Ganesa R. Wegienka, PhD1, Edward M. Zoratti, MD, FAAAAI3, Dennis R. Ownby, M.D. FAAAAI4, Haejin Kim, MD3, Homer A. Boushey, Jr, MD, FAAAAI5, Susan V. Lynch, PhD2, Christine Cole Johnson, PhD MPH FAAAAI1; 1Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, 2University of California San Francisco, San Francisco, CA, 3Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, MI, 4 Department of Pediatrics, Georgia Regents University, Augusta, GA, 5 University of California, San Francisco, San Francisco, CA. RATIONALE: The mechanism linking breastfeeding to childhood allergic outcomes is not well understood. The infant gut microbiome may play an important role in this association, as breastfeeding influences microbiome composition and function, features of which directly impact immune response. METHODS: Data from 298 infants enrolled in the Wayne County Health Environment Allergy and Asthma Longitudinal Study (WHEALS) birth cohort were analyzed. Using infant stool samples collected over the first 6 months of life (N5130), gut microbiome was profiled by 16S rRNA sequencing. Allergic-like response to pets at age 4 was defined as parental report of any coughing, wheezing, tightness, shortness of breath, runny nose, sneezing, or itchy eyes around pets. Compositional differences in the microbiome were evaluated using permutational multivariate analysis of variance. Tests of differential operational taxonomic unit (OTU) abundance were performed using zero-inflated negative binomial regression with false discovery rate adjustment (significance threshold q-value<0.05). RESULTS: Babies currently breastfed at 1 month were at decreased risk of developing allergic-like response to pets (p-value50.028). Both breastfeeding and allergic-like response to pets were significantly related to compositional variation in gut microbiome (p-value<0.001, p-value50.023, respectively). Of the 109 OTUs significantly associated with both breastfeeding and allergic-like response to pets, 77 (71%) were negatively associated with breastfeeding but positively associated with allergic-like response to pets. This subset of risk-increasing bacteria suppressed by breastfeeding were predominantly members of the family Lachnospiraceae [51 (66%)]. CONCLUSIONS: Breastfeeding in infancy may protect against gut enrichment of specific Lachnospiraceae bacteria which are associated with allergic-like response to pets in early childhood.
502
SUNDAY
Relationship Between Domestic Mouse Allergen Exposure Assessed in Settled Dust and Mouse Specific IgE, IgG and IgG4 Antibodies in Asthmatic Children Alan Zhou1, Adnan Divjan1, Wanda Phipatanakul, MD, MS2, Nina Balac1, Jalean Dominguez1, Elizabeth C. Matsui, MD, MHS3, Matthew S. Perzanowski, PhD1; 1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, 2 Division of Pediatric Allergy/Immunology, Boston Children’s Hospital, Harvard University School of Medicine, Boston, MA, 3Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, MD. RATIONALE: The relationship between domestic exposure to animal allergens has been inconsistent across studies, with some reporting an IgE response and others a ‘modified Th2’ response (characterized by increased IgG4). METHODS: Children with asthma were evaluated for enrollment in a mouse allergen intervention trial. Mouse specific IgE (n5379) and Mus m 1 specific IgG and IgG4 (n5268) were measured in serum. Mus m 1 was measured in bed (n5384), bedroom floor (n5337) and kitchen (n5183) settled dust. Data were logarithmically transformed before Pearson’s correlations and linear regressions were tested. RESULTS: All allergen measures correlated (P<0.001; bedroom floor vs. kitchen: r50.39; bed vs. kitchen: r50.41; bed vs. bedroom floor: r50.74). IgE correlated with allergen measured from bed (r50.13, P50.009) and bedroom floor (r50.22, P<0.001), but not kitchen (r50.072, P50.34). IgG and IgG4 correlated with allergen in dust (r50.18–0.34; bedroom samples highest). IgG and IgG4 were correlated with anti-mouse IgE (r50.77 and 0.54, P<0.001). The ratio of IgG4/IgG was not correlated with allergen measures, but was inversely correlated with IgE (r5 -0.44, P<0.001). In a model with both variables, bedroom allergen (b50.23, P50.003) and the IgG4/IgE ratio (b5 -6.2, P<0.001) were independently associated with anti-mouse IgE. CONCLUSIONS: Allergen measured in bedroom dust showed stronger correlations with IgE and IgG antibodies than did allergen measured from the kitchen. The inverse relationship between the ratio of mouse specific IgG4/IgG and IgE, independent of current mouse exposure, suggests that in addition to current allergen exposure other susceptibilities may be important in determining the IgE response to mouse.
