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Understanding modifiable prenatal and early life causal determinants of food allergy is important for the prevention of the disease. Randomized clinical trials studying environmental and dietary determinants of food allergy may not always be feasible. Identifying risk/protective factors for early‐life food allergy often relies on observational studies, which may be affected by confounding bias. The directed acyclic graph (DAG) is a causal diagram useful to guide causal inference from observational epidemiological research. To date, research on food allergy has made little use of this promising method. We performed a literature review of existing evidence with a systematic search, synthesized 32 known risk/protective factors, and constructed a comprehensive DAG for early‐life food allergy development. We present an easy‐to‐use online tool for researchers to re‐construct, amend, and modify the DAG along with a user's guide to minimize confounding bias. We estimated that adjustment strategies in 57% of previous observational studies on modifiable factors of childhood food allergy could be improved if the researchers determined their adjustment sets by DAG. Future researchers who are interested in the causal inference of food allergy development in early life can apply the DAG to identify covariates that should and should not be controlled in observational studies. [ABSTRACT FROM AUTHOR]

Exposure to infectious diseases in early life has been linked to increased mortality risk in later life in high-disease settings, such as eighteenth- and nineteenth-century Europe. Less is known about the long-term effects of early-life disease exposure in milder disease environments. This study estimates heterogeneous effects from disease exposure in infancy on later-life mortality in twentieth-century Sweden, by socioeconomic status at birth and sex. Using historical population data for southern Sweden, we study 11,515 individuals who were born in 1905–1929 from age 1 until age 85. We measure exposure to disease using the local post–early neonatal mortality rate in the first 12 months after birth and apply flexible parametric survival models. For females, we find a negative effect on life expectancy (scarring) at ages 1–85 following high disease exposure in infancy, particularly for those born to unskilled workers. For males, we find no negative effect on later-life survival, likely because stronger mortality selection in infancy outweighs scarring. Thus, even as the incidence of infectious diseases declined at the start of the twentieth century, early-life disease exposure generated long-lasting negative but heterogeneous population health effects. [ABSTRACT FROM AUTHOR]

With the global prevalence of allergic disease continuing to rise at an alarming rate, the need for effective and safe therapeutics is paramount. Given the critical role of the early-life microbiota on immune development, emerging research suggests the potential use of live biotherapeutic products (LBP) for the prevention and treatment of childhood allergy. However, findings are limited and inconsistent. Therefore, the present review critically evaluates the current animal and human data on the therapeutic value of LBPs in allergy, the underlying immunological mechanisms by which LBPs may mediate allergy susceptibility, limitations of the current research that need to be addressed, and future research directions. Accordingly, LBPs may protect against allergic disease through several immunological and physiological mechanisms during early-life, including regulation of Th1/Th2 balance, SCFA-induced activation of GPR41/43 and HDAC inhibition, and maturation of epithelial barrier integrity. Taken together, current findings indicate powerful immunomodulatory properties of LBPs on allergic immune response, with LBPs offering exciting potential as a novel therapeutic tool for childhood allergy. However, the efficacy of LBPs in allergy is complex and influenced by many population and methodological factors, resulting in varied therapeutic benefits. While research thus far has focused on traditional probiotic strains, greater investigation into microbial consortiums selected from the microbiota of non-allergic infants may provide greater promise as a therapeutic tool for allergic disease. Further investigation, particularly into long-term efficacy, strain-specific effects, optimal supplementation regimes, and use of multi-strain consortiums, is necessary before findings can be translated into clinical applications to tackle childhood allergic disease. [ABSTRACT FROM AUTHOR]

Summary Oral tolerance promotes the suppression of immune responses to innocuous antigen and is primarily mediated by regulatory T cell (Tregs). The development of oral tolerance begins in early life during a “window of tolerance,” which occurs around weaning and is mediated by components in breastmilk. Herein, we review the factors dictating this window and how Tregs are uniquely educated in early life. In early life, the translocation of luminal antigen for Treg induction is primarily dictated by goblet cell‐associated antigen passages (GAPs). GAPs in the colon are negatively regulated by maternally‐derived epidermal growth factor and the microbiota, restricting GAP formation to the “periweaning” period (postnatal day 11–21 in mice, 4–6 months in humans). The induction of solid food also promotes the diversification of the bacteria such that bacterially‐derived metabolites known to promote Tregs—short‐chain fatty acids, tryptophan metabolites, and bile acids—peak during the periweaning phase. Further, breastmilk immunoglobulins—IgA and IgG—regulate both microbial diversity and the interaction of microbes with the epithelium, further controlling which antigens are presented to T cells. Overall, these elements work in conjunction to induce a long‐lived population of Tregs, around weaning, that are crucial for maintaining homeostasis in adults. [ABSTRACT FROM AUTHOR]

