Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study
Background: Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. Objective: To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. Methods: This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Results: Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non-IgE mediated in 15.5%, and mixed IgE/non-IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0-2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13-18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non-IgE-mediated FA in multivariate regression analysis. Conclusion: This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.
https://doi.org/10.2500/aap.2021.42.210005
Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.
Background: The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis; yet the immunologic mechanism of this strain's susceptibility is not known. Objective: We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain as both genes have been associated with food allergy. Methods: We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome and biomarkers of gut permeability. Results: In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis following oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring TLR4 or DOCK8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice when compared with C57BL/6 mice, which correlated with increased number of goblet cells in the small intestine. Conclusions: Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens and that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice.
https://doi.org/10.1016/j.jaci.2021.05.015
Accurate and reproducible diagnosis of peanut allergy using epitope mapping
Background: Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts. Methods: The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years. Results: In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%. Conclusions: In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing.
https://doi.org/10.1111/all.14905
A positive feedback loop reinforces the allergic immune response in human peanut allergy.
Food allergies are a leading cause of anaphylaxis, and cellular mechanisms involving antigen presentation likely play key roles in their pathogenesis. However, little is known about the response of specific antigen-presenting cell (APC) subsets to food allergens in the setting of food allergies. Here, we show that in peanut-allergic humans, peanut allergen drives the differentiation of CD209+ monocyte-derived dendritic cells (DCs) and CD23+ (FcєRII) myeloid dendritic cells through the action of allergen-specific CD4+ T cells. CD209+ DCs act reciprocally on the same peanut-specific CD4+ T cell population to reinforce Th2 cytokine expression in a positive feedback loop, which may explain the persistence of established food allergy. In support of this novel model, we show clinically that the initiation of oral immunotherapy (OIT) in peanut-allergic patients is associated with a decrease in CD209+ DCs, suggesting that breaking the cycle of positive feedback is associated with therapeutic effect.
https://doi.org/10.1084/jem.20201793
Increased Rates of Peanut and Tree Nut Aspiration as a Possible Consequence of Allergy Prevention by Early Introduction
Background: Pediatric airway foreign bodies (FBs) are a surgical emergency, and peanuts and tree nuts (PN/TNs) can pose a significant aspiration risk in young children. In 2015, the Learning Early About Peanut allergy (LEAP) trial established that early introduction of peanuts in high-risk infants reduced the risk of developing a peanut allergy. Infant feeding guidelines were subsequently modified to actively encourage the introduction of allergenic foods for all infants. The impact of this shift in feeding advice on the incidence of PN/TN inhalation has not been previously studied. Objective: To determine the incidence of PN/TN inhalation presentations to a quaternary pediatric hospital between 2008 and 2018. Methods: A retrospective cohort study of children who were diagnosed with an airway FB by rigid bronchoscopy. Results: There were 200 cases of FB inhalation (35% PN/TN, 34% other foods, and 31% inorganic material). There was a rise in the total incidence of FB inhalation over the study period (incidence ratio rate [IRR], 1.09; P < .001). The rise was due to PN/TN (IRR, 1.16; P < .002) and other food inhalation (IRR, 1.12; P = .01), with no significant increase in inorganic FB aspiration (IRR, 1; P = .94). Between pre-LEAP (2008-2014) and post-LEAP (2015-2018) periods, there was a trebling, doubling, and no increase in the rate of PN/TN, other food, and inorganic FB inhalation, respectively. Conclusions: Since the publication of the LEAP study, there has been a rise in PN/TN and other hard solid food inhalation at our institution. This study highlights the urgent need to engage the public to promote safe introduction of hard foods in young children.
https://doi.org/10.1016/j.jaip.2021.03.052
Legume Consumption and Gut Microbiome in Elderly Chinese Men and Women.
