The impact of high-salt diet on asthma in humans and mice: Effect on specific T-cell signatures and microbiome.

BACKGROUND: The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models. METHODS: Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24-h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite-induced allergic airway inflammation (AAI) fed with high-salt diet (HSD) or normal-salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach. RESULTS: In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD-fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2-TH17-biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung. CONCLUSIONS: High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD-induced T-cell lung profiles accompanied by alterations of gut and lung microbiome.

Accelerometry-assessed sleep clusters and cardiometabolic risk factors in adolescents.

OBJECTIVE: This study aimed to identify sleep clusters based on objective multidimensional sleep characteristics and test their associations with adolescent cardiometabolic health. METHODS: The authors included 1090 participants aged 14.3 to 16.4 years (mean = 15.2 years) who wore 7-day accelerometers during the 15-year follow-up of the German Infant Study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development (GINIplus) and the Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany (LISA) birth cohorts. K-means cluster analysis was performed across 12 sleep characteristics reflecting sleep quantity, quality, schedule, variability, and regularity. Cardiometabolic risk factors included fat mass index (FMI), blood pressure, triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and insulin resistance (n = 505). Linear and logistic regression models were examined. RESULTS: Five sleep clusters were identified: good sleep (n = 337); delayed sleep phase (n = 244); sleep irregularity and variability (n = 108); fragmented sleep (n = 313); and prolonged sleep latency (n = 88). The "prolonged sleep latency" cluster was associated with increased sex-scaled FMI (ß = 0.39, 95% CI: 0.15-0.62) compared with the "good sleep" cluster. The "sleep irregularity and variability" cluster was associated with increased odds of high triglycerides only in male individuals (odds ratio: 9.50, 95% CI: 3.22-28.07), but this finding was not confirmed in linear models. CONCLUSIONS: The prolonged sleep latency cluster was associated with higher FMI in adolescents, whereas the sleep irregularity and variability cluster was specifically linked to elevated triglycerides (≥1.7 mmol/L) in male individuals.

Dietary digestible carbohydrates are associated with higher prevalence of asthma in humans and with aggravated lung allergic inflammation in mice.

BACKGROUND: Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. METHODS: Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. RESULTS: We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. CONCLUSION: High consumption of digestible carbohydrates is associated with an increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms.

Novel Interactions of Myristic Acid and FADS3 Variants Predict Atopic Dermatitis among Indonesian Infants.

Fatty acids exert a range of different biological activities that could be relevant in the development of atopic dermatitis (AD). This study investigated the association of glycerophospholipid fatty acids (GPL-FA) with AD, and their interactions with single nucleotide polymorphisms (SNP) of the FADS1-3 gene cluster. Among 390 infants of the Indonesian ISADI study, GPL-FA were measured in umbilical plasma (P-0y) and in buccal cells at birth (B-0y), and again in buccal cells at AD onset or one year (B-1y). Prospective and cross-sectional associations with AD were assessed by logistic regression. Interactions of GPL-FA with 14 SNP were tested assuming an additive model. AD was diagnosed in 15.4% of participants. In B-1y, C18:2n-6 was inversely associated with AD; and positive associations were observed for C18:1n-9, C20:4n-6, C22:6n-3 and C20:4n-6/C18:2n-6. There were no prospective associations with AD, however, a significant interaction between the SNP rs174449 and B-0y C14:0 (myristic acid) was observed. This study indicates that Indonesian infants with AD have increased rates of endogenous long-chain polyunsaturated fatty acid production, as well as higher C18:1n-9 levels. GPL-FA measured at birth do not predict later AD incidence; however, genotype interactions reveal novel effects of myristic acid, which are modified by a FADS3 variant.

Association of Maternal Diet during Pregnancy and Metabolite Profile in Cord Blood.