• High-fat diet during early life reshapes the gut microbiome later in life. • Early-life gut dysbiosis associates with disrupted mammary microenvironment later. • Shift of gut microbiome during early life may influence breast health later on. The influence of gut microbiota on gut health is well-documented, but it remains obscure for extraintestinal diseases such as breast cancer. Moreover, it is entirely unknown how gut dysbiosis during early life contributes to breast tumorigenesis later in life. In this study, we hypothesized that a high-fat diet during early life leads to alterations in the gut microbiome and is associated with disruptions in the mammary microenvironment. Female C57BL/6 mice were fed a low-fat diet (10% kcal fat) or a high-fat diet (HF, 60% kcal fat) for 8 weeks from the age of 4 to 12 weeks, which is equivalent to human childhood and adolescence. Twelve mice were sacrificed immediately after the 8-week feeding, the remainder were euthanized after switching to a normal lifecycle-supporting diet for an additional 12 weeks; the gut microbiome was then sequenced. The 8-week HF diet feeding altered the beta-diversity (Bray & Jaccard P <.01), and the difference remained significant after switching the diet (Bray & Jaccard P <.05). Immediately after HF feeding, a greater number of microbial taxa (>50) were altered, and about half of the taxa (25) remained significantly changed after switching the diet. The abundance of Alistipes, Bilophila , and Rikenellaceae stood out as significantly associated with multiple metabolic and inflammatory biomarkers in mammary tissue, including aromatase, Ccl2 , and Cox2. In conclusion, an 8-week early-life HF feeding reshaped the gut microbiome, which connected with disrupted mammary microenvironments. A high-fat diet during early life (4–12 weeks of age in mice), corresponding to childhood and adolescence in humans, significantly influences the gut microbiome and consequently affects the mammary microenvironment, which may ultimately lead to increase the risk of young-onset breast cancer later in life (24 weeks of age in mice), equivalent to the young to middle ages of adulthood in humans. [Display omitted] [ABSTRACT FROM AUTHOR]

• Microglia genetic capacity associates with white matter developmental trajectories. • Microglia genetic capacity is a factor of differential susceptibility. • White matter trajectories mediated microglia associations with social problems. • Findings show sex specificity; only observed in females. There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score (ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes. A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors. Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females. We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems. In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA. Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposures through influences on neurodevelopment. [ABSTRACT FROM AUTHOR]

The correct initial colonization and establishment of the gut microbiota during the early stages of life is a key step, with long-lasting consequences throughout the entire lifespan of the individual. This process is affected by several perinatal factors; among them, feeding mode is known to have a critical role. Breastfeeding is the optimal nutrition for neonates; however, it is not always possible, especially in cases of prematurity or early pathology. In such cases, most commonly babies are fed with infant formulas in spite of the official nutritional and health international organizations' recommendation on the use of donated human milk through milk banks for these cases. However, donated human milk still does not totally match maternal milk in terms of infant growth and gut microbiota development. The present review summarizes the practices of milk banks and hospitals regarding donated human milk, its safety and quality, and the health outcomes in infants fed with donated human milk. Additionally, we explore different alternatives to customize pasteurized donated human milk with the aim of finding the perfect match between each baby and banked milk for promoting the establishment of a beneficial gut microbiota from the early stages of life. [ABSTRACT FROM AUTHOR]

Aim: Eating disorders have a serious impact on quality of life, especially when combined with Type 1 diabetes. We investigated eating disorders in relation to factors early in life with some focus on Type 1 diabetes. Methods: Out of 21,700 children born 1st of Oct 1997–1st of Oct 1999 17,055 (78.6%) were included in ABIS (All Babies in southeast Sweden) and 16,415 had adequate questionnaires. ICD-10 diagnosis from The National Patient Register was merged with the ABIS data. Results: In total 247 individuals, 19 boys (7.7%) and 219 girls (92.3%) out of 16,415 (1.5%) developed eating disorders (EDs), 167 (1.0%) Type 1 diabetes of whom 7 (4.2%) also got eating disorders (ED) (OR 3.25 (1.47–7.28); p = 0.04), all of them years after diagnosis of Type 1 diabetes. EDs was associated with high parental education especially in fathers (OR 1.65 (1.09–2.50); p = 0.02) and to at birth anxiety, and depression among mothers. There was no association with the duration of breastfeeding. Conclusions: Eating disorders are common in girls, with increased risk in high-educated but psychologically vulnerable families. Prevalence is increased in type 1 diabetes. Even modern diabetes treatment needs to be completed with psychological support. Level of evidence: Level III: Evidence obtained from well-designed cohort or case–control analytic studies. [ABSTRACT FROM AUTHOR]

The spread of marine non-indigenous species (NIS) is driven largely by shipping and global trade. Biofouling on vessel hulls is a major source of invasions, but many biofouling organisms are sessile (non-motile) and require reproduction, which often produces mobile, waterborne propagules (e.g., larvae) that can colonize new regions. The ability of biofouling organisms to reproduce, however, can depend strongly on abiotic conditions at the time of reproduction but also potentially prior to any reproductive event. For many organisms, past environments can influence performance later in life via within-generation carryover effects, but how carryover effects influence potential NIS introductions is unclear. We conducted a laboratory experiment to explore within-generation carryover effects of salinity and how they operate across different environments in the barnacle Amphibalanus improvisus, a common biofouling organism. We exposed newly settled barnacles to two different salinities (15 and 28 psu) for three weeks, maintained them in a common salinity for five weeks, then re-exposed them to the two initial salinities in a fully-factorial design prior to measuring their reproductive output. We found that barnacles that switched salinities between the initial and final exposures tended to produce more nauplii larvae (up to 50%) than those that remained in the same salinity conditions, possibly because of a stress response induced by physiological acclimation to early life environments. Because adult biofouling species are likely to be exposed to variable environmental conditions during vessel transits, carryover effects and their impact on propagule output may be important to consider when evaluating potential NIS introductions via biofouling. [ABSTRACT FROM AUTHOR]

