Egg-sensitised infants have elevated CD4+ effector memory T regulatory cells from birth.

BACKGROUND: IgE-mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. METHODS: We performed detailed immune cell phenotyping of peripheral blood mononuclear cells and determined in vitro cytokine responses following allergen specific and non-specific immune stimulation. To determine if unique immune profiles were linked to early-life egg sensitisation, we compared 92 infants at 4-6 months of age, with (EggCAP+, n = 41) and without (EggCAP-, n = 51) early egg sensitisation. Additionally, 47 cord blood samples were analysed. For a subset of participants (n = 39), matching cord blood mononuclear cells were assessed by flow cytometry to establish the impact of IgE sensitisation on immune developmental trajectories. RESULTS: EggCAP+ infants were found to exhibit a unique immune phenotype characterised by increased levels of circulating CD4+ T regulatory cells (Treg), CD4+ effector memory (EM) Treg and increased expression of the IgE receptor, FcεR1, on basophils. The increased CD4+ EM Treg profiles were already present in cord blood samples from EggCAP+ infants. A general Th2-skewing of the immune system was observed based on increased IL-13 production following phytohemagglutinin stimulation and by comparing immune developmental trajectories, EggCAP+ infants displayed an expansion of basophils and reduced levels of CD4- T cells compared to EggCAP- infants. CONCLUSIONS: Immunological profiles associated with egg sensitisation are detectable in infant circulation at 4-6 months of age and at birth. Understanding the immune mechanisms underlying early-life sensitisation could provide important insights for future food allergy prevention strategies.

Feasibility and safety of introducing cashew nut spread in infant diets-A randomized trial.

BACKGROUND: To reduce peanut allergy prevalence, infant feeding guidelines now recommend introducing peanuts in an age-appropriate form (such as peanut butter) as part of complementary feeding. However, due to a lack of randomized trial evidence, most infant feeding and food allergy prevention guidelines do not include tree nuts. The aims of this trial were to determine safety and feasibility of dosage consumption recommendations for infant cashew nut spread introduction. METHODS: This is a parallel, three-arm (1:1:1 allocation), single-blinded (outcome assessors), randomized controlled trial. General population term infants were randomized at 6-8 months of age to either a one teaspoon (Intervention 1 n = 59) or increasing dosage regime of one teaspoon at 6-7 months, two teaspoons at 8-9 months, and three teaspoons from 10 months of age onwards (Intervention 2 n = 67) cashew nut spread, both three times per week, or no specific advice on cashew introduction (Control n = 70). At 1 year of age, food challenge proven IgE-mediated cashew nut allergy was assessed. RESULTS: Compliance in Intervention 1 (92%) was higher than Intervention 2 (79%), p = .04. Only one infant had delayed (at 5 h) facial swelling and eczema flare to cashew introduction at 6.5 months, but no cashew allergy at 1 year. Only one infant (Control) had cashew allergy at 1 year, and this infant had not been introduced to cashew prior to 12 months of age. CONCLUSION: Regular infant consumption of one teaspoon of cashew nut spread three times per week from 6 to 8 months of age was found to be feasible and safe.

Increasing emergency department visits for anaphylaxis in very early childhood: A canary in the coal mine.

AIM: The incidence of anaphylaxis is increasing globally in tandem with changing environmental and lifestyle factors. There is very limited data on very early childhood presentations. We aim to assess changes in rates, characteristics and management of infant anaphylaxis in a paediatric ED over a 15-year period. METHODS: We conducted a retrospective study of children <2 years of age who presented with verified anaphylaxis comparing cases in years 2003-2007 with those in 2013-2017. Standardised information was collected on demographics, clinical presentation, management and triggers. RESULTS: Manually confirmed anaphylaxis rates in <2 year olds increased from 3.6 to 6.2 per 104 population (OR 1.7, 95% CI: 1.3-2.7; p < 0.001) with the greatest increase in <1 year olds. Anaphylaxis severity increased between 2003-2007 and 2013-2017 (OR 2.3, 95% CI: 1.2-4.3; p = 0.018). Failure to administer adrenaline was reduced in 2013-2017 (p = 0.007). Food was the leading anaphylaxis trigger (97.85%). CONCLUSION: This is the first study to suggest an increase in the incidence and severity of ED anaphylaxis presentations in children aged <2 years. Increased awareness of specific characteristics in this age group is required to facilitate timely recognition and optimal management. Further large-scale studies are warranted to understand underlying environmental drivers and find prevention strategies to reduce the burden of disease.

