Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4 distinct milk groups. Little is known regarding whether maternal physiological status contributes to HMO variability. We characterized the trajectories of 20 major HMOs and explored whether maternal pre-pregnancy body mass index (ppBMI), mode of delivery, or parity may affect milk HMO composition. Using longitudinal breastmilk samples from healthy mothers (n = 290) across 7 European countries, we characterized HMO composion and employed mixed linear models to explore associations of maternal characteristics with individual HMOs. We observed HMO-specific temporal trajectories and milk group dependencies. We observed relatively small but significant differences in HMO concentrations based on maternal ppBMI, mode of delivery and parity. Our findings suggest that HMO composition to be regulated time-dependently by an enzyme as well as substrate availability and that ppBMI, mode of delivery, and parity may influence maternal physiology to affect glycosylation marginally within the initital period of lactation. Our observational study is the largest European standardized and longitudinal (up to 4 months) milk collection study assessing HMO concentrations and basic maternal characteristics. Time of lactation and milk groups had the biggest impact on HMO variation. Future studies need to elucidate these observations and assess the physiological significance for the breastfed infant.

Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE benefit hay fever1 and allergic asthma1,2. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation3-6. We therefore surveyed epigenetic association between serum IgE concentrations and methylation at loci concentrated in CpG islands (CGI) genome-wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes (PBL). We validated positive results in additional families and in subjects from the general population. We show here replicated associations with a meta-analysis false discovery rate <10−4 between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors, and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining 10 fold higher variance than that derived from large SNP GWAS3,4. The study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.

Potassium supplementation is associated with reduction of blood pressure in patients who are not on antihypertensive medication, and the effect is significant in hypertensive patients. The reduction in blood pressure significantly correlates with decreased daily urinary sodium-to-potassium ratio and increased urinary potassium. Patients with elevated blood pressure may benefit from increased potassium intake along with controlled or decreased sodium intake.

Human milk oligosaccharides (HMOs) are a major component of human milk, and play an important role in protecting the infant from infections. Preterm infants are particularly vulnerable, but have improved outcomes if fed with human milk. This study aimed to determine if the HMO composition of preterm milk differed from that of term milk at equivalent stage of lactation and equivalent postmenstrual age. In all, 22 HMOs were analyzed in 500 samples of milk from 25 mothers breastfeeding very preterm infants (< 32 weeks of gestational age, < 1500 g of birthweight) and 28 mothers breastfeeding term infants. The concentrations of most HMOs were comparable at equivalent postpartum age. However, HMOs containing α-1,2-linked fucose were reduced in concentration in preterm milk during the first month of lactation. The concentrations of a number of sialylated oligosaccharides were also different in preterm milk, in particular 3′-sialyllactose concentrations were elevated. At equivalent postmenstrual age, the concentrations of a number of HMOs were significantly different in preterm compared to term milk. The largest differences manifest around 40 weeks of postmenstrual age, when the milk of term infants contains the highest concentrations of HMOs. The observed differences warrant further investigation in view of their potential clinical impact.

Asthma is a chronic condition with unknown pathogenesis, and recent evidence suggests that enhanced airway epithelial chloride (Cl -) secretion plays a role in the disease. However, the molecular mechanism underlying Cl -secretion and its relevance in asthma pathophysiology remain unknown. To determine the role of the solute carrier family 26, member 9 (SLC26A9) Cl -channel in asthma, we induced Th2-mediated inflammation via IL-13 treatment in wild-type and Slc26a9-deficient mice and compared the effects on airway ion transport, morphology, and mucus content. We found that IL-13 treatment increased Cl -secretion in the airways of wildtype but not Slc26a9-deficient mice. While IL-13-induced mucus overproduction was similar in both strains, treated Slc26a9-deficient mice exhibited airway mucus obstruction, which did not occur in wild-type controls. In a study involving healthy children and asthmatics, a polymorphism in the 3′ UTR of SLC26A9 that reduced protein expression in vitro was associated with asthma. Our data demonstrate that the SLC26A9 Cl -channel is activated in airway inflammation and suggest that SLC26A9-mediated Cl -secretion is essential for preventing airway obstruction in allergic airway disease. These results indicate that SLC26A9 may serve as a therapeutic target for airway diseases associated with mucus plugging.