Abstract Pregnancy represents a period of immense maternal physiological adaptation, with progressive increases in lipid storage potential and insulin resistance to support fetal/placental growth. This requires significant change in the adipose tissue. Women living with obesity/overweight are more susceptible to these changes causing complications such as gestational diabetes. This is particularly worrying as up to 60% of European women are living with overweight/obesity at the onset of pregnancy. Furthermore, less than 1% meet all nutrition guidelines. There is now evidence that these deep metabolic changes can result in a predisposition to metabolic disease in both the mother and child in later life. Health and nutrition status during this period therefore represents a window to future health. This period offers a valuable opportunity for intervention to prevent the negative consequences of poor in utero environments and increases the long‐term quality of life for mother and offspring. This review will examine a range of in utero factors which determine adipose tissue development, the impact of these factors on later‐life obesity and metabolic health and the therapeutic value of dietary anti‐inflammatory nutritional interventions during pregnancy and early life. When it comes to early life nutrition, a ‘one size fits all’ approach is not always appropriate. Understanding the mechanisms of adipose tissue development in response to differing nutritional strategies may be important in the context of complicated or adverse in utero environments and represents a substantial step towards a more personalised nutritional approach for the prevention of obesity, metabolic syndrome and related non‐communicable diseases in future generations.

Abstract Background The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. Methods The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher’s exact test and logistic regression. Results In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn’s disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70–17.3). Breastfeeding (OR = 0.18, 95% CI 0.08–0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21–0.89) were negatively associated with CD. Conclusions Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

Introduction: Early life growth restriction significantly increases the risk of adulthood physical inactivity and thereby chronic disease incidence. Improvements in motor skill acquisition could result in greater physical activity engagement in the growth-restricted population, thus reducing chronic disease risk. The purpose of this study was to implement an early life motor training intervention to improve physical activity engagement in control and growth-restricted mice. Methods: Mice were growth restricted in early life utilizing a validated nutritive model or remained fully nourished in early life as a control. All mice were tested throughout early life for various components of motor skill acquisition. On postnatal day 10,mice were randomly assigned to engage in an early life motor skill intervention daily until postnatal day 21 or remained as a sedentary control. All mice were given access to an in-cage running wheel from postnatal days 45-70. Results: Growth-restricted group (PGR) mice had impaired trunk and postural control, coordination/vestibular development, and hindlimb strength in early life compared with control mice. There were no differences in wheel running behavior between the trained and sedentary mice, although control mice ran at a faster average speed compared with PGR mice. Control female mice ran more than PGR female mice during the week 2 dark cycle. Conclusions: Early life growth restriction reduced motor skill attainment throughout early life, which may be associated with reduced ability to engage in physical activity in adulthood. The early life motor skill intervention did not elicit changes in body weight or physical activity engagement in control or PGR mice, indicating that a more intense/different intervention specifically targeting skeletal muscle may be necessary to counteract the detrimental effects of early life growth restriction. [ABSTRACT FROM AUTHOR]

Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines. [ABSTRACT FROM AUTHOR]

There is rapidly growing awareness of microbiome assembly and function in early-life gut health. Although many factors, such as antibiotic use and highly processed diets, impinge on this process, most research has focused on people residing in high-income countries. However, much of the world's population lives in low- and middle-income countries (LMICs), where, in addition to erratic antibiotic use and suboptimal diets, these groups experience unique challenges. Indeed, many children in LMICs are infected with intestinal helminths. Although helminth infections are strongly associated with diverse developmental co-morbidities and induce profound microbiome changes, few studies have directly examined whether intersecting pathways between these components of the holobiont shape health outcomes in early life. Here, we summarize microbial colonization within the first years of human life, how helminth-mediated changes to the gut microbiome may affect postnatal growth, and why more research on this relationship may improve health across the lifespan. Intestinal helminth infection and delayed gut microbiome maturation have known individual developmental and long-term adverse health outcomes. Yet, their combined effects in early life remain poorly described. Here, Bogza et al. detail these complex interactions and suggest experimental models to explore their emergent properties on immune, microbial, and infant development. [ABSTRACT FROM AUTHOR]