Perinatal Women's Perspectives of, and Engagement in, Digital Emotional Well-Being Training: Mixed Methods Study.

BACKGROUND: Psychological distress in the early postpartum period can have long-lasting deleterious effects on a mother's well-being and negatively affect her infant's development. Intervention approaches based in contemplative practices such as mindfulness and loving-kindness and compassion are intended to alleviate distress and cultivate well-being and can be delivered effectively as digital mental health interventions (DMHIs). OBJECTIVE: To understand the feasibility of engaging perinatal women in digital interventions, this study aimed to document participants' experiences in the Mums Minds Matter (MMM) study, a pilot randomized controlled trial comparing mindfulness, loving-kindness and compassion, and progressive muscle relaxation training delivered in a digital format and undertaken during pregnancy. To assess the different stages of engagement during and after the intervention, we adapted the connect, attend, participate, enact (CAPE) framework that is based on the idea that individuals go through different stages of engagement before they are able to enact change. METHODS: The MMM study was nested within a longitudinal birth cohort, The ORIGINS Project. We aimed to recruit 25 participants per randomization arm. Data were collected sequentially during the intervention through regular web-based surveys over 8 weeks, with opportunities to provide regular feedback. In the postintervention phase, qualitative data were collected through purposive sampling. RESULTS: Of 310 eligible women, 84 (27.1% [connect rate]) enrolled to participate in MMM. Of the remaining 226 women who did not proceed to randomization, 223 (98.7%) failed to complete the baseline surveys and timed out of eligibility (after 30 weeks' gestation), and 3 (1.3%) displayed high psychological distress scores. Across all program groups, 17 (20% [attend rate]) of the 84 participants actively opted out, although more may have disengaged from the intervention but did not withdraw. The main reasons for withdrawal were busy life and other priorities. In this study, we assessed active engagement and ongoing skills use (participate and enact) through postintervention interviews. We undertook 15 participant interviews, conducted 1 month to 3 months after the intervention. Our results provide insights into participant barriers and enablers as well as app changes, such as the ability to choose topics, daily reminders, case studies, and diversity in sounds. Implementing a DMHI that is brief, includes frequent prompts or nudges, and is easily accessible is a key strategy to target perinatal women. CONCLUSIONS: Our research will enable future app designs that are sufficiently nuanced to maximize the uptake, engagement, and application of mental health skills and contemplative practices in the perinatal period. Providing convenient access to engaging and effective prevention programs is critical and should be part of prenatal self-care. Our research underscores the appeal and feasibility of digital intervention approaches based in contemplative practices for perinatal women. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) 12620000672954p; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000672954p. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19803.

Anti-Müllerian hormone concentration is associated with central adiposity and reproductive hormones in expectant fathers.

OBJECTIVE: The role of the anti-Müllerian hormone (AMH) as an indicator of physical and reproductive health in men is unclear. We assessed the relationships between AMH and follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and metabolic parameters, in a cohort of expectant fathers. DESIGN: ORIGINS Project prospective cohort study. SETTING: Community-dwelling men. PARTICIPANTS: Partners of pregnant women attending antenatal appointments. MAIN OUTCOME MEASURES: Serum AMH, FSH, LH, testosterone, and metabolic parameters. RESULTS: In 485 expectant fathers, median age 33 years, median AMH was 40 pmol/L (quartiles 29, 56). AMH was inversely correlated with FSH, age, and body mass index (BMI) (correlation coefficients: -.32, -.24, and -.17 respectively). The age association was nonlinear, with peak AMH between 20 and 30 years, a decline thereafter, and somewhat steady levels after 45 years. The inverse association of AMH with FSH was log-linear and independent of age and BMI (ß: -.07, SE: 0.01, p < .001). AMH was inversely correlated with waist circumference and directly associated with sex hormone-binding globulin. Testosterone was moderately correlated with AMH (correlation coefficient: .09, ß: .011, SE: 0.004, p = .014): this association was mediated by an inverse relationship with BMI (mediated proportion 0.49, p < .001). CONCLUSIONS: In reproductively active men, lower AMH is a biomarker for advancing age, and for poorer metabolic and reproductive health. The inverse association between AMH and FSH is independent of age and BMI, whereas the association of AMH and testosterone is mediated via BMI. The utility of AMH to predict reproductive and cardiometabolic outcomes in men warrants further investigation.

