TitleMaternal and infant serum carotenoids are associated with infantile atopic dermatitis developmentTo the Editor,Various epidemiological studies have shown that eczema/atopic dermatitis (AD) in infancy is a risk for skin sensitization1 and development of allergic diseases later in life2.Carotenoids are natural pigments biosynthesized by bacteria, fungi, and plants, but not by mammals3; thus, they need to be supplied via dietary intake of vegetables and fruits or certain animal products. Carotenoids positively impact human health and prevents allergic reactions via their provitamin A activity and high antioxidant potential. However, previous studies using food frequency questionnaires that evaluated the association between maternal vegetable intake during pregnancy and eczema in offspring have shown inconsistent results4–6. As these studies did not measure the levels of individual carotenoids in the serum of mothers or children and in breast milk, appropriate nutritional interventions in maternal and early infant intake of vegetables for the prevention of AD remain unclear.In this study, we have measured the levels of total carotenoids and some of their sub-types in the serum of mothers and children and in maternal breast milk, to evaluate the association between carotenoid levels and the presence of AD at 1 year of age in infants.We compared participants’ characteristics and exposures by 1 year of age (Table S1); carotenoid, retinol, and α-tocopherol levels (Table 1) in the serum of participants, with and without AD at 1 year of age, were compared to those in the serum and breast milk of their respective mothers. We found that both the presence of eczema (OR, 31.7; 95%CI[13.2–76.0]) and S. aureus carriage in the skin by 6 months of age (OR, 5.20; 95%CI[2.30–11.75]) were associated with higher odds of AD development at 1 year of age. On the contrary, certain carotenoid levels in the serum and breast milk, including total carotenoids in the maternal blood, were associated with lower odds of AD at 1 year.To avoid multicollinearity in the regression analysis, we selected seven relevant predictive variables among the carotenoid data using VIP scores in the PLS analysis (Table S2). Stepwise logistic regression analysis using explanatory baseline characteristics, exposure by 1 year of age, and the seven selected carotenoid levels revealed that the following variables were significantly related to AD at 1 year of age (Table 2): presence of eczema by 6 months of age (OR, 34.5; P < 0.0001), maternal blood lutein level (unit OR, 0.002; P = 0.002), and infant blood lycopene level at 1 year (unit OR, 0.01; P = 0.007).One strength of this study is that multiple biological sample types were used as proxies for carotenoid intake. The lutein concentration in the maternal blood at 36 weeks of gestation, which was associated with a reduced AD risk at 1 year of age in the multivariate analysis, was significantly correlated with the cord blood lutein level (Table S3). This suggests that lutein ingested during pregnancy is transferred to the fetus and may have an inhibitory effect on the development of AD in infancy. Another strength of this study is that multiple carotenoids were evaluated simultaneously; the concentrations of lutein, zeaxanthin, α-carotene, β-carotene, and lycopene were strongly correlated, suggesting that these nutrients are absorbed together (Table S4).In conclusion, the results of this study suggest that children of mothers with low carotenoid intake during pregnancy are at higher risk for developing infantile AD and are ideal targets for early intervention in allergy prevention. Further studies are needed to clarify whether carotenoid supplementation during pregnancy/in lactating mothers and infants after weaning has a preventive effect on AD development in infancy.Table 1 Levels of each carotenoid, total carotenoids, retinol, and α-tocopherol in each type of sample in participants with or without atopic dermatitis at 1 year of age

BACKGROUND: Chemokine (C-C motif) ligand 17 (CCL17; also known as thymus and activation-regulated chemokine or TARC) is a pro-allergic factor, and high CCL17 levels in cord blood (CB) precede the allergic predisposition later in life. Offspring of pregnant mice treated with short-chain fatty acid (SCFA) have been shown to be protected against allergic diseases. The maternal microbial metabolome during pregnancy may affect foetal allergic immune responses. To examine this, the associations between CB CCL17 and gut SCFA levels in pregnant Japanese women were investigated here. METHODS: This study was conducted as part of the Chiba Study of Mother and Child Health; 434 healthy pregnant women were recruited. The CB CCL17 and maternal non-specific IgE levels were measured using CB sera at birth and maternal sera at 32 weeks of gestation. Stool samples were collected from pregnant women at 12 (n = 59) and 32 (n = 58) weeks of gestation and used for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. RESULTS: The CB CCL17 levels correlated negatively with butyrate concentrations at 12 weeks of gestation. In contrast, CB CCL17 levels correlated positively with isobutyrate levels at 12 weeks of gestation, and valerate and lactate concentrations at 32 weeks of gestation in maternal faeces. CONCLUSION: The metabolites in maternal faeces may alter the foetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring, even before birth.