Summary: Besides its canonical role in protecting the host from pathogens, the immune system plays an arguably equally important role in maintaining tissue homeostasis. Within barrier tissues that interface with the external microenvironment, induction of immune tolerance to innocuous antigens, such as commensal, dietary, and environmental antigens, is key to establishing immune homeostasis. The early postnatal period represents a critical window of opportunity in which parallel development of the tissue, immune cells, and microbiota allows for reciprocal regulation that shapes the long‐term immunological tone of the tissue and subsequent risk of immune‐mediated diseases. During early infancy, the immune system appears to sacrifice pro‐inflammatory functions, prioritizing the establishment of tissue tolerance. In this review, we discuss mechanisms underlying early life windows for intestinal tolerance with a focus on newly identified RORγt+ antigen‐presenting cells–Thetis cells–and highlight the role of the intestinal microenvironment in shaping intestinal immune system development and tolerance. [ABSTRACT FROM AUTHOR]

• Early life Western diet (WD) disrupts memory despite healthy diet intervention. • Early life WD yields long-lasting reductions in hippocampus cholinergic tone. • Early life WD disrupts novelty-induced hippocampal acetylcholine release. • Gut microbiome changes due to early life Western diet are reversible. • Impaired acetylcholine signaling underlies WD-induced memory deficits. Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26–56). Behavioral and metabolic assessments were performed both before and after a healthy diet intervention period beginning at early adulthood. Results revealed HPC-dependent contextual episodic memory impairments in CAF rats that persisted despite the healthy diet intervention. Given that dysregulated HPC acetylcholine (ACh) signaling is associated with memory impairments in humans and animal models, we examined protein markers of ACh tone in the dorsal HPC (HPCd) in CAF and CTL rats. Results revealed significantly lower protein levels of vesicular ACh transporter in the HPCd of CAF vs. CTL rats, indicating chronically reduced ACh tone. Using intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeting the HPCd, we next revealed that ACh release during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Neuropharmacological results showed that alpha 7 nicotinic ACh receptor agonist infusion in the HPCd during training rescued memory deficits in CAF rats. Overall, these findings reveal a functional connection linking early life WD intake with long-lasting dysregulation of HPC ACh signaling, thereby identifying an underlying mechanism for WD-associated memory impairments. [ABSTRACT FROM AUTHOR]

While stromatolites, and to a lesser extent thrombolites, have been extensively studied in order to unravel Precambrian (>539 Ma) biological evolution, studies of clastic‐dominated microbially induced sedimentary structures (MISS) are relatively scarce. The lack of a consolidated record of clastic microbialites creates questions about how much (and what) information on depositional and taphonomic settings can be gleaned from these fossils. We used μCT scanning, a non‐destructive X‐ray‐based 3D imaging method, to reconstruct morphologies of ancient MISS and mat textures in two previously described coastal Archaean samples from the ~3.48 Ga Dresser Formation, Pilbara, Western Australia. The aim of this study was to test the ability of μCT scanning to visualize and make 3D measurements that can be used to interpret the biotic–environmental interactions. Fossil MISS including mat laminae with carpet‐like textures in one sample and mat rip‐up chips in the second sample were investigated. Compiled δ13C and δ34S analyses of specimens from the Dresser Fm. are consistent with a taxonomically diverse community that could be capable of forming such MISS. 3D measurements of fossil microbial mat chips indicate significant biostabilization and suggest formation in flow velocities >25 cm s−1. Given the stratigraphic location of these chips in a low‐flow lagoonal layer, we conclude that these chips formed due to tidal influence, as these assumed velocities are consistent with recent modeling of Archaean tides. The success of μCT scanning in documenting these microbialite features validates this technique both as a first step analysis for rare samples prior to the use of more destructive techniques and as a valuable tool for gaining insight into microbialite taphonomy. [ABSTRACT FROM AUTHOR]

Pregnancy represents a period of immense maternal physiological adaptation, with progressive increases in lipid storage potential and insulin resistance to support fetal/placental growth. This requires significant change in the adipose tissue. Women living with obesity/overweight are more susceptible to these changes causing complications such as gestational diabetes. This is particularly worrying as up to 60% of European women are living with overweight/obesity at the onset of pregnancy. Furthermore, less than 1% meet all nutrition guidelines. There is now evidence that these deep metabolic changes can result in a predisposition to metabolic disease in both the mother and child in later life. Health and nutrition status during this period therefore represents a window to future health. This period offers a valuable opportunity for intervention to prevent the negative consequences of poor in utero environments and increases the long‐term quality of life for mother and offspring. This review will examine a range of in utero factors which determine adipose tissue development, the impact of these factors on later‐life obesity and metabolic health and the therapeutic value of dietary anti‐inflammatory nutritional interventions during pregnancy and early life. When it comes to early life nutrition, a 'one size fits all' approach is not always appropriate. Understanding the mechanisms of adipose tissue development in response to differing nutritional strategies may be important in the context of complicated or adverse in utero environments and represents a substantial step towards a more personalised nutritional approach for the prevention of obesity, metabolic syndrome and related non‐communicable diseases in future generations. What is the topic of this review?The influence of adversein utero environments (obesogenic, undernutrition, gestational diabetes) onadipocyte capacity and the associated risk of obesity and metabolicdysregulation in later life.What advances does it highlight?Novel anti‐inflammatory dietary intervention strategies duringpregnancy that aim prevent obesity and metabolic dysfunction in the offspring. Despiteoverwhelming evidence of inflammatory involvement in obesity and associatedcomorbidities, the involvement of metabolic inflammation on pregnancy andearly‐life programming of metabolic disease has not been investigatedcomprehensively. Studies identifying novel intervention strategies to combat apoor start to life are pivotal in the developmental programming field given thedual approach of both identifying valid nutritional interventions while at thesame time aiding in the identification of molecular targets that influenceadipose tissue function early in the lifecourse. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. Methods: The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher's exact test and logistic regression. Results: In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn's disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70–17.3). Breastfeeding (OR = 0.18, 95% CI 0.08–0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21–0.89) were negatively associated with CD. Conclusions: Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life. [ABSTRACT FROM AUTHOR]