Exiting the Anthropocene: Achieving personal and planetary health in the 21st century.

Planetary health provides a perspective of ecological interdependence that connects the health and vitality of individuals, communities, and Earth's natural systems. It includes the social, political, and economic ecosystems that influence both individuals and whole societies. In an era of interconnected grand challenges threatening health of all systems at all scales, planetary health provides a framework for cross-sectoral collaboration and unified systems approaches to solutions. The field of allergy is at the forefront of these efforts. Allergic conditions are a sentinel measure of environmental impact on human health in early life-illuminating how ecological changes affect immune development and predispose to a wider range of inflammatory noncommunicable diseases (NCDs). This shows how adverse macroscale ecology in the Anthropocene penetrates to the molecular level of personal and microscale ecology, including the microbial systems at the foundations of all ecosystems. It provides the basis for more integrated efforts to address widespread environmental degradation and adverse effects of maladaptive urbanization, food systems, lifestyle behaviors, and socioeconomic disadvantage. Nature-based solutions and efforts to improve nature-relatedness are crucial for restoring symbiosis, balance, and mutualism in every sense, recognizing that both personal lifestyle choices and collective structural actions are needed in tandem. Ultimately, meaningful ecological approaches will depend on placing greater emphasis on psychological and cultural dimensions such as mindfulness, values, and moral wisdom to ensure a sustainable and resilient future.

Understanding Engagement in Digital Mental Health and Well-being Programs for Women in the Perinatal Period: Systematic Review Without Meta-analysis.

BACKGROUND: Pregnancy and the postnatal period can be a time of increased psychological distress, which can be detrimental to both the mother and the developing child. Digital interventions are cost-effective and accessible tools to support positive mental health in women during the perinatal period. Although studies report efficacy, a key concern regarding web-based interventions is the lack of engagement leading to drop out, lack of participation, or reduced potential intervention benefits. OBJECTIVE: This systematic review aimed to understand the reporting and levels of engagement in studies of digital psychological mental health or well-being interventions administered during the perinatal period. Specific objectives were to understand how studies report engagement across 4 domains specified in the Connect, Attend, Participate, and Enact (CAPE) model, make recommendations on best practices to report engagement in digital mental health interventions (DMHIs), and understand levels of engagement in intervention studies in this area. To maximize the utility of this systematic review, we intended to develop practical tools for public health use: to develop a logic model to reference the theory of change, evaluate the studies using the CAPE framework, and develop a guide for future data collection to enable consistent reporting in digital interventions. METHODS: This systematic review used the Cochrane Synthesis Without Meta-analysis reporting guidelines. This study aimed to identify studies reporting DMHIs delivered during the perinatal period in women with subclinical mood symptoms. A systematic database search was used to identify relevant papers using the Ovid Platform for MEDLINE, PsycINFO, EMBASE, Scopus, Web of Science, and Medical Subject Headings on Demand for all English-language articles published in the past 10 years. RESULTS: Searches generated a database of 3473 potentially eligible studies, with a final selection of 16 (0.46%) studies grouped by study design. Participant engagement was evaluated using the CAPE framework and comparable variables were described. All studies reported at least one engagement metric. However, the measures used were inconsistent, which may have contributed to the wide-ranging results. There was insufficient reporting for enactment (ie, participants' real-world use of intervention skills), with only 38% (6/16) of studies clearly recording longer-term practice through postintervention interviews. The logic model proposes ways of conceptualizing and reporting engagement details in DMHIs more consistently in the future. CONCLUSIONS: The perinatal period is the optimal time to intervene with strength-based digital tools to build positive mental health. Despite the growing number of studies on digital interventions, few robustly explore engagement, and there is limited evidence of long-term skill use beyond the intervention period. Our results indicate variability in the reporting of both short- and long-term participant engagement behaviors, and we recommend the adoption of standardized reporting metrics in future digital interventions. TRIAL REGISTRATION: PROSPERO CRD42020162283; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=162283.

