Advanced fructo-oligosaccharides improve itching and aberrant epidermal lipid composition in children with atopic dermatitis.

Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined. Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks. Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p < 0.01) and maltose (p < 0.05 and p < 0.01). Sleep disturbance was improved only in the FOS group (p < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p < 0.01). Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD.

Postpartum Maternal Anxiety Affects the Development of Food Allergy Through Dietary and Gut Microbial Diversity During Early Infancy.

PURPOSE: We aimed to investigate the mediating factors between maternal anxiety and the development of food allergy (FA) in children until 2 years from birth. METHODS: In this longitudinal cohort of 122 mother-child dyads from pregnancy to 24 months of age, we regularly surveyed maternal psychological states, infant feeding data, and allergic symptoms and collected stool samples at 6 months of age for microbiome analysis. Considering the temporal order of data collection, we investigated serial mediating effects and indirect effects among maternal anxiety, dietary diversity (DD), gut microbial diversity, and FA using structural equation modeling. RESULTS: Among the 122 infants, 15 (12.3%) were diagnosed with FA. Increased maternal anxiety between 3 and 6 months after delivery was associated with a lower DD score. Infants with low DD at 4 months showed low gut microbial richness, which was associated with FA development. When the infants were grouped into 4 subtypes, using consensus clustering of 13 gut bacteria significantly associated with maternal anxiety and DD, Prevotella, Eubacterium, Clostridiales and Lachnospiraceae were more abundant in the group with lower FA occurrence. CONCLUSIONS: Postpartum maternal anxiety, mediated by reduced DD and gut microbial diversity, may be a risk factor for the development of FA in infants during the first 2 years of life.

Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) commonly occurs in children and can progress into severe phenotypes or atopic march, causing significant impairment in quality of life. It is important to find early biomarkers of future onset of AD before any clinical manifestations. OBJECTIVE: We sought to find early predictors of future onset of AD in skin stratum corneum (SC). METHODS: Skin tape strips were collected from the forearm of newborns (n = 111) with and without family history of atopic diseases at the age of 2 months before any signs of clinical AD. Children were clinically monitored until they reached age 2 years to ensure the presence or absence of AD. Skin tape strips were subjected to lipidomic analyses by the liquid chromatography electrospray ionization tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. RESULTS: Overall, 22 of 74 (29.7%) and 5 of 37 (13.5%) infants developed AD in the risk group and the control group, respectively. In the SC of future AD children, protein-bound ceramides were decreased (P < .001), whereas unsaturated sphingomyelin species (P < .0001) and "short-chain" nonhydroxy fatty acid sphingosine and alpha-hydroxy fatty acid sphingosine ceramides were elevated (P < .01 and .05, respectively) as compared with healthy children. Thymic stromal lymphopoietin and IL-13 levels were increased in the SC of future AD subjects (by 74.5% and 78.3%, P = .0022 and P < .0001, respectively). Multivariable logistic regression analysis revealed strong AD predicting power of the combination of family history, type 2 cytokines, and dysregulated lipids, with an odds ratio reaching 54.0 (95% CI, 9.2-317.5). CONCLUSIONS: Noninvasive skin tape strip analysis at age 2 months can identify asymptomatic children at risk of future AD development with a high probability.

Dietary Diversity during Early Infancy Increases Microbial Diversity and Prevents Egg Allergy in High-Risk Infants.

We aimed to investigate associations of dietary diversity (DD) with gut microbial diversity and the development of hen's egg allergy (HEA) in infants. We enrolled 68 infants in a high-risk group and 32 infants in a control group based on a family history of allergic diseases. All infants were followed from birth until 12 months of age. We collected infant feeding data, and DD was defined using 3 measures: the World Health Organization definition of minimum DD, food group diversity, and food allergen diversity. Gut microbiome profiles and expression of cytokines were evaluated by bacterial 16S rRNA sequencing and real-time reverse transcriptase-polymerase chain reaction. High DD scores at 3 and 4 months were associated with a lower risk of developing HEA in the high-risk group, but not in the control group. In the high-risk group, high DD scores at 3, 4, and 5 months of age were associated with an increase in Chao1 index at 6 months. We found that the gene expression of IL-4, IL-5, IL-6, and IL-8 were higher among infants who had lower DD scores compared to those who had higher DD scores in high-risk infants. Additionally, high-risk infants with a higher FAD score at 5 months of age showed a reduced gene expression of IL-13. Increasing DD within 6 months of life may increase gut microbial diversity, and thus reduce the development of HEA in infants with a family history of allergic diseases.

Exposure to cold airflow alters skin pH and epidermal filaggrin degradation products in children with atopic dermatitis.

BACKGROUND: We aimed to evaluate the influence of cold airflow from the air conditioner on skin barrier function and filaggrin degradation products (FDPs) in children with atopic deramtitis (AD). METHODS: In a case-control study, 28 children with AD and 12 normal children without AD were exposed to one of two air conditioner modes (conventional or wind-free) for 2 h. Skin temperature, transepidermal water loss (TEWL), and skin pH were measured on right cheek and forearm at pre- and post-exposure time points. We also measured filaggrin and FDPs from the volar surface of the forearm. RESULTS: In AD patients, skin temperature on the forearm decreased after exposure to the conventional and wind-free modes (P < 0.001 and P = 0.026), and TEWL on the cheek and the forearm decreased in the wind-free mode (P = 0.037 and 0.002). Skin pH on the cheek increased only after exposure to the conventional mode in AD group (P = 0.002). However, no changes in TEWL and skin pH were found after exposure to either the conventional or the wind-free mode in the control group. In AD children, the levels of pyrrolidone carboxylic acid (PCA) and cis-urocanic acid (UCA) were reduced only after exposure to the conventional mode (all P = 0.033). The percent changes of PCA and cis-UCA were higher in the AD group than those in the control group after exposure to conventional mode (P = 0.029 and 0.046). CONCLUSIONS: Skin barrier function in children with AD may be altered by the exposure to cold airflow from a conventional air conditioner.

Hepatic differentiation of human adipose tissue-derived mesenchymal stem cells and adverse effects of arsanilic acid and acetaminophen during in vitro hepatic developmental stage.

In the present study, we differentiated hepatocyte-like cells (HLCs) from human adipose tissue-derived mesenchymal stem cells (AT-MSCs). The hepatic differentiation was confirmed by increases in hepatic proteins or genes, the cytochrome P450 (CYP) activities, albumin secretion, and glycogen storage. To determine the developmental toxic effect of arsanilic acid (Ars) and acetaminophen (AAP) on the hepatic development, the differentiating cells were treated with the test chemicals (below IC12.5) from day 4 to day 13. The enzymatic activities of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) did not significantly differ in response to Ars treatment. AAP treatment increased the activities of all enzymes in a dose-dependent manner, significantly at concentrations of 2.5 and 5 mM of AAP. On the expressions of hepatic genes for Ars, the expressions were significantly inhibited by more than 0.5 mM for Albumin (ALB), but only 2.5 mM for α-feto protein (AFP). In the AAP-treated group, the expressions of ALB and AFP were significantly decreased at the concentrations exceeding 0.625 mM. The activities of CYP3A4 were not changed by both treatments. The activities of CYP1A2 were increased by AAP, whereas it was decreased by Ars treatment. In conclusion, AAP could cause serious adverse effects during the hepatic development as compared to Ars.