Significance Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched for Lactobacillus johnsonii , which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.

Background Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma. Objective To examine environmental factors associated with recurrent wheezing in inner-city environments. Methods The Urban Environment and Childhood Asthma (URECA) study examined a birth cohort at high risk for asthma (n=560) in Baltimore, Boston, New York, and St. Louis. Environmental assessments included allergen exposure, and in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age three. Results Cumulative allergen exposure over the first three years was associated with allergic sensitization, and sensitization at age three was related to recurrent wheeze. In contrast, first year exposure to cockroach, mouse and cat allergens was negatively associated with recurrent wheeze (OR 0.60, 0.65, and 0.75, p≤0.01). Differences in house-dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze. Conclusions In inner-city environments, children with the highest exposure to specific allergens and bacteria during their first year were least likely to develop recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life may be beneficial, and suggest new preventive strategies for wheezing and allergic diseases.

The Cretaceous period is generally considered to have been a time of warm climate. Evidence for cooler episodes exists, particularly in the early Cretaceous period, but the timing and significance of these cool episodes are not well constrained. The seasonality of temperatures is important for constraining equator-to-pole temperature gradients and may indicate the presence of polar ice sheets; however, reconstructions of Cretaceous sea surface temperatures are predominantly based on the oxygen isotopic composition of planktonic foraminifera that do not provide information about such intra-annual variations. Here we present intra-shell variations in delta18O values of rudist bivalves (Hippuritoidea) from palaeolatitudes between 8 degrees and 31 degrees N, which record the evolution of the seasonality of Cretaceous sea surface temperatures in detail. We find high maximum temperatures (approximately 35 to 37 degrees C) and relatively low seasonal variability (< 12 degrees C) between 20 degrees and 30 degrees N during the warmer Cretaceous episodes. In contrast, during the cooler episodes our data show seasonal sea surface temperature variability of up to 18 degrees C near 25 degrees N, comparable to the range found today. Such a large seasonal variability is compatible with the existence of polar ice sheets.

Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood atopy and asthma development. Here we examined gut microbiota maturation over the first year of life in infants at high risk for asthma (HR), and whether it is modifiable by early-life Lactobacillus supplementation. We performed a longitudinal comparison of stool samples collected from HR infants randomized to daily oral Lactobacillus rhamnosus GG (HRLGG) or placebo (HRP) for 6 months, and healthy (HC) infants. Meconium microbiota of HRP participants is distinct, follows a delayed developmental trajectory, and is primarily glycolytic and depleted of a range of anti-inflammatory lipids at 6 months of age. These deficits are partly rescued in HRLGG infants, but this effect was lost at 12 months of age, 6 months after cessation of supplementation. Thus we show that early-life gut microbial development is distinct, but plastic, in HR infants. Our findings offer a novel strategy for early-life preventative interventions.

No abstract

SummaryPrfA, a transcription factor structurally related to Crp/ Fnr, activates Listeria monocytogenes virulence genes during intracellular infection. We report two new PrfA* mutations causing the constitutive overexpression of the PrfA regulon. Leu-140Phe lies in a a a a D adjacent to the DNA-binding motif in the C-terminal domain, like a previously characterized PrfA* mutation (Gly-145Ser). Ile-45Ser, in contrast, maps to the N-terminal b b b b -roll, a structure similar to that of the Crp cAMP binding site. The in vitro transcriptional properties of recombinant PrfA* I45S and PrfA* G145S were compared to those of PrfA WT at two differentially regulated PrfA-dependent promoters, P plcA and P actA . The two PrfA* mutations increased the affinity for the target DNA to a different extent, and the differences in DNA binding (PrfA* G145S > PrfA* I45S >>> PrfA WT ) correlated with proportional differences in transcriptional activity. The use of the PrfA* proteins revealed that P plcA had a greater affinity for, and was more sensitive to, PrfA than P actA . RNA polymerase (RNAP) initiated transcription independently of PrfA at P plcA , but not at P actA , consistent with bandshift experiments suggesting that P plcA has a greater affinity for RNAP than P actA . Thus, differences in affinity for both PrfA and RNAP appear to determine the different expression pattern of PrfA-regulated promoters. Modelling of the PrfA* mutations in the crystal structure of PrfA and comparison with structure-function analyses of Crp, in which similar mutations lead to constitutively active (cAMPindependent) Crp* proteins, suggested that PrfA shares with Crp an analogous mechanism of cofactormediated allosteric shift. Our data support a regulatory model in which changes in PrfA-dependent gene expression are primarily accounted for by changes in PrfA activity.

Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases.

The iap gene encodes the protein p60, which is common to all Listeria species. A previous comparison of the DNA sequences indicated conserved and species-specific gene portions. Based on these comparisons, a combination consisting of only five different primers that allows the specific detection and differentiation ofListeria species with a single multiplex PCR and subsequent gel analysis was selected. One primer was derived from the conserved 3′ end and is specific for all Listeria species; the other four primers are specific for Listeria monocytogenes,L. innocua, L. grayi, or the three grouped species L. ivanovii, L. seeligeri, and L. welshimeri, respectively. The PCR method, which also enables the simultaneous detection of L. monocytogenes and L. innocua, was evaluated against conventional biotyping with 200 food hygiene-relevant Listeria strains. The results indicated the superiority of this technique. Thus, this novel type of multiplex PCR may be useful for rapid Listeria species confirmation and for identification of Listeria species for strains isolated from different sources.