Longitudinal egg-specific regulatory T- and B-cell development: Insights from primary prevention clinical trials examining the timing of egg introduction.

BACKGROUND: Egg allergy affects almost 1 in 10 Australian infants. Early egg introduction has been associated with a reduced risk in developing egg allergy; however, the immune mechanisms underlying this protection remain unclear. OBJECTIVE: To examine the role of regulatory immune cells in tolerance induction during early egg introduction. METHODS: Cryopreserved peripheral blood mononuclear cells (PBMC) were obtained from infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy; BEAT (at 12 months, n = 42) and STEP (at 5 months n = 82; 12 months n = 82) study cohorts. In vitro ovalbumin-stimulated PBMC were analyzed by flow cytometry for presence of ovalbumin-specific regulatory T cells, using activation markers, FoxP3, and IL-10 expression. Ovalbumin-specific regulatory B cells were identified by co-expression of fluorescence-conjugated ovalbumin and IL-10. RESULTS: Specific, age-dependent expansion of ovalbumin-specific regulatory T cells was only observed in infants who (a) had early egg introduction and (b) did not have egg allergy at 12 months. This expansion was blunted or impaired in children who did not undergo early egg introduction and in those with clinical egg allergy at 12 months. Infants with egg allergy at 12 months of age also had reduced frequency of ovalbumin-specific regulatory B cells compared to egg-tolerant infants. CONCLUSION: Early egg introduction and clinical tolerance to egg were associated with expansion of ovalbumin-specific T and B regulatory cells, which may be an important developmental process for tolerance acquisition to food allergens.

Maternal Late-Pregnancy Serum Unmetabolized Folic Acid Concentrations Are Not Associated with Infant Allergic Disease: A Prospective Cohort Study.

BACKGROUND: The increase in childhood allergic disease in recent decades has coincided with increased folic acid intakes during pregnancy. Circulating unmetabolized folic acid (UMFA) has been proposed as a biomarker of excessive folic acid intake. OBJECTIVE: We aimed to determine if late-pregnancy serum UMFA and total folate concentrations were associated with allergic disease risk in the offspring at 1 y of age in a population at high risk of allergy. METHODS: The cohort consisted of 561 mother-infant pairs from Western Australia. To be eligible the infant had to have a first-degree relative (mother, father, or sibling) with a history of medically diagnosed allergic disease. Maternal venous blood was collected between 36 and 40 wk of gestation. Serum UMFA was measured by LC-tandem MS. Serum total folate was determined using a microbiological method with chloramphenicol-resistant Lactobacillus rhamnosus as the test organism, and was collected between 36 and 40 wk of gestation. UMFA concentrations were measured by tandem MS using stable isotope dilution; folate concentrations were determined using the microbiological method with standardized kits. Infant allergic disease outcomes of medically diagnosed eczema, steroid-treated eczema, atopic eczema, IgE-mediated food allergy, allergen sensitization, and medically diagnosed wheeze were assessed at 1 y of age. RESULTS: Median (IQR) concentrations for UMFA and serum folate were 1.6 (0.6-4.7) and 53.2 (32.6-74.5) nmol/L, respectively. Of the infants, 34.6% had medically diagnosed eczema, 26.4% allergen sensitization, and 14.9% had an IgE-mediated food allergy. In both adjusted and unadjusted models there was little evidence of association between UMFA or serum folate and any of the infant allergy outcomes. CONCLUSIONS: In this cohort of children at high risk of allergic disease there was no association between maternal UMFA or serum folate concentrations measured in late pregnancy and allergic disease outcomes at 1 y of age.

Lower Cord Blood IL-17 and IL-25, but Not Other Epithelial Cell-Derived Cytokines Are Associated with Atopic Dermatitis in Infancy.