Cord blood metabolites can be predictive of long-term disease risk, but how levels of different metabolites might vary with respect to maternal diet is not well understood. The aim of this study was to evaluate the associations of different dietary patterns during pregnancy with cord blood metabolites (including glycerophospholipid fatty acids, polar lipids, non-esterified fatty acids, amino acids, and the sum of hexoses). Participants from the German LISA birth cohort study, with available data on targeted cord blood metabolomics and maternal diet, were included (n = 739). Maternal diet during the last 4 weeks of pregnancy was assessed by a non-quantitative food-frequency questionnaire. Using factor analysis, ten dietary patterns were identified, which were used in linear regression models exploring associations with cord blood metabolites. After correction for multiple hypothesis testing and adjustment for basic covariates, "fish and shellfish" was associated with higher glycerophospholipid fatty acid C20:5 n3 and lower C22:5 n6, whereas the "meat and potato" pattern was directly associated with propionylcarnitine (C3:0). The observed associations highlight potential metabolic pathways involved in the early programming of health and disease through maternal diet, as well as the potential for establishing quantitative biomarkers for dietary patterns of pregnant women.

Obesogenic eating behaviour and dietary intake in German children and adolescents: results from the GINIplus and LISA birth cohort studies.

BACKGROUND/OBJECTIVES: The transition to adolescence is characterised by considerable behavioural changes, including diet. This study describes the level of obesogenic eating behaviours in 10- and 15-year-olds, and their association with dietary intake. SUBJECTS/METHODS: Participants of the 10- and 15-year follow-ups of the German GINIplus and LISA birth cohort studies were included (N10 = 2257; N15 = 1880). Eating behaviours and dietary intake were assessed via self-report questionnaires. Sex-stratified, cross-sectional associations of "external eating", "emotional eating" and "dietary restraint" (the latter at age 15 years only) with dietary intake (17 food groups-categorised into tertiles, macronutrients, and total energy) were assessed using multinomial logistic or multiple linear regression as required, adjusting for covariates and correcting for multiple testing. RESULTS: Reported levels of eating behaviours were low in both age-groups. External eating was higher in 10-year-old males than females, while all eating behaviours were most pronounced in 15-year-old females. At 10 years, emotional eating was associated with medium vegetable intake in females (Relative Risk Ratio (RRR) = 1.84, p = 0.0017). At 15 years, external eating was associated with total energy (kJ) in females (ß = 718, p = 0.0002) and high butter intake in males (RRR = 1.96, p = 0.0019). Dietary restraint in females was inversely associated with total energy (ß = -967, p < 0.0001) and omega-3 fatty acids (Means Ratio (MR) = 0.94, p = 0.0017), and positively associated with high fruit (RRR = 2.20, p = 0.0003) and whole grains (RRR = 1.94, p = 0.0013). CONCLUSION: Obesogenic eating behaviour scores are low among children and adolescents of a predominantly high socioeconomic status population and present only few associations with specific aspects of diet, mainly among adolescent females.

Association Study on Nutrition in the First Year of Life and Molar-Incisor Hypomineralization (MIH)-Results from the GINIplus and LISA Birth Cohort Studies.

Molar-incisor hypomineralization (MIH) is a condition with specific clinical presentation whose etiology to date still remains unknown. This study prospectively investigated the association between nutrition during the 1st year of life and the presence of MIH in the permanent dentition. Data from 1070 10-year-old children from two prospective birth cohort studies were included. Information on exclusive breastfeeding (EBF) and introduction of 48 food items into the child's diet was assessed at 4-, 6-, and 12-month time-points. Food diversity was defined according to the number of food items or food groups introduced into the child's diet and then subsequent categorization into low-, middle- and high-diversity groups was performed. MIH was scored in the permanent dentition at age of 10 years. The statistical analysis included logistic and Poisson hurdle regression models adjusted for potential confounders. EBF, food item and food group diversity at 4-, 6-, 12-month time-points were found to be non-significant in most of the categories for the development of MIH. However, significantly higher odds for the presence of MIH were found for certain categories. Despite the limitation of this study, such as arbitrary cut-offs for categorization of food items, the results of this study suggest the lack of an association between early nutrition in the first year of life and MIH in the permanent dentition.