Importance Poly- and perfluoroalkyl substances (PFASs) are nondegradable, man-made chemicals. They accumulate in humans with potential harmful effects, especially in susceptible periods of human development, such as the first months of life. We found that, in our cohort, exclusively breastfed (EBF) infants had 3 times higher PFAS plasma levels compared with exclusively formula-fed (EFF) infants at the age of 3 months. Thus, PFASs could potentially reduce the health benefits of breastfeeding. Objective We investigated the associations between PFAS levels at the age of 3 months and accelerated gain in fat mass during the first 6 months of life, body composition at 2 years, and whether these associations differ between EBF and EFF infants. Setting In 372 healthy term-born infants, we longitudinally assessed anthropometrics, body composition (by air-displacement plethysmography and dual-energy X-ray absorptiometry), and visceral and subcutaneous fat (by abdominal ultrasound) until the age of 2 years. Measures The plasma levels of 5 individual PFASs were determined by liquid chromatography–electrospray ionization–tandem mass spectrometry at the age of 3 months. Main outcomes We studied associations between PFAS levels and outcomes using multiple regression analyses. Results Higher early life plasma perfluorooctanoic acid and total PFAS levels were associated with an accelerated gain in fat mass percentage [FM%; >0.67 SD score (SDS)] during the first 6 months of life. Higher early life PFAS levels were associated with lower fat-free mass (FFM) SDS at the age of 2 years, but not with total FM% SDS at 2 years. Furthermore, we found opposite effects of PFAS levels (negative) and exclusive breastfeeding (positive) at the age of 3 months on FFM SDS at 2 years. Conclusion Higher PFAS levels in early life are associated with accelerated gains in FM% during the first 6 months of life and with lower FFM SDS at the age of 2 years, which have been associated with an unfavorable body composition and metabolic profile later in life. Our findings warrant further research with longer follow-up times. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the long-term effects of the Vietnam War on physical and mental health outcomes of Vietnamese who were children (age 6 to 9 and 10 to 14), teenagers (age 15 to 19), and young adults (age 20 +) during the war, including differences by gender and military participation, and examine the ways in which these effects are moderated by age. Research has documented that the effects of war on physical and mental health may linger well into late adulthood, suggesting a scarring effect of war among wartime children in particular. However, the degree to which scarring differentially affects younger versus older children, or children versus teenagers and young adults, is not well established. Using detailed individual level health data provided by the Vietnam Health and Aging Study (VHAS), we examine the association between the age of exposure to warfare and long-term physical and mental health outcomes of affected cohorts. Our analysis shows that early childhood exposure has long-lasting detrimental effects on an array of adult health outcomes. Wartime children who were exposed before their teen years are significantly more susceptible to functional and physical limitations, and impaired ability to perform daily activities, as older adults. Our results also indicate that while war exposure associates positively with PTSD across all age cohorts, it is pre-teens that are statistically most likely to suffer in old age compared to their older counterparts, suggesting both physical and mental health could be scarred by early childhood exposure to war. Additionally, we find that male wartime children are more likely to suffer from physical limitations, while female wartime children appear to experience PTSD symptoms over the course of their lives. Moreover, children who remained civilian over the course of war disproportionally suffered adverse long-term health effects of war. Taking these findings together, they indicate the importance of post-conflict policy that prioritizes mitigating efforts aimed at improving both physical and mental health of children, particularly those at risk. These targeted post-war policies are critical for not only the post-war recovery, but also for peacekeeping operations within conflict-torn countries. [ABSTRACT FROM AUTHOR]

Children around the world are continuing to develop and suffer from chronic lung diseases such as asthma. Childhood asthma commonly presents with recurrent episodes of cough, shortness of breath, and wheezing, all of which can lead to missed school days and hospitalization admissions. The role of environmental pollutants and aeroallergens has been increasingly recognized in relation to asthma etiology. We showcase the impacts of air pollution and pollen exposures in early life on childhood asthma and allergies through an epidemiologic perspective. We also examine the effects of indoor microbial exposures such as endotoxin and glucan on allergic diseases in schoolchildren as many spend most of their time in a household or classroom setting. Findings of this work can assist in the identification of key environmental factors in critical life periods and improve clinicians’ diagnoses of asthma during early childhood.

