The Legacy of Redlining: Increasing Childhood Asthma Disparities Through Neighborhood Poverty.

RATIONALE: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. OBJECTIVES: To determine if the 1930's racist policy of redlining led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). METHODS: We categorized census tracts at birth of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into A, B, C, or D categories as defined by the Home Owners Loan Corporation (HOLC), with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract including the percentage of low-income households, the CDC's social vulnerability index (SVI), and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through census tract-level mediators adjusting for individual-level covariates. MEASUREMENTS AND MAIN RESULTS: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6% and 13.2% resided in census tracts with a HOLC grade of D. In mediation analyses, residing in grade D tracts (aOR = 1.03 [95%CI 1.01,1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for SVI and other tract-level variables. CONCLUSIONS: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.

Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

The impact of prenatal dog keeping on infant gut microbiota development.

INTRODUCTION: Prenatal and early-life dog exposure has been linked to reduced childhood allergy and asthma. A potential mechanism includes altered early immune development in response to changes in the gut microbiome among dog-exposed infants. We thus sought to determine whether infants born into homes with indoor dog(s) exhibit altered gut microbiome development. METHODS: Pregnant women living in homes with dogs or in pet-free homes were recruited in southeast Michigan. Infant stool samples were collected at intervals between 1 week and 18 months after birth and microbiome was assessed using 16S ribosomal sequencing. Perinatal maternal vaginal/rectal swabs and stool samples were sequenced from a limited number of mothers. Mixed effect adjusted models were used to assess stool microbial community trajectories comparing infants from dog-keeping versus pet-free homes with adjustment for relevant covariates. RESULTS: Infant gut microbial composition among vaginally born babies became less similar to the maternal vaginal/rectal microbiota and more similar to the maternal gut microbiota with age-related accumulation of bacterial species with advancing age. Stool samples from dog-exposed infants were microbially more diverse (p = .041) through age 18 months with enhanced diversity most apparent between 3 and 6 months of age. Statistically significant effects of dog exposure on ß-diversity metrics were restricted to formula-fed children. Across the sample collection period, dog exposure was associated with Fusobacterium genera enrichment, as well as enrichment of Collinsella, Ruminococcus, Clostridaceae and Lachnospiraceae OTUs. CONCLUSION: Prenatal/early-life dog exposure is associated with an altered gut microbiome during infancy and supports a potential mechanism explaining lessened atopy and asthma risk. Further research directly linking specific dog-attributable changes in the infant gut microbiome to the risk of allergic disorders is needed.

Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents.

BACKGROUND: Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS. METHODS: Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10. RESULTS: A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R2 = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development. CONCLUSIONS: Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed. IMPACT: Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs. We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years. We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years. This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development.

Infant gut bacterial community composition and food-related manifestation of atopy in early childhood.

BACKGROUND: Immunoglobulin E-mediated food allergy (IgE-FA) has emerged as a global public health concern. Immune dysregulation is an underlying mechanism for IgE-FA, caused by "dysbiosis" of the early intestinal microbiota. We investigated the association between infant gut bacterial composition and food-related atopy at age 3-5 years using a well-characterized birth cohort. METHODS: The study definition of IgE-FA to egg, milk, or peanut was based on physician panel retrospective review of clinical and questionnaire data collected from birth through age 3-5 years. Using 16S rRNA sequencing, we profiled the bacterial gut microbiota present in stool specimens collected at 1 and 6 months of age. RESULTS: Of 447 infants with data for analysis, 44 (9.8%) met physician panel review criteria for IgE-FA to ≥1 of the three allergens. Among children classified as IgE-FA at 3-5 years, infant stool samples showed significantly less diversity of the gut microbiota compared with the samples of children classified as no IgE-FA at age 3-5 years, especially for milk and peanut (all covariate-adjusted p's for alpha metrics <.007). Testing of individual operational taxonomic units (OTUs) revealed 6-month deficiencies in 31 OTUs for IgE-FA compared with no IgE-FA, mostly in the orders Lactobacillales, Bacteroidales, and Clostridiales. CONCLUSIONS: Variations in gut microbial composition in infant stool were associated with a study definition of IgE-FA at 3-5 years of age. This included evidence of a lack of bacterial diversity, deficiencies in specific OTUs, and delayed microbial maturation. Results support dysbiosis in IgE-FA pathogenesis.

Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood.

Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored.Objectives: To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry.Methods: Data from seven U.S. birth cohorts (n = 3,786) from the CREW (Children's Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) (n = 1,308) and, for the first time, in African American (AA) (n = 620) children.Measurements and Main Results: The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children.Conclusions: These results indicate that 17q12-21 is a "wheezing locus," and this association may reflect an early life susceptibility to respiratory viruses common to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.

Pediatric asthma incidence rates in the United States from 1980 to 2017.

BACKGROUND: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective. OBJECTIVE: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history. METHODS: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated. RESULTS: The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females. CONCLUSIONS: US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.

Increased risk of asthma at age 10 years for children sensitized to multiple allergens.

BACKGROUND: Childhood sensitization patterns have been previously found to be related to variable risk of early life allergic disease in several birth cohorts. OBJECTIVE: To determine whether these risks persist into later childhood. METHODS: In the birth cohort of the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, previous latent class analysis based on sensitization to 10 allergens found the following 4 early life sensitization patterns at age 2 years: "highly sensitized," "milk/egg dominated," "peanut and inhalant(s)," and "low to no sensitization." At an age 10 study-specific visit, children were evaluated by an allergist for current asthma and atopic dermatitis through a physical examination and interviews with the child and parent or guardian. Total and specific immunoglobulin E (IgE), spirometry, and methacholine challenge were also completed. RESULTS: Compared with children sensitized to none or 1 allergen, children sensitized to 4 or more food and inhalant allergens at age 2 had the highest risk of current asthma (relative risk [RR], 4.42; 95% confidence interval [CI], 2.58-7.59; P < .001) and bronchial hyperresponsiveness (RR, 1.77; 95% CI, 1.29-2.42; P < .001). In addition, they had the highest levels of total IgE (geometric mean, 800 IU/mL; 95% CI, 416-1536) among the 4 groups. Risk of current atopic dermatitis did not depend on pattern of sensitization but remained increased for children with any sensitization (RR, 2.23; 95% CI, 1.40-3.55; P < .001). No differences in spirometry (forced expiratory volume in 1 second, forced expiratory flow between 25% and 75%, and forced expiratory volume in 1 second/forced vital capacity) were identified. CONCLUSION: The previously reported importance of a specific pattern of sensitization in early life (sensitization to ≥4 inhalant and food allergens) continues to be associated with an increased risk of asthma, bronchial hyperresponsiveness, and high total IgE at age 10 years.

Participant-level characteristics differ by recruitment setting when evaluating a behavioral intervention targeting adolescents with asthma.

OBJECTIVE: The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors. METHODS: The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control). RESULTS: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001). CONCLUSION: Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.

Association between cesarean delivery types and obesity in preadolescence.

BACKGROUND/OBJECTIVES: The association between mode of delivery and childhood obesity remains inconclusive. Because few studies have separated C-section types (planned or unplanned C-section), our objective was to assess how these subtypes relate to preadolescent obesity. SUBJECTS/METHODS: The study consisted of 570 maternal-child pairs drawn from the WHEALS birth cohort based in Detroit, Michigan. Children were followed-up at 10 years of age where a variety of anthropometric measurements were collected. Obesity was defined based on BMI percentile (≥95th percentile), as well as through Gaussian finite mixture modeling on the anthropometric measurements. Risk ratios (RRs) and 95% confidence intervals (CIs) for obesity comparing planned and unplanned C-sections to vaginal deliveries were computed, which utilized inverse probability weights to account for loss to follow-up and multiple imputation for covariate missingness. Mediation models were fit to examine the mediation role of breastfeeding. RESULTS: After adjusting for marital status, maternal race, prenatal tobacco smoke exposure, maternal age, maternal BMI, any hypertensive disorders during pregnancy, gestational diabetes, prenatal antibiotic use, child sex, parity, and birthweight z-score, children born via planned C-section had 1.77 times higher risk of obesity (≥95th percentile), relative to those delivered vaginally ((95% CI) = (1.16, 2.72); p = 0.009). No association was found comparing unplanned C-section to vaginal delivery (RR (95% CI) = 0.75 (0.45, 1.23); p = 0.25). The results were similar but slightly stronger when obesity was defined by anthropometric class (RR (95% CI) = 2.78 (1.47, 5.26); p = 0.002). Breastfeeding did not mediate the association between mode of delivery and obesity. CONCLUSIONS: These findings indicate that children delivered via planned C-section-but not unplanned C-section-have a higher risk of preadolescent obesity, suggesting that partial labor or membrane rupture (typically experienced during unplanned C-section delivery) may offer protection. Additional research is needed to understand the biological mechanisms behind this effect, including whether microbiological differences fully or partially account for the association.