503
Maternal and Birth Chracterestics Are Associated with Infant Gut Microbial Composition Christine Cole Johnson, PhD, MPH, FAAAAI1, Suzanne Havstad, MA1, Edward M. Zoratti, MD, FAAAAI2, Kei Fujimura, PhD3, Alexandra R. Sitarik, MS1, Haejin Kim, MD2, Andrea Cassidy-Bushrow, PhD1, Kevin Bobbitt, PhD1, Nicholas W. Lukacs, PhD4, Kimberley J. Woodcroft, PhD1, Homer A. Boushey, Jr, MD, FAAAAI5, Dennis R. Ownby, MD, FAAAAI6, Ganesa R. Wegienka, PhD1, Albert M. Levin, PhD1, Susan V. Lynch, PhD3; 1Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, 2 Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, MI, 3University of California San Francisco, San Francisco, CA, 4University of Michigan, Ann Arbor, MI, 5University of California, San Francisco, San Francisco, CA, 6Department of Pediatrics, Georgia Regents University, Augusta, GA. RATIONALE: Numerous maternal and birth characteristics have been associated with the incidence of allergy and asthma. We hypothesized such factors could influence the development of these disorders by their effect on the early gut microbiome of the newborn, and studied these associations in a population-based birth cohort (WHEALS) from Metropolitan Detroit. METHODS: Microbiomes of infant stools collected at 1 and 6 month visits (time periods 1-5 months versus 6-11 months) were characterized by MiSeq sequencing of the 16S rRNA gene. Maternal and birth variables collected by phone interview and at clinic and home visits were related univariately to stool microbial community composition (sMCC) indices
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
(richness, evenness and diversity), as well as measures of between-sample microbiome composition similarity. RESULTS: Among 298 children, the mother being married and the baby having a higher gestational age were statistically significantly associated with decreased sMCC diversity, evenness and richness at both 1 and 6 months. Cigarette smoke exposure during pregnancy and urban (versus suburban) residence were significantly associated with higher diversity, evenness and richness at both time points. Children born by caesareansection versus vaginally and children of Black race/ethnicity had distinct microbial composition at 1 and 6 months (p<0.01). CONCLUSIONS: Our results imply that maternal and birth parameters often shown to be associated with pediatric allergic disorders are related to features of the infant sMCC, suggesting that these attributes could be on a causal pathway preceding gut microbiome community characteristics contributing to the developing immune system and the subsequent evolution of allergic diseases.
504
The Infant Gut Microbiome Mediates the Association Between Breastfeeding and Allergic-like Response to Pets in Children Alexandra R. Sitarik, MS1, Suzanne Havstad, MA1, Albert M. Levin, PhD1, Kei Fujimura, PhD2, Ganesa R. Wegienka, PhD1, Edward M. Zoratti, MD, FAAAAI3, Dennis R. Ownby, M.D. FAAAAI4, Haejin Kim, MD3, Homer A. Boushey, Jr, MD, FAAAAI5, Susan V. Lynch, PhD2, Christine Cole Johnson, PhD MPH FAAAAI1; 1Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, 2University of California San Francisco, San Francisco, CA, 3Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, MI, 4 Department of Pediatrics, Georgia Regents University, Augusta, GA, 5 University of California, San Francisco, San Francisco, CA. RATIONALE: The mechanism linking breastfeeding to childhood allergic outcomes is not well understood. The infant gut microbiome may play an important role in this association, as breastfeeding influences microbiome composition and function, features of which directly impact immune response. METHODS: Data from 298 infants enrolled in the Wayne County Health Environment Allergy and Asthma Longitudinal Study (WHEALS) birth cohort were analyzed. Using infant stool samples collected over the first 6 months of life (N5130), gut microbiome was profiled by 16S rRNA sequencing. Allergic-like response to pets at age 4 was defined as parental report of any coughing, wheezing, tightness, shortness of breath, runny nose, sneezing, or itchy eyes around pets. Compositional differences in the microbiome were evaluated using permutational multivariate analysis of variance. Tests of differential operational taxonomic unit (OTU) abundance were performed using zero-inflated negative binomial regression with false discovery rate adjustment (significance threshold q-value<0.05). RESULTS: Babies currently breastfed at 1 month were at decreased risk of developing allergic-like response to pets (p-value50.028). Both breastfeeding and allergic-like response to pets were significantly related to compositional variation in gut microbiome (p-value<0.001, p-value50.023, respectively). Of the 109 OTUs significantly associated with both breastfeeding and allergic-like response to pets, 77 (71%) were negatively associated with breastfeeding but positively associated with allergic-like response to pets. This subset of risk-increasing bacteria suppressed by breastfeeding were predominantly members of the family Lachnospiraceae [51 (66%)]. CONCLUSIONS: Breastfeeding in infancy may protect against gut enrichment of specific Lachnospiraceae bacteria which are associated with allergic-like response to pets in early childhood.