BACKGROUND: There is a growing need for early biomarkers that may predict the development of atopic dermatitis (AD). As alterations in skin barrier may be a primary event in disease pathogenesis, epithelial cell (EC) cytokines expression patterns may be a potential biomarker in early life to target allergy preventive strategies towards "at-risk" infants. OBJECTIVES: The aim of this longitudinal investigation was to examine from birth over the course of infancy levels of the EC cytokines: thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, IL-25, and IL-17 in infants at high-risk of AD due to maternal atopy. METHOD: We collected (n = 31) cord blood samples from atopic mothers and followed up their infants at 4-6 and 12 months of age for collection of peripheral venous blood samples and diagnosis of AD. TSLP concentration was measured by ELISA after acetone precipitation of the samples. IL-33, IL-25, and IL-17 levels were measured by Luminex. RESULTS: Seven infants who developed AD had lower levels of IL-25 and IL-17 at birth compared to the 24 infants who did not develop AD by 12 months of age. CONCLUSIONS: Lower cord blood levels of IL-17 and IL-25, but not other EC cytokines, were associated with the onset of AD during infancy. Our results highlight that the in-utero period appears critical, and potential maternal influences on cord blood EC-derived cytokine concentrations requires further exploration.

Developmental Origins of Health and Disease (DOHaD): The importance of life-course and transgenerational approaches.

With well-established evidence that early life conditions have a profound influence on lifespan and health-span, new interventional birth cohorts are examining ways to optimise health potential of individuals and communities. These are aimed at going beyond preventing disease, to the conditions that facilitate flourishing from an early age. Covering diverse domains, local community projects, such as The ORIGINS Project, are taking a broader approach to the protective and buffering factors that enhance resilience and reduce allostatic load, such as building nature relatedness, interpersonal relationships, mindfulness, and positive emotions. Such cohorts aim to address how 'upstream' approaches will have flow on effects to the 'historical' risk targets (such as poor nutrition, physical inactivity, and stress) by influencing these core behaviours through better relationships with self, community, and the environment. In addition to scientific pursuit, interventional cohorts can contribute to solutions ineverycommunity - nourishing individuals and communities towards positive change.

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

BACKGROUND: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 µg, daily epicutaneous peanut protein; DBV712 250 µg). OBJECTIVE: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. METHODS: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 µg, subjects who had received DBV712 250 µg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. RESULTS: Of 213 eligible subjects who had received DBV712 250 µg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). CONCLUSIONS: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

A world of inflammation: the need for ecological solutions that co-benefit people, place and planet.

The ecology of the early environment - including microbial diversity, nutrition, nature, social interactions and the totality of exposures in the wider "exposome" - have life-long implications for all aspects of health and resilience. In particular, the emergence of "microbiome science" provides new evidence for vital relationships between biodiversity and health at every level. New perspectives of ecological interdependence connect personal and planetary health; the human health crisis cannot be separated from the social, political and economic "ecosystems" otherwise driving dysbiosis (from its etymological root, "life in distress") at every level. Adverse changes in macroscale ecology - of food systems, lifestyle behaviours, socioeconomic disadvantage and environmental degradation - all impact the microbial systems sitting at the foundations of all ecosystems. In particular, changes in the function and composition of the human-associated microbiome have been implicated in the mounting global burden of noncommunicable diseases (NCDs), exacerbating inflammation and metabolic dysregulation through multiple pathways across the lifespan. This "dysbiotic drift" (adverse shifts in ecology at all scales) underscores the need for ecological approaches aimed at restoring symbiosis, balance and mutualism. While there is promise with supplement-based strategies (e.g. probiotics, prebiotics), it is essential to focus on upstream factors implicated in dysbiosis, including the health of wider environments, lifestyle, nature relatedness, and the social policies and practices which can facilitate or inhibit dysbiotic drift. This also calls for ambitious integrative approaches which not only define these interconnections, but also capitalize on them to create novel, collaborative and mutualistic solutions to our vast interdependent global challenges.