Background. Legumes, important components of a healthy diet, may exert their health benefits through the influence of the gut microbiome. However, this hypothesis has not been well investigated. Objective. This study aimed to examine the associations between long-term legume consumption and the gut microbiome among elderly Chinese. Methods. The gut microbiome was profiled by 16S ribosomal RNA sequencing in 2302 Chinese adults enrolled in 2 large cohort studies, the Shanghai Women's Health Study and Shanghai Men's Health Study. Legume consumption, including peanuts, soy foods, and other beans, was assessed by food-frequency questionnaires prior to the stool collection. The associations of legume consumption with microbiome diversity and taxa abundance were evaluated by linear or negative binomial hurdle models, adjusting for sociodemographics, lifestyle factors, and BMI. False discovery rate (FDR)–corrected P values (PFDR) < 0.1 were considered significant. Results. Respectively, 52% and 48% of study participants were male and female. The mean age at stool collection was 68.03 y for females and 70.28 y for males. Total legume consumption was not associated with gut microbiome ɑ-diversity; however, male peanut consumers had a higher Chao1 index (β = 22.52, P = 0.01), whereas peanut consumption was associated with decreased Shannon (β = −0.03, P = 0.02) and Simpson (β = −0.002, P = 0.04) indexes among females. In female and male combined analyses, total legume consumption was associated with increased Enterobacteriales (β = 0.30, PFDR = 0.06). Within this order, an unclassified genus in the family Enterobacteriaceae was positively associated with total legume (β = 0.46, PFDR = 0.03) and peanut (β = 0.59, PFDR = 0.01) consumption. Stratified analyses showed significant associations were primarily confined to females and participants without metabolic conditions. Conclusions. Legume consumption was associated with gut microbiome diversity and abundance of some bacteria in elderly Chinese. Associations were significant only among 1 sex group. Further research, including large-scale prospective studies and feeding trials, is needed to fully understand the role of the gut microbiome in legume–health associations.
https://doi.org/10.1093/jn/nxab139
Moderate walnut consumption improved lipid profile, steroid hormones and inflammation in trained elderly men: a pilot study with a randomized controlled trial
The present study aimed to investigate the effect of walnut consumption on lipid profile, steroid hormones and inflammation in trained elderly men performing concurrent (resistance and endurance) training. Twenty healthy elderly males were divided into two matched groups, in a randomized controlled trial, that trained three sessions per week: concurrent training + dietary walnut consumption (15 g/day for six weeks, CTW: n = 10); concurrent training + control diet (CT: n = 10). Fasting blood samples were taken 48 hours before and after intervention for biochemical assessments. levels of high-density lipoprotein (HDL) increased only in CTW compared to baseline (19.8%, p < 0.01). Total cholesterol (TC), low-density lipoprotein (LDL) and triglyceride (TG) levels significantly decreased only for CTW (i.e., 13%, 18%, and 18.5% at p < 0.01 for all). Testosterone (T) increased after the training compared to pre-training for CTW and CT (10.3%, p < 0.01, 4.27% p < 0.05, respectively), but the increase was significantly higher in CTW (p < 0.05). Serum cortisol (C) was lower for CTW compared to CT (p < 0.01). C-reactive protein (CRP) decreased in CTW in comparison with CT. The present study revealed that 6-week moderate walnut supplementation (15 g/day) improved lipid profile, steroid hormones and systematic inflammation in aged men performing concurrent training. These findings could be attributable to the potential effect of polyunsaturated fatty acids (PUFA) contained in walnut (linoleic acid, n-6; linolenic acid, n-3).
https://doi.org/10.5114/biolsport.2020.97676
Mediterranean diet enriched in extra-virgin olive oil or nuts modulates circulating exosomal non-coding RNAs.
Purpose. Exosomes are extracellular vesicles secreted by cells, which can transport different molecules, including nucleic acids. Dietary habits may induce gene regulation through the modulation of exosomal RNAs. We aimed at characterizing exosomal lncRNAs, mRNA and miRNAs modulation after a 1-year adherence to a low-fat diet (LFD) or to Mediterranean-based diets enriched in extra-virgin olive oil (MedDiet + EVOO) or in a mixture of nuts (MedDiet + Nuts). Methods. Plasma samples were collected, at baseline and after 1 year of dietary interventions, from 150 participants included in the PREDIMED study (Reus Center). LncRNAs, mRNAs and miRNAs were isolated from plasma exosomes and screened. RT-qPCR validation was performed for miRNAs. Results. Compared with LFD, 413 lncRNAs and 188 mRNAs, and 476 lncRNAs and 235 mRNAs were differentially modulated in response to the MedDiet + EVOO and MedDiet + Nuts interventions, respectively. In addition, after 1 year of dietary interventions, 26 circulating miRNAs were identified as differentially expressed between groups. After 1 year of intervention, 11 miRNAs significantly changed in LFD group, while 8 and 21 were modulated in response to the MedDiet enriched with EVOO or nuts, respectively. Bioinformatic analyses of differentially expressed miRNAs and their validated target genes suggest certain metabolic pathways are modulated by LFD (PI3K-Akt and AMPK), MedDiet + EVOO (PI3K-Akt, NF-kappa B, HIF-1, and insulin resistance), and MedDiet-Nuts (FoxO, PI3K-Akt, AMPK, p53 and HIF-1) interventions. Conclusion. Results show that 1-year MedDiet + Nuts and MedDiet + EVOO dietary interventions modulate exosomal RNA content, with the former affecting a higher number of miRNAs. The modulation of exosomal RNAs could help explain how the adherence to a Mediterranean diet may lead to beneficial effects and deserves further investigation.
