Translational Genomics in Legumes Allowed Placing In Silico 5460 Unigenes on the Pea Functional Map and Identified Candidate Genes in Pisum sativum L.

To identify genes involved in phenotypic traits, translational genomics from highly characterized model plants to poorly characterized crop plants provides a valuable source of markers to saturate a zone of interest as well as functionally characterized candidate genes. In this paper, an integrated view of the pea genetic map was developed. A series of gene markers were mapped and their best reciprocal homologs were identified on M. truncatula, L. japonicus, soybean, and poplar pseudomolecules. Based on the syntenic relationships uncovered between pea and M. truncatula, 5460 pea Unigenes were tentatively placed on the consensus map. A new bioinformatics tool, http://www.thelegumeportal.net/pea_mtr_translational_toolkit, was developed that allows, for any gene sequence, to search its putative position on the pea consensus map and hence to search for candidate genes among neighboring Unigenes. As an example, a promising candidate gene for the hypernodulation mutation nod3 in pea was proposed based on the map position of the likely homolog of Pub1, a M. truncatula gene involved in nodulation regulation. A broader view of pea genome evolution was obtained by revealing syntenic relationships between pea and sequenced genomes. Blocks of synteny were identified which gave new insights into the evolution of chromosome structure in Papillionoids and Eudicots. The power of the translational genomics approach was underlined

Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts.

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4th and 12th month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52-28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2-56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation

Continuous Rather Than Solely Early Farm Exposure Protects From Hay Fever Development

BACKGROUND: An important window of opportunity for early-life exposures has been proposed for the development of atopic eczema and asthma.OBJECTIVE: However, it is unknown whether hay fever with a peak incidence around late school age to adolescence is similarly determined very early in life.METHODS: In the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort potentially relevant exposures such as farm milk consumption and exposure to animal sheds were assessed at multiple time points from infancy to age 10.5 years and classified by repeated measure latent class analyses (n [ 769). Fecal samples at ages 2 and 12 months were sequenced by 16S rRNA. Hay fever was defined by parent -reported symptoms and/or physician's diagnosis of hay fever in the last 12 months using questionnaires at 10.5 years.RESULTS: Farm children had half the risk of hay fever at 10.5 years (adjusted odds ratio [aOR] 0.50; 95% CI 0.31-0.79) than that of nonfarm children. Whereas early life events such as gut microbiome richness at 12 months (aOR 0.66; 95% CI 0.46-0.96) and exposure to animal sheds in the first 3 years of life (aOR 0.26; 95% CI 0.06-1.15) were determinants of hay fever, the continuous consumption of farm milk from infancy up to school age was necessary to exert the protective effect (aOR 0.35; 95% CI 0.17-0.72).CONCLUSIONS: While early life events determine the risk of subsequent hay fever, continuous exposure is necessary to achieve protection. These findings argue against the notion that only early life exposures set long-lasting trajectories. (c) 2022 The Authors. Published by Elsevier IncPeer reviewe

Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma

Peer reviewedPostprin

An integrated molecular risk score early in life for subsequent childhood asthma risk.

BACKGROUND Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient-tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome-wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy). METHODS Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5-11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism-corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve-Bayes approach) combined with high-dimensional logistic regression models (LASSO). RESULTS Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism-corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5-6 years). CONCLUSION Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers

Cough without a cold in children : trajectories in the first ten years of life, association with allergic diseases and role of perinatal environment