L'écologie de l'environnement précoce - comprenant diversité microbienne, nutrition, nature, interactions sociales et totalité des expositions du large « exposome ¼ - a des implications tout au long de la vie pour tous les aspects de la santé et de la résilience. En particulier, l'émergence de « la science du microbiome ¼ fournit de nouvelles preuves pour les relations vitales entre biodiversité et santé à tous les niveaux. De nouvelles perspectives d'interdépendance écologique connectent la santé personnelle et planétaire ; la crise de la santé humaine ne peut être séparée des écosystèmes économique, politique et social à moins de mener à la dysbiose (de son origine étymologique « vie en péril ¼) à tous les niveaux. Les changements indésirables de l'écologie à grande échelle - systèmes alimentaires, comportement de style de vie, désavantages socio-économiques et dégradation environnementale - impactent tous les systèmes microbiens siégeant à la base de tous les écosystèmes. En particulier, les changements de fonction et de composition du microbiome associé à l'homme ont été impliqués dans l'augmentation de la charge globale des maladies non transmissibles (NCDs), exacerbant l'inflammation et la dérégulation du métabolisme à travers de multiples voies au cours de la vie. Cette « dérive de dysbiose ¼ (dérives indésirables de l'écologie à tous les niveaux) sous-estime le besoin des approches écologiques objectivant la restauration symbiose, balance et mutualisme. Alors que des stratégies supplémentaires sont prometteuses (ex : probiotiques, prébiotiques), il est essentiel de focaliser sur des facteurs en amont impliqués dans la dysbiose, comprenant : santé d'environnements plus larges, style de vie, nature de la parenté, et pratiques sociales, qui peuvent faciliter ou inhiber la dérive de dysbiose. Ceci appel aussi des approches qui ne définissent pas seulement ces interconnections mais aussi capitalisent sur elles pur créer des solutions nouvelles, collaboratives et mutualistes pour nos vastes défis globaux interdépendants.

La ecología del medio ambiente temprano -incluida la diversidad microbiana, la nutrición, la naturaleza, las interacciones sociales y la totalidad de las exposiciones en toda la amplitud del "exposoma"- tiene implicaciones de por vida para todos los aspectos de la salud y la resiliencia. En particular, el surgimiento de la "ciencia del microbioma" proporciona nueva evidencia de las relaciones vitales entre la biodiversidad y la salud en todos los niveles. Nuevas perspectivas de interdependencia ecológica conectan la salud personal y planetaria; la crisis de la salud humana no puede separarse de los "ecosistemas" sociales, políticos y económicos que de otro modo conducen a la disbiosis (de su raíz etimológica, "vida alterada") en todos los niveles. Los cambios adversos en la ecología a macroescala (de los sistemas alimentarios, los comportamientos de estilo de vida, las desventajas socioeconómicas y la degradación ambiental) tienen un impacto en los sistemas microbianos que se encuentran en los cimientos de todos los ecosistemas. En particular, los cambios en la función y composición del microbioma asociado a los seres humanos se han visto implicados en la creciente carga mundial de enfermedades no transmisibles (ENT), que exacerban la inflamación y la disregulación metabólica a través de múltiples vías a lo largo de la vida. Esta "deriva disbiótica" (cambios adversos en la ecología a todas las escalas) subraya la necesidad de enfoques ecológicos destinados a restaurar la simbiosis, el equilibrio y el mutualismo. Si bien es prometedor con las estrategias basadas en suplementos (por ejemplo, probióticos, prebióticos), es esencial centrarse en los factores anteriores implicados en la disbiosis, incluida la salud de entornos más amplios, el estilo de vida, la relación con la naturaleza y las políticas y prácticas sociales que pueden facilitar o inhibir la deriva disbiótica. Esto también requiere enfoques integradores ambiciosos que no solo definan estas interconexiones, sino que también las aprovechen para crear soluciones novedosas, colaborativas y mutualistas para nuestros vastos desafíos globales interdependientes.