The early microbial colonization of human mucosal surfaces is essential for the development of the host immune system. Already during pregnancy, the unborn child is prepared for the postnatal influx of commensals and pathogens via maternal antibodies, and after birth this protection is continued with antibodies in breast milk. During this critical window of time, which extends from pregnancy to the first year of life, each encounter with a microorganism can influence children's immune response and can have a lifelong impact on their life. For example, there are numerous links between the development of allergies and an altered gut microbiome. However, the exact mechanisms behind microbial influences, also extending to how viruses influence host-microbe interactions, are incompletely understood. In this review, we address the impact of infants’ first microbial encounters, how the immune system develops to interact with gut microbiota, and summarize how an altered immune response could be implied in allergies.

With the global prevalence of allergic disease continuing to rise at an alarming rate, the need for effective and safe therapeutics is paramount. Given the critical role of the early-life microbiota on immune development, emerging research suggests the potential use of live biotherapeutic products (LBP) for the prevention and treatment of childhood allergy. However, findings are limited and inconsistent. Therefore, the present review critically evaluates the current animal and human data on the therapeutic value of LBPs in allergy, the underlying immunological mechanisms by which LBPs may mediate allergy susceptibility, limitations of the current research that need to be addressed, and future research directions. Accordingly, LBPs may protect against allergic disease through several immunological and physiological mechanisms during early-life, including regulation of Th1/Th2 balance, SCFA-induced activation of GPR41/43 and HDAC inhibition, and maturation of epithelial barrier integrity. Taken together, current findings indicate powerful immunomodulatory properties of LBPs on allergic immune response, with LBPs offering exciting potential as a novel therapeutic tool for childhood allergy. However, the efficacy of LBPs in allergy is complex and influenced by many population and methodological factors, resulting in varied therapeutic benefits. While research thus far has focused on traditional probiotic strains, greater investigation into microbial consortiums selected from the microbiota of non-allergic infants may provide greater promise as a therapeutic tool for allergic disease. Further investigation, particularly into long-term efficacy, strain-specific effects, optimal supplementation regimes, and use of multi-strain consortiums, is necessary before findings can be translated into clinical applications to tackle childhood allergic disease.

Abstract Human milk oligosaccharides (HMOs) impact neonate immunity and health outcomes. However, the environmental factors influencing HMO composition remain understudied. This study examined the associations between ambient air pollutant (AAP) exposure and HMOs at 1-month postpartum. Human milk samples were collected at 1-month postpartum (n = 185). AAP (PM2.5, PM10, NO2) exposure included the 9-month pregnancy period through 1-month postpartum. Associations between AAP with (1) HMO diversity, (2) the sum of sialylated and fucosylated HMOs, (3) 6 a priori HMOs linked with infant health, and (4) all HMOs were examined using multivariable linear regression and principal component analysis (PCA). Exposure to AAP was associated with lower HMO diversity. PM2.5 and PM10 exposure was positively associated with the HMO 3-fucosyllactose (3FL); PM2.5 exposure was positively associated with the sum of total HMOs, sum of fucosylated HMOs, and the HMO 2′-fucosyllactose (2′FL). PCA indicated the PM2.5, PM10, and NO2 exposures were associated with HMO profiles. Individual models indicated that AAP exposure was associated with five additional HMOs (LNFP I, LNFP II, DFLNT, LNH). This is the first study to demonstrate associations between AAP and breast milk HMOs. Future longitudinal studies will help determine the long-term impact of AAP on human milk composition.

Early life is a critical window period that determines the growth and development of children, but this delicate and complex period is highly susceptible to the disturbance of various exogenous chemicals, which in consequence may lead to short-term or long-term adverse health effects in human beings. The massive use of antibiotics has contributed to widespread exposure in early life, along with the potentially adverse effects on child health, and has caused great concern in public health. This review summarized recent epidemiological studies on the population with early-life antibiotic exposure and associated health outcomes such as growth and development, allergies, and psycho-behavioral problems in children, as well as potential biological mechanisms underlying these associations. Current findings suggested that antibiotic exposure early in life, including pregnancy and infancy, is strongly associated with childhood allergic diseases (e.g., atopic dermatitis and asthma), growth and development (e.g., obesity and birth length), and childhood psycho-behavioral problems (e.g., autism and anxiety). It also suggested that antibiotic exposure may affect individual health through gut microbiota, thyroid function, inflammation factors, mitochondrial function, and epigenetic mechanisms. In the future, more large prospective birth cohorts should be established to determine the levels of internal exposure to different types of antibiotics at multiple time points in early life and to explore their associations with child health outcomes, as well as to further validate relevant mechanisms, aiming to provide high-quality scientific evidence for research on child health associated with environmental exposure in early life.