Dietary saturated fat and low-grade inflammation modified by accelerometer-measured physical activity in adolescence: results from the GINIplus and LISA birth cohorts.

BACKGROUND: Saturated fatty acids (SFA) have been reported to promote inflammation. Nevertheless, evidence linking dietary SFA and low-grade inflammation in adolescents is scarce and inconsistent. The modulatory role of physical activity (PA) on fat metabolism and inflammation may provide a potential explanation. Thus, we assessed the association of dietary SFA with high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, in 15-year-olds, and evaluated possible interactions between dietary SFA and different levels of PA. METHODS: Children participating in the 15-year follow-ups of the GINIplus and LISA German birth cohort studies were included (N = 824). SFA intake was estimated by means of a food frequency questionnaire and PA recorded by accelerometers. Average daily minutes of PA were classified into "sedentary", "light" and "moderate-to-vigorous" (MVPA), using Freedson's cut-offs. HsCRP concentrations were measured in serum and categorized into 3 sex-specific levels (below detection limit (I), above 75th percentile (III), in between (II)). Sex-stratified cross-sectional associations between SFA and hsCRP were assessed using multinomial logistic regression, adjusting for potential confounders. Interaction terms were included between SFA and the different PA levels; and if significant interactions were observed, analyses stratified by tertiles of the relevant PA levels were performed. Relative risk ratios (RRR) and 95% confidence intervals (95%CI) were presented for a 1% increase in SFA. RESULTS: An inverse association was observed between SFA intake and hsCRP (II vs. I) in males (RRR = 0.85 [95%CI = 0.76;0.96], p = 0.008), whereas no significant association was observed in females. A significant interaction was observed with "sedentary" and "light" PA but not with MVPA in both sexes (p < 0.05). Stratified analyses indicated a significant inverse association between SFA and medium hsCRP levels in males in the highest light PA tertile (hsCRP II vs. I: 0.67 [0.517;0.858], p = 0.002). CONCLUSION: Our findings do not support a detrimental role of dietary SFA in low-grade inflammation among adolescents. In males, higher dietary SFA was associated with lower hsCRP, although this should be interpreted in the context of possibly correlated nutrients. Children spending the most time in light PA drove the observed inverse association, suggesting a synergistic effect of SFA and lifestyle PA in the resultant inflammatory response.

Association of Dietary Fatty Acids with Blood Lipids is Modified by Physical Activity in Adolescents: Results from the GINIplus and LISA Birth Cohort Studies.

The role of consuming different types of fatty acids (FA) at the expense of carbohydrates (CHO), on the blood lipid profile of adolescents is largely unknown, as is the modulating effect of different levels of physical activity (PA). Children from the GINIplus and LISA birth cohorts, with complete data on dietary FA (assessed by food-frequency questionnaires), objectively-measured PA (assessed by accelerometers) and blood lipids (lipoprotein cholesterol and triglycerides) at age 15 years, were included (N = 837). Sex-stratified associations between dietary FA and blood lipids were assessed by linear regression in substitution models which represented isocaloric replacements of CHO with saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (PUFA) or n-6 PUFA. To assess the interactions with PA, analyses were then performed stratified by tertiles of different PA levels (sedentary, lifestyle, moderate-to-vigorous (MVPA)). Both sexes presented a significant inverse association between MUFA and triglycerides, and females a direct association between n-3 PUFA and high-density lipoprotein. Stratifying by PA tertiles, associations were mainly restricted to participants with the lowest levels of lifestyle PA, or the highest time spent sedentary. The effects of dietary FA on the lipid profile vary in an activity-specific manner, emphasizing possible synergistic roles of diet and PA.