A ecologia do ambiente inicial - incluindo diversidade microbiana, nutrição, natureza, interações sociais e a totalidade das exposições no "exposome" mais amplo - tem implicações ao longo da vida para todos os aspectos da saúde e resiliência. Em particular, o surgimento da "ciência do microbioma" fornece novas evidências para relações vitais entre a biodiversidade e a saúde em todos os níveis. Novas perspectivas de interdependência ecológica conectam a saúde pessoal e planetária; a crise da saúde humana não pode ser separada dos "ecossistemas" social, político e econômico, levando à disbiose (de sua raiz etimológica, "vida em perigo") em todos os níveis. Mudanças adversas na ecologia da macroescala - de sistemas alimentares, hábitos de vida, desvantagem socioeconômica e degradação ambiental - impactam os sistemas microbianos que estão na base de todos os ecossistemas. Em particular, as mudanças na função e na composição do microbioma associado ao ser humano têm sido implicadas no aumento da carga global de doenças não comunicáveis (DNCs), exacerbando a inflamação e a desregulação metabólica por meio de várias vias ao longo da vida. Esta "deriva disbiótica" (mudanças adversas na ecologia em todas as escalas) ressalta a necessidade de abordagens ecológicas destinadas a restaurar a simbiose, o equilíbrio e o mutualismo. Embora as estratégias baseadas em suplementos (por exemplo, probióticos, prebióticos) sejam uma grande promessa, é essencial focar nos fatores desencadeadores relacionados à disbiose, incluindo a saúde de forma geral, estilo de vida, relacionamento com a natureza e as políticas e práticas sociais que podem facilitar ou inibir a deriva disbiótica. Isso também exige abordagens integrativas ambiciosas que não apenas definam essas interconexões, mas também as capitalizem para criar soluções novas, colaborativas e mutualísticas para nossos desafios globais vastos e interdependentes.

Cord Blood T Cells Expressing High and Low PKCζ Levels Develop into Cells with a Propensity to Display Th1 and Th9 Cytokine Profiles, Respectively.

Low Protein Kinase C zeta (PKCζ) levels in cord blood T cells (CBTC) have been shown to correlate with the development of allergic sensitization in childhood. However, little is known about the mechanisms responsible. We have examined the relationship between the expression of different levels of PKCζ in CBTC and their development into mature T cell cytokine producers that relate to allergy or anti-allergy promoting cells. Maturation of naïve CBTC was initiated with anti-CD3/-CD28 antibodies and recombinant human interleukin-2 (rhIL-2). To stimulate lymphocyte proliferation and cytokine production the cells were treated with Phytohaemagglutinin (PHA) and Phorbol myristate acetate (PMA). Irrespective of the PKCζ levels expressed, immature CBTC showed no difference in lymphocyte proliferation and the production of T helper 2 (Th2) cytokine interleukin-4 (IL-4) and Th1 cytokine, interferon-gamma (IFN-γ), and influenced neither their maturation from CD45RA+ to CD45RO+ cells nor cell viability/apoptosis. However, upon maturation the low PKCζ expressing cells produced low levels of the Th1 cytokines, IFN-γ, IL-2 and tumour necrosis factor-alpha (TNF), no changes to levels of the Th2 cytokines, IL-4, IL-5 and IL-13, and an increase in the Th9 cytokine, IL-9. Other cytokines, lymphotoxin-α (LT-α), IL-10, IL-17, IL-21, IL-22 and Transforming growth factor-beta (TGF-ß) were not significantly different. The findings support the view that low CBTC PKCζ levels relate to the increased risk of developing allergic diseases.

Characterization of the Transient Deficiency of PKC Isozyme Levels in Immature Cord Blood T Cells and Its Connection to Anti-Allergic Cytokine Profiles of the Matured Cells.

Cord blood T cells (CBTC) from a proportion of newborns express low/deficient levels of some protein kinase C (PKC) isozymes, with low levels of PKCζ correlating with increased risk of developing allergy and associated decrease in interferon-gamma (IFN-γ) producing T cells. Interestingly, these lower levels of PKCζ were increased/normalized by supplementing women during pregnancy with n-3 polyunsaturated fatty acids. However, at present, we have little understanding of the transient nature of the deficiency in the neonate and how PKCζ relates to other PKC isozymes and whether their levels influence maturation into IFN-γ producing T cells. There is also no information on PKCζ isozyme levels in the T cell subpopulations, CD4+ and CD8+ cells. These issues were addressed in the present study using a classical culture model of neonatal T cell maturation, initiated with phytohaemagglutinin (PHA) and recombinant human interleukin-2 (rhIL-2). Of the isozymes evaluated, PKCζ, ß2, δ, µ, ε, θ and λ/ι were low in CBTCs. The PKC isozyme deficiencies were also found in the CD4+ and CD8+ T cell subset levels of the PKC isozymes correlated between the two subpopulations. Examination of changes in the PKC isozymes in these deficient cells following addition of maturation signals showed a significant increase in expression within the first few hours for PKCζ, ß2 and µ, and 1-2 days for PKCδ, ε, θ and λ/ι. Only CBTC PKCζ isozyme levels correlated with cytokine production, with a positive correlation with IFN-γ, interleukin (IL)-2 and tumour necrosis factor-alpha (TNF), and a negative association with IL-9 and IL-10. The findings reinforce the specificity in using CBTC PKCζ levels as a biomarker for risk of allergy development and identify a period in which this can be potentially 'corrected' after birth.