La toux est un symptôme respiratoire fréquent et non spécifique chez l’enfant, habituellement présent uniquement durant une infection aigue des voies respiratoires. Cependant, certains enfants présentent une toux par excès de sensibilité se manifestant par des épisodes de toux fréquents ou récurrents, en dehors d’une infection, et des facteurs déclenchants habituellement non tussigènes. Bien qu’un des mécanismes étiologiques de cette hypersensibilité soit l’atopie, très peu d’études se sont intéressées à la relation entre trajectoires de toux dans l’enfance et maladies allergiques ainsi qu’à leur association avec l’environnement précoce.Afin d’identifier les trajectoires de toux dans l’enfance, d’analyser leur relation avec les maladies allergiques et avec l’environnement précoce, le travail de cette thèse a porté sur deux volets complémentaires : un volet épidémiologique observationnel chez l’enfant et un volet expérimental chez le lapin. Le volet épidémiologique reposait sur l’analyse des données de la cohorte prospective européenne PASTURE (Protection against Allergy: STUdy in Rural Environment). Parmi les 961 enfants inclus dans l’étude épidémiologique, une analyse en classes latentes a permis d’identifier cinq trajectoires de toux en dehors d’une infection : peu ou pas de symptômes (59,9 %), transitoire aigue (24,1 %), transitoire modérée (6,8 %), persistante à début tardif (4,8 %), et persistante à début précoce (4,4 %). En comparaison avec la trajectoire peu ou pas de symptômes, les autres trajectoires étaient significativement associées avec les sibilants, l’asthme et la rhinite allergique. La trajectoire persistante à début précoce avait la plus forte association pour l’asthme et était inversement associée à l’environnement fermier. L’allergie alimentaire était associée aux deux trajectoires persistantes. La sensibilisation atopique était associée uniquement à la toux persistante à début tardif. La consommation de lait de ferme bouilli durant la première année de vie était la seule exposition spécifique à l’environnement fermier significativement associée à une diminution du risque de toux persistante à début précoce et de toux transitoire aigue. Des infections respiratoires répétées ou prolongées dans la première année de vie étaient significativement associées à un risque plus élevé de toux persistante à début précoce. Le volet expérimental a permis d’évaluer l’impact de l’exposition périnatale à la poussière de ferme sur la sensibilité tussigène et la réactivité bronchique chez un modèle de lapin d’inflammation bronchique d’origine allergique. Un environnement spécifique a été appliqué aux lapines gestantes et à leurs lapereaux jusqu’à la sixième semaine de vie (zone exempte d’agent pathogène pour le groupe contrôle ; étable de veaux pour le groupe ferme). Les lapereaux étaient ensuite hébergés dans une zone conventionnelle de l’animalerie et sensibilisés à l’ovalbumine par voie intrapéritonéale. La sensibilité à la toux a été évaluée par la stimulation mécanique de la toux et la réactivité bronchique par un test à la méthacholine. Nous n’avons pas retrouvé d’effet de l’exposition précoce à une étable de veaux sur la sensibilité tussigène ni la réactivité bronchique.Nos résultats suggèrent un lien étroit entre toux persistante et pathologies atopiques ainsi que l’existence de potentiels facteurs de prévention communs. Les enfants présentant une toux persistante ou récurrente devraient être orientés vers un médecin allergologue pour qu’une évaluation allergologique complète soit réalisée. Les études de prévention des pathologies atopiques devraient également s’intéresser aux symptômes de toux en dehors d’une infection afin d’évaluer la pertinence de développer des stratégies de prévention communes.Cough is a frequent and non-specific respiratory symptom in children. In the majority of otherwise healthy children, cough is a symptom related to a self-limiting viral upper respiratory tract infection. However, some children have cough hypersensitivy that manifests as frequent or recurrent coughs, without a respiratory infection, and triggered by normally innocuous stimuli. Although atopy is one of the etiological mechanisms of this hypersensitivity, few studies has explored the relationship between cough trajectories in children and allergic diseases, as well as their association with early environment.In order to identify trajectories of cough in childhood, to analyse their relationship with allergic diseases and with early environment, the thesis work consisted of two complementary parts: an epidemiological observational part in children and an experimental part in rabbit. The epidemiological part was based on analysis of data from the prospective European birth cohort PASTURE (Protection against Allergy: STUdy in Rural Environment). Among the 961 children included in the epidemiological study, a latent class analysis allowed to identify five trajectories of cough without a cold: never of infrequent (59.9%), acute transient (24.1%), moderate transient (6.8%), late persistent (4.8%) and early persistent (4.4%). Compared with the never/infrequent trajectory, the other trajectories were significantly associated with wheezing, asthma and allergic rhinitis. Early persistent trajectory had the strongest association with asthma and was inversely associated with farm environment. Food allergy was associated with both persistent trajectories. Atopic sensitisation was only associated with the late persistent trajectory. Consumption of boiled farm milk during the first year of life was the only farm-specific exposure significantly associated with a decreased risk of early persistent cough and acute transient cough. Repeated or prolonged respiratory tract infections during the first year of life was associated with a higher risk of early persistent cough. The experimental part allowed to evaluate the impact of perinatal exposure to farm dust on cough sensitivity and airway responsiveness in an allergic airway inflammation rabbit model. A specific environment has been applied to pregnant rabbits and their offspring until six weeks after birth (pathogen-free zone for the control group, calf barn for the farm group). Rabbit pups were then housed in a conventional zone and sensitised to ovalbumin by intraperitoneal route. Cough sensitivity was assessed by mechanical stimulation of cough and airway responsiveness by a methacholine challenge. We did not find any effect of early exposure to the calf barn on cough sensitivity or bronchial reactivity.Our results suggest 1/ a close link between persistent cough and atopic diseases and 2/ the existence of potential common preventive factors. Children having persistent or recurrent cough should be referred to an allergist for a complete allergy assessment. Prevention studies for atopic diseases should also explored symptoms of cough without a cold in order to evaluate the relevance of developing common prevention strategies

Actualités en allergologie alimentaire et pédiatrique

International audienc

Evolution des prick-tests cutanés de l'âge de 1 an à 6 ans et relation avec la dermatite atopique et les IgE spécifiques (cohorte française de l'étude européenne PATURE (Protection contre l'Allergie : éTUde du milieu Rural et de son Environnement))

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Œsophagite à éosinophiles : le point sur les consensus de prise en charge

International audienc