https://doi.org/10.1007/s00394-021-02594-0
A Comprehensive Review of Almond Clinical Trials on Weight Measures, Metabolic Health Biomarkers and Outcomes, and the Gut Microbiota.
This comprehensive narrative review of 64 randomized controlled trials (RCTs) and 14 systematic reviews and/or meta-analyses provides an in-depth analysis of the effect of almonds on weight measures, metabolic health biomarkers and outcomes, and the colonic microbiota, with extensive use of figures and tables. Almonds are a higher energy-dense (ED) food that acts like a lower ED food when consumed. Recent systematic reviews and meta-analyses of nut RCTs showed that almonds were the only nut that had a small but significant decrease in both mean body mass and fat mass, compared to control diets. The biological mechanisms for almond weight control include enhanced displacement of other foods, decreased macronutrient bioavailability for a lower net metabolizable energy (ME), upregulation of acute signals for reduced hunger, and elevated satiety and increased resting energy expenditure. The intake of 42.5 g/day of almonds significantly lowered low-density lipoprotein cholesterol (LDL-C), 10-year Framingham estimated coronary heart disease (CHD) risk and associated cardiovascular disease (CVD) medical expenditures. Diastolic blood pressure (BP) was modestly but significantly lowered when almonds were consumed at >42.5 g/day or for >6 weeks. Recent RCTs suggest possible emerging health benefits for almonds such as enhanced cognitive performance, improved heart rate variability under mental stress, and reduced rate of facial skin aging from exposure to ultraviolet (UV) B radiation. Eight RCTs show that almonds can support colonic microbiota health by promoting microflora richness and diversity, increasing the ratio of symbiotic to pathogenic microflora, and concentrations of health-promoting colonic bioactives. Almonds are a premier healthy snack for precision nutrition diet plans
https://doi.org/10.3390/nu13061968
Dried Plum Consumption Improves Total Cholesterol and Antioxidant Capacity and Reduces Inflammation in Healthy Postmenopausal Women.
Dried plums contain bioactive components that have demonstrated antioxidant and anti-inflammatory effects. The objective of this study was to determine if dried plum consumption reduces the risk factors for cardiovascular disease (CVD) in postmenopausal women, specifically examining lipid profiles, oxidative stress, antioxidant capacity, and inflammation in a dose-dependent manner. We conducted a 6-month, parallel-design controlled clinical trial, where 48 postmenopausal women were randomly assigned to consume 0, 50, or 100 g of dried plum each day. After 6 months of intervention, total cholesterol (TC) in the 100 g/day treatment group (P = .002) and high-density lipoprotein cholesterol in the 50 g/day treatment group (P = .005) improved significantly compared to baseline. Inflammatory biomarkers interleukin-6 (P = .044) and tumor necrosis factor-α (P = .040) were significantly lower after 6 months within the 50 g/day dried plum group compared to baseline. Moreover, total antioxidant capacity increased significantly within the 50 g/day group (P = .046), and superoxide dismutase activity increased significantly within both 50 and 100 g/day groups (P = .044 and P = .027, respectively) after 6 months compared to baseline. In addition, plasma activities of alanine transaminase (P = .046), lactate dehydrogenase (P = .039), and creatine kinase (P = .030) were significantly lower after 6 months in the 50 g/day dried plum group. These findings suggest that daily consumption of 50-100 g dried plum improves CVD risk factors in postmenopausal women as exhibited by lower TC, oxidative stress, and inflammatory markers with no clear dose dependence.
https://doi.org/10.1089/jmf.2020.0142