Racial disparities in allergic outcomes persist to age 10 years in black and white children.

BACKGROUND: Previous analyses in the WHEALS birth cohort demonstrated that black children are more likely to experience allergic outcomes than white children by age 2 years. The results could not be explained by a host of variables. OBJECTIVE: Assess whether racial disparities persisted to age 10 years and determine whether any differences could be explained by a panel of variables related to early life exposures in WHEALS. METHODS: At age 10 years, WHEALS children (n = 481) completed skin prick testing, spirometry and methacholine challenge, and a physician examination for eczema and asthma. Allergen-specific immunoglobulin Es (sIgE) and total IgE were measured. Inverse probability weighting with logistic and linear regression models was used to assess associations between race (black or white) and the outcomes. RESULTS: Black children fared worse than white children with respect to each outcome. Black children were more likely to have eczema, asthma, sensitization (≥1 sIgE ≥ 0.35 IU/L) and at least 1 positive skin pick test; however, some variability was present in the magnitudes of association within subgroups defined by delivery mode, sex of the child, prenatal indoor dog exposure, and firstborn status. In some subgroups, black children were also more likely to have higher total IgE and worse pulmonary function test measures (PC 20 ≤ 25 mg/mL, % predicted forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1]/FVC, forced expiratory flow from 25% to 75% of vital capacity [FEF25-75]). Confounding did not explain these differences. CONCLUSION: Racial differences persisted in this cohort through age 10 years. Future studies should include potentially important, but rarely studied factors such as segregation and structural racism, because these factors could explain the observed racial differences.

The Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium: design, methods, and study population.

BACKGROUND: Single birth cohort studies have been the basis for many discoveries about early life risk factors for childhood asthma but are limited in scope by sample size and characteristics of the local environment and population. The Children's Respiratory and Environmental Workgroup (CREW) was established to integrate multiple established asthma birth cohorts and to investigate asthma phenotypes and associated causal pathways (endotypes), focusing on how they are influenced by interactions between genetics, lifestyle, and environmental exposures during the prenatal period and early childhood. METHODS AND RESULTS: CREW is funded by the NIH Environmental influences on Child Health Outcomes (ECHO) program, and consists of 12 individual cohorts and three additional scientific centers. The CREW study population is diverse in terms of race, ethnicity, geographical distribution, and year of recruitment. We hypothesize that there are phenotypes in childhood asthma that differ based on clinical characteristics and underlying molecular mechanisms. Furthermore, we propose that asthma endotypes and their defining biomarkers can be identified based on personal and early life environmental risk factors. CREW has three phases: 1) to pool and harmonize existing data from each cohort, 2) to collect new data using standardized procedures, and 3) to enroll new families during the prenatal period to supplement and enrich extant data and enable unified systems approaches for identifying asthma phenotypes and endotypes. CONCLUSIONS: The overall goal of CREW program is to develop a better understanding of how early life environmental exposures and host factors interact to promote the development of specific asthma endotypes.

The impact of traditional literacy and education on health literacy in adolescents with asthma.

Introduction: People with low health literacy have poorer self-management of chronic diseases like asthma. Studies of parent health literacy and education level on the management of children's chronic illnesses reveal inconclusive results. We hypothesized a correlation between parent and adolescent health literacy in teens with asthma. Methods: Sociodemographic data were obtained; health literacy was assessed on adolescents and parents with three instruments: Rapid Estimate of Adolescent/Adult Literacy in Medicine (REALM), Single Item Literacy Screener (SILS) and Newest Vital Sign (NVS). Agreement between scores was examined by calculating weighted kappa statistics and performing Bowkers test of symmetry. Results: In all, 243 adolescents and 203 parents completed health literacy assessments yielding 198 paired observations. 9th-12th graders, 60.6% female, 72.7% African-American (AA), mean age: 15.3 years (±0.9). Parent education ranged from < high school (19.1%) to college graduate (24.0%). Agreement between adolescent and parent scores was poor: REALM (κw = 0.26), SILS (κw = 0.12), and NVS (κw = 0.29) and disagreement did not significantly differ by race. Positive correlations of moderate strength (overall and between racial groups) were found between reading scores and both REALM and NVS scores, and between REALM and NVS scores. Due to the inverse relationship of SILS scores with health literacy level, SILS scores (overall and between racial groups) were weakly and negatively correlated with reading scores, REALM and NVS. Conclusion: Correlation between education level and traditional literacy suggests that these are contributing factors to the health literacy of adolescents with asthma. Correlation between adolescent and caregiver health literacy was not supported.

NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and childhood asthma-implications for home environmental intervention in asthma prevention and management.

Environmental exposures have been recognized as critical in the initiation and exacerbation of asthma, one of the most common chronic childhood diseases. The National Institute of Allergy and Infectious Diseases; National Institute of Environmental Health Sciences; National Heart, Lung, and Blood Institute; and Merck Childhood Asthma Network sponsored a joint workshop to discuss the current state of science with respect to the indoor environment and its effects on the development and morbidity of childhood asthma. The workshop included US and international experts with backgrounds in allergy/allergens, immunology, asthma, environmental health, environmental exposures and pollutants, epidemiology, public health, and bioinformatics. Workshop participants provided new insights into the biologic properties of indoor exposures, indoor exposure assessment, and exposure reduction techniques. This informed a primary focus of the workshop: to critically review trials and research relevant to the prevention or control of asthma through environmental intervention. The participants identified important limitations and gaps in scientific methodologies and knowledge and proposed and prioritized areas for future research. The group reviewed socioeconomic and structural challenges to changing environmental exposure and offered recommendations for creative study design to overcome these challenges in trials to improve asthma management. The recommendations of this workshop can serve as guidance for future research in the study of the indoor environment and on environmental interventions as they pertain to the prevention and management of asthma and airway allergies.

Rural Asthma: Current Understanding of Prevalence, Patterns, and Interventions for Children and Adolescents.

PURPOSE OF REVIEW: Asthma is the most common chronic illness of children and adolescents in the USA. While asthma has been understood to disproportionately affect urban dwellers, recent investigations have revealed rural pediatric asthma prevalence to be very similar to urban and to be more closely correlated with socioeconomic and environmental factors than geographic location or population density. RECENT FINDINGS: Rural children experience factors unique to location that impact asthma development and outcomes, including housing quality, cigarette smoke exposure, and small/large-scale farming. Additionally, there are challenging barriers to appropriate asthma care that frequently are more severe for those living in rural areas, including insurance status, lack of primary care providers and pulmonary specialists, knowledge deficits (both patient and provider), and a lack of culturally tailored asthma interventions. Interventions designed to address rural pediatric asthma disparities are more likely to be successful when targeted to specific challenges, such as the use of school-based services or telemedicine to mitigate asthma care access issues. Continued research on understanding the complex interaction of specific rural environmental factors with host factors can inform future interventions designed to mitigate asthma disparities.

Breast Milk Transforming Growth Factor ß Is Associated With Neonatal Gut Microbial Composition.

BACKGROUND AND OBJECTIVES: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. METHODS: A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection.

Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.