Abstract Background The gut microbiome undergoes primary ecological succession over the course of early life before achieving ecosystem stability around 3 years of age. These maturational patterns have been well-characterized for bacteria, but limited descriptions exist for other microbiota members, such as fungi. Further, our current understanding of the prevalence of different patterns of bacterial and fungal microbiome maturation and how inter-kingdom dynamics influence early-life microbiome establishment is limited. Results We examined individual shifts in bacterial and fungal alpha diversity from 3 to 12 months of age in 100 infants from the CHILD Cohort Study. We identified divergent patterns of gut bacterial or fungal microbiome maturation in over 40% of infants, which were characterized by differences in community composition, inter-kingdom dynamics, and microbe-derived metabolites in urine, suggestive of alterations in the timing of ecosystem transitions. Known microbiome-modifying factors, such as formula feeding and delivery by C-section, were associated with atypical bacterial, but not fungal, microbiome maturation patterns. Instead, fungal microbiome maturation was influenced by prenatal exposure to artificially sweetened beverages and the bacterial microbiome, emphasizing the importance of inter-kingdom dynamics in early-life colonization patterns. Conclusions These findings highlight the ecological and environmental factors underlying atypical patterns of microbiome maturation in infants, and the need to incorporate multi-kingdom and individual-level perspectives in microbiome research to improve our understandings of gut microbiome maturation patterns in early life and how they relate to host health. Video Abstract

Abstract Aim Eating disorders have a serious impact on quality of life, especially when combined with Type 1 diabetes. We investigated eating disorders in relation to factors early in life with some focus on Type 1 diabetes. Methods Out of 21,700 children born 1st of Oct 1997–1st of Oct 1999 17,055 (78.6%) were included in ABIS (All Babies in southeast Sweden) and 16,415 had adequate questionnaires. ICD-10 diagnosis from The National Patient Register was merged with the ABIS data. Results In total 247 individuals, 19 boys (7.7%) and 219 girls (92.3%) out of 16,415 (1.5%) developed eating disorders (EDs), 167 (1.0%) Type 1 diabetes of whom 7 (4.2%) also got eating disorders (ED) (OR 3.25 (1.47–7.28); p = 0.04), all of them years after diagnosis of Type 1 diabetes. EDs was associated with high parental education especially in fathers (OR 1.65 (1.09–2.50); p = 0.02) and to at birth anxiety, and depression among mothers. There was no association with the duration of breastfeeding. Conclusions Eating disorders are common in girls, with increased risk in high-educated but psychologically vulnerable families. Prevalence is increased in type 1 diabetes. Even modern diabetes treatment needs to be completed with psychological support. Level of evidence Level III: Evidence obtained from well-designed cohort or case–control analytic studies.

Autism spectrum disorders (ASD) are highly heritable, heterogeneous neurodevelopmental disorders characterized by clinical presentation of atypical social, communicative, and repetitive behaviors. Over the past 25 years, hundreds of ASD risk genes have been identified. Many converge on key molecular pathways, from translational control to those regulating synaptic structure and function. Despite these advances, therapeutic approaches remain elusive. Emerging data unearthing the relationship between genetics, microbes, and immunity in ASD suggest an integrative physiology approach could be paramount to delivering therapeutic breakthroughs. Indeed, the advent of large-scale multi-OMIC data acquisition, analysis, and interpretation is yielding an increasingly mechanistic understanding of ASD and underlying risk factors, revealing how genetic susceptibility interacts with microbial genetics, metabolism, epigenetic (re)programming, and immunity to influence neurodevelopment and behavioral outcomes. It is now possible to foresee exciting advancements in the treatment of some forms of ASD that could markedly improve quality of life and productivity for autistic individuals. Here, we highlight recent work revealing how gene X maternal exposome interactions influence risk for ASD, with emphasis on the intrauterine environment and fetal neurodevelopment, host–microbe interactions, and the evolving therapeutic landscape for ASD.

ABSTRACTEarly life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.

Ancestral sequence reconstruction (ASR) infers predicted ancestral states for sites within sequences and can constrain the functions and properties of ancestors of extant protein families. Here, we compare the likely sequences of inferred nitrogenase ancestors to extant nitrogenase sequence diversity. We show that the most-likely combinations of ancestral states for key substrate channel residues are not represented in extant sequence space, and rarely found within a more broadly defined physiochemical space-supporting that the earliest ancestors of extant nitrogenases likely had alternative substrate channel composition. These differences may indicate differing environmental selection pressures acting on nitrogenase substrate specificity in ancient environments. These results highlight ASR's potential as an in silico tool for developing hypotheses about ancestral enzyme functions, as well as improving hypothesis testing through more targeted in vitro and in vivo experiments.

Asthma is the most common chronic disease among children, with more than 300 million cases worldwide. Over the past several decades, asthma incidence has grown, and epidemiological studies identify the modernized lifestyle as playing a strong contributing role in this phenomenon. In particular, lifestyle factors that modify the maternal gut microbiome during pregnancy, or the infant microbiome in early life, can act as developmental programming events which determine health or disease susceptibility later in life. Microbial colonization of the gut begins at birth, and factors such as delivery mode, breastfeeding, diet, antibiotic use, and exposure to environmental bacteria influence the development of the infant microbiome. Colonization of the gut microbiome is crucial for proper immune system development and disruptions to this process can predispose a child to asthma development. Here, we describe the importance of early‐life events for shaping immune responses along the gut‐lung axis and why they may provide a window of opportunity for asthma prevention. [ABSTRACT FROM AUTHOR]