In infants with sufficient vitamin D status at birth, vitamin D supplementation does not impact immune development.

BACKGROUND: Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. METHOD: A double-blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. RESULTS: Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P = .002) and 87.5 vs 77 nmol/L at 6 months of age (P = .08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4- T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months. CONCLUSIONS: Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema.

Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up.

Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.

A butterfly flaps its wings: Extinction of biological experience and the origins of allergy.

OBJECTIVE: To explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation. DATA SOURCES: PubMed and Web of Science were searched using the keywords biodiversity, nature relatedness, allergic disease, microbiome, noncommunicable diseases, coronavirus disease 2019, and associated terms. STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity. RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects against allergy and both acute and chronic inflammatory disorders. These important links to ecopsychological constructs of the extinction of experience, which indicates that loss of direct, personal contact with biodiversity (wildlife and the more visible elements of the natural world), might lead to emotional apathy and irresponsible behaviors toward the environment. CONCLUSION: The immune system is a useful early barometer of environmental effects and, by means of the microbiome, is a measure of the way in which our current experiences differ from our ancestral past. Although we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspects of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, and physical activity and promote environmental responsibility.

Evaluating Engagement in a Digital and Dietetic Intervention Promoting Healthy Weight Gain in Pregnancy: Mixed Methods Study.

BACKGROUND: Early excess and inadequate gestational weight gain (GWG) have been associated with negative outcomes for mother and child. The use of digital media to deliver pregnancy lifestyle interventions is increasing, but there is little data on participant engagement. The Pregnancy Lifestyle Activity and Nutrition (PLAN) intervention pilot study was an electronic health and dietetic-delivered intervention program promoting healthy GWG in early pregnancy. OBJECTIVE: This study aims to explore the interactions of participants with the program and to assess its acceptability. METHODS: This study uses both quantitative and qualitative methods using data from parent randomized controlled trial (ACTRN12617000725369). Quantitative data from 22 participants in the intervention arm who completed the study provided measures of the interactions participants had with the digital components of the program and with dietetic consultations. A descriptive qualitative analysis employed semistructured interviews with 9 participants to elicit views on the acceptability of the intervention and its components. RESULTS: The electronic delivery of information and recording of weight from 8 to 20 weeks of gestation were universally accepted. Component (face-to-face dietitian, weight tracker, website information delivery, and SMS goal prompting) acceptability and engagement differed between individuals. A total of 4 key themes emerged from the qualitative analysis: supporting lifestyle change, component acceptability and value, delivery platforms, and engagement barriers. CONCLUSIONS: The PLAN intervention and its delivery via a blend of personal dietetic consultations and digital program delivery was found to be acceptable and valuable to pregnant women. Individuals responded differently to various components, emphasizing the importance of including women in the development of lifestyle interventions and allowing participants to choose and tailor programs. Larger randomized controlled trials using these insights in a broader section of the community are needed to inform the iterative development of practical, time-efficient, and cost-effective ways of supporting optimal GWG with the potential to optimize outcomes for pregnant women and their child.

Direct infant UV light exposure is associated with eczema and immune development.

BACKGROUND: Suboptimal vitamin D levels during critical periods of immune development have emerged as an explanation for higher rates of allergic diseases associated with industrialization and residing at higher latitudes. OBJECTIVE: We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development. METHODS: By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age. RESULTS: At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D-supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter [J/m2; interquartile range, 322-1210 J/m2]) compared with those without eczema (median, 998 J/m2 [interquartile range, 676-1577 J/m2]; P = .02). UV light exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like receptor ligands. CONCLUSION: This study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.