Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma

Tris (2-butoxyethyl) phosphate (TBEP) is an organophosphate flame retardant and used as a plasticizer in various household products such as plastics, floor polish, varnish, textiles, furniture, and electronic equipment. However, little is known about the effects of TBEP on the brain and behavior. We aimed to examine the effects of dietary exposure of TBEP on memory functions, their-related genes, and inflammatory molecular markers in the brain of allergic asthmatic mouse models. C3H/HeJSlc male mice were given diet containing TBEP (0.02 (TBEP-L), 0.2 (TBEP-M), or 2 (TBEP-H) μg/kg/day) and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. A novel object recognition test was conducted in each mouse at 11 weeks old. The hippocampi were collected to detect neurological, glia, and immunological molecular markers using the real-time RT-PCR method and immunohistochemical analyses. Mast cells and microglia were examined by toluidine blue staining and ionized calcium-binding adapter molecule (Iba)-1 immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of N-methyl-D aspartate receptor subunits Nr1 and Nr2b, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker Iba1, and astrocyte marker glial fibrillary acidic protein were significantly increased in TBEP-H-exposed mice with or without allergen. Microglia and mast cells activation were remarkable in TBEP-H-exposed allergic asthmatic mice. Our results indicate that chronic exposure to TBEP with or without allergen impaired object recognition ability accompanied with alteration of molecular expression of neuronal and glial markers and inflammatory markers in the hippocampus of mice. Neuron-glia-mast cells interaction may play a role in TBEP-induced neurobehavioral toxicity.

Dental Biofilm and Saliva Microbiome and Its Interplay with Pediatric Allergies

Little is known about the interplay and contribution of oral microorganisms to allergic diseases, especially in children. The aim of the clinical study was to associate saliva and dental biofilm microbiome with allergic disease, in particular with allergic asthma. In a single-center study, allergic/asthmatic children (n = 15; AA-Chd; age 10.7 ± 2.9), atopic/allergic children (n = 16; AT/AL-Chd; 11.3 ± 2.9), and healthy controls (n = 15; CON-Chd; age 9.9 ± 2.2) were recruited. After removing adhering biofilms from teeth and collecting saliva, microbiome was analyzed by using a 16s-rRNA gene-based next-generation sequencing in these two mediums. Microbiome structure differed significantly between saliva and dental biofilms (β-diversity). Within the groups, the dental biofilm microbiome of AA-Chd and AT/AL-Chd showed a similar microbial fingerprint characterized by only a small number of taxa that were enriched or depleted (4) compared to the CON-Chd, while both diseased groups showed a stronger microbial shift compared to CON-Chd, revealing 14 taxa in AA-Chd and 15 taxa in AT/AL-Chd that were different. This could be the first note to the contribution of dental biofilm and its metabolic activity to allergic health or disease.

Sensitivity in allergic asthmatic subjects towards house dust mite allergens

Asthma is a common problem that affects about 20 million peoples in India and can be often under-diagnosed or misdiagnosed. It can be allergic or non-allergic though the former type is more common and prevalent. Allergic asthma can be triggered by many allergens and house dust mites (HDM) are one of the common indoor allergens. The present study emphasizes the significance of house dust mites in allergic asthmatic subjects which is based on 115 asthmatic subjects in Punjab, India. For the quantification and the estimation of total serum Immunoglobulin E and HDM specific IgE, a mixture of 14 allergens and a mixture of two mite allergens viz. Dermatophagoides pteronyssinus and D. farinae were used respectively. Total and specific IgE levels were detected on ImmunoCAP Phadia 100. A statistically significant correlation between total and HDM specific IgE levels of 115 asthmatic subjects was found as compared to control group of 30 non-allergic individuals. The specific IgE levels of 54.78% subjects against the allergen of two mite species were found to be positive. Dust samples were taken from various localities of the houses to identify the diversity of house dust mites which were responsible for allergic asthma. Five common house dust mite species viz. D. pteronyssinus Trouessart, D. farinae Hughes, D. microceras Griffiths and Cunnington, D. aureliani Fain and Euroglyphus maynei Cooreman were identified from the dust. The present study observed that total IgE levels were higher with higher specific IgE levels against the mixture of two mite allergens viz. D. pteronyssinus and D. farinae in the blood serum. D. pteronyssinus was the most abundant and prevalent mite species followed by D. farinae. Therefore, present study concluded that HDM specific IgE levels against the mite allergen of D. pteronyssinus and D. farinae in the serum of allergic asthmatic subjects were found to be higher because of the higher prevalence of these two mites (D. pteronyssinus i.e. 69.80% and D. farinae i.e. 20.72%) in the house of allergic asthmatic subjects as compared to other identified mites.

A Multi-Omics Approach Reveals New Signatures in Obese Allergic Asthmatic Children

Background: Asthma is a multifactorial condition where patients with identical clinical diagnoses do not have the same clinical history or respond to treatment. This clinical heterogeneity is reflected in the definition of two main endotypes. We aimed to explore the metabolic and microbiota signatures that characterize the clinical allergic asthma phenotype in obese children. Methods: We used a multi-omics approach combining clinical data, plasma and fecal inflammatory biomarkers, metagenomics, and metabolomics data in a cohort of allergic asthmatic children. Results: We observed that the obese allergic asthmatic phenotype was markedly associated with higher levels of leptin and lower relative proportions of plasma acetate and a member from the Clostridiales order. Moreover, allergic children with a worse asthma outcome showed higher levels of large unstained cells, fecal D lactate and D/L lactate ratio, and with a higher relative proportion of plasma creatinine and an unclassified family member from the RF39 order belonging to the Mollicutes class. Otherwise, children with persistent asthma presented lower levels of plasma citrate and dimethylsulfone. Conclusion: Our integrative approach shows the molecular heterogeneity of the allergic asthma phenotype while highlighting the use of omics technologies to examine the clinical phenotype at a more holistic level.