Caffeine is a substance with central and metabolic effects. Although it is recommended that its use be limited during pregnancy, many women continue to consume caffeine. Direct and indirect actions of caffeine in fetuses and newborns promote adaptive changes, according to the Developmental Origins of Health and Diseases (DOHaD) concept. In fact, epidemiological and experimental evidence reveals the impact of early caffeine exposure. Here, we reviewed these findings with an emphasis on experimental models with rodents. The similarity of human and rodent caffeine metabolism allows the comprehension of molecular mechanisms affected by prenatal caffeine exposure. Maternal caffeine intake affects the body weight and endocrine system of offspring at birth and has long-term effects on the endocrine system, liver function, glucose and lipid metabolism, the cardiac system, the reproductive system, and behavior. Interestingly, some of these effects are sex dependent. Thus, the dose of caffeine considered safe for pregnant women may not be adequate for the prenatal period. [ABSTRACT FROM AUTHOR]

Over the last decades, mass mortality events have become increasingly common across taxa with sometimes devastating effects on population biomass. In the aquatic environment, fish are sensitive to mass mortality events, particularly at the early life stages that are crucial for population dynamics. However, it has recently been shown for fish, that a single mass mortality event in early life typically does not lead to population collapse. Moreover, the frequency and intensity of extreme events that can cause mass mortality, such as marine heatwaves, are increasing. Here, we show that increasing frequency and intensity of mass mortality events may lead to population collapse. Since the drivers of mass mortality events are diverse, and often linked to climate change, it is challenging to predict the frequency and severity of future mass mortality events. As an alternative, we quantify the probability of population collapse depending on the frequency and intensity as well as the duration of mass mortality events. Based on 39 fish species, we show that the probability of collapse typically increases with increasing frequency, intensity, and duration of the mortality events. In addition, we show that the collapse depends on key traits such as natural mortality, recruitment variation, and density dependence. The presented framework provides quantitative estimates of the sensitivity of fish species to these increasingly common extreme events, which paves the way for potential mitigation actions to alleviate adverse impacts on harvested fish populations across the globe. [ABSTRACT FROM AUTHOR]

Altered intestinal health is also associated with the incidence and severity of many chronic inflammatory conditions, which could be attenuated via dietary n-3 PUFA interventions. However, little is known about the effect of lifelong exposure to n-3 PUFA from plant and marine sources (beginning in utero via the maternal diet) on early life biomarkers of intestinal health. Harems of C57Bl/6 mice were randomly assigned to one of three isocaloric AIN-93G modified diets differing in their fat sources consisting of the following: (i) 10% safflower oil (SO, enriched in n-6 PUFA), (ii) 3% flaxseed oil + 7% safflower oil (FX, plant-based n-3 PUFA-enriched diet), or (iii) 3% menhaden fish oil + 7% safflower oil (MO, marine-based n-3 PUFA-enriched diet). Mothers remained on these diets throughout pregnancy and offspring (n = 14/diet) continued on the same parental diet until termination at 3 weeks of age. In ileum, villi:crypt length ratios were increased in both the FX and MO dietary groups compared to SO (p < 0.05). Ileum mRNA expression of critical intestinal health biomarkers was increased by both n-3 PUFA-enriched diets including Relmβ and REG3γ compared to SO (p < 0.05), whereas only the FX diet increased mRNA expression of TFF3 and Muc2 (p < 0.05) and only the MO diet increased mRNA expression of ZO-1 (p < 0.05). In the proximal colon, both the FX and MO diets increased crypt lengths compared to SO (p < 0.05), whereas only the MO diet increased goblet cell numbers compared to SO (p < 0.05). Further, the MO diet increased proximal colon mRNA expression of Relmβ and REG3γ (p < 0.05) and both MO and FX increased mRNA expression of Muc2 compared to SO (p < 0.05). Collectively, these results demonstrate that lifelong exposure to dietary n-3 PUFA, beginning in utero, from both plant and marine sources, can support intestinal health development in early life. The differential effects between plant and marine sources warrants further investigation for optimizing health. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome undergoes primary ecological succession over the course of early life before achieving ecosystem stability around 3 years of age. These maturational patterns have been well-characterized for bacteria, but limited descriptions exist for other microbiota members, such as fungi. Further, our current understanding of the prevalence of different patterns of bacterial and fungal microbiome maturation and how inter-kingdom dynamics influence early-life microbiome establishment is limited. Results: We examined individual shifts in bacterial and fungal alpha diversity from 3 to 12 months of age in 100 infants from the CHILD Cohort Study. We identified divergent patterns of gut bacterial or fungal microbiome maturation in over 40% of infants, which were characterized by differences in community composition, inter-kingdom dynamics, and microbe-derived metabolites in urine, suggestive of alterations in the timing of ecosystem transitions. Known microbiome-modifying factors, such as formula feeding and delivery by C-section, were associated with atypical bacterial, but not fungal, microbiome maturation patterns. Instead, fungal microbiome maturation was influenced by prenatal exposure to artificially sweetened beverages and the bacterial microbiome, emphasizing the importance of inter-kingdom dynamics in early-life colonization patterns. Conclusions: These findings highlight the ecological and environmental factors underlying atypical patterns of microbiome maturation in infants, and the need to incorporate multi-kingdom and individual-level perspectives in microbiome research to improve our understandings of gut microbