Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.

Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years.

Human interferon-inducible protein 10 (IP-10) differs from most chemokines in its apparent specificity for activated T lymphocytes. We hypothesized that IP-10 was relevant not only for recruiting T cells to inflammatory sites, but also for regulating cytokine synthesis patterns. We examined the effect of recombinant human IP-10 (rhIP-10) on human interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by fresh peripheral blood mononuclear cells. We demonstrate for the first time that this CXC chemokine selectively up-regulates human T cell cytokine synthesis, with enhancement selectively targeted to promotion of Th1-like dominance. Superantigen (TSST-1), soluble anti-CD3 mAb, and phytohemagglutinin were used to activate distinct intracellular signaling pathways, thereby inducing quantitatively different IFN-gamma:IL-4 ratios. Selective enhancement of IFN-gamma responses was consistently observed, with median increases of 105-470%. Environmental antigens (Ag) were used to evaluate IP-10's effect on CD4-dependent, chloroquine-sensitive cytokine synthesis. Ag-driven IFN-gamma responses exhibited median 19- to 30-fold increases in the presence of nanomolar concentrations of rhIP-10. IL-4 responses were neither enhanced nor inhibited under any of the conditions tested. These findings suggest a potential role for this T cell-focused chemokine in maintenance of the default Th1-like responses usually seen to environmental Ag and indicate a potential application in the modulation of Ag-driven responses in vivo.

Our gut microbiota provide a number of important functions, one of which is the metabolism of dietary fiber and other macronutrients that are undigested by the host. The main products of this fermentation process are short-chain fatty acids (SCFAs) and other intermediate metabolites including lactate and succinate. Production of these metabolites is dependent on diet and gut microbiota composition. There is increasing evidence for the role of SCFAs in host physiology and metabolic processes as well as chronic inflammatory conditions such as allergic disease and obesity. We aimed to investigate differences in fecal SCFAs and intermediate metabolites in 163 infants at 3–5 months of age according to breastfeeding status. Compared to no exposure to human milk at time of fecal sample collection, exclusive breastfeeding was associated with lower absolute concentrations of total SCFAs, acetate, butyrate, propionate, valerate, isobutyrate, and isovalerate, yet higher concentrations of lactate. Further, the relative proportion of acetate was higher with exclusive breastfeeding. Compared to non-breastfed infants, those exclusively breastfed were four times more likely (aOR 4.50, 95% CI 1.58–12.82) to have a higher proportion of acetate relative to other SCFAs in their gut. This association was independent of birth mode, intrapartum antibiotics, infant sex, age, recruitment site, and maternal BMI or socioeconomic status. Our study confirms that breastfeeding strongly influences the composition of fecal microbial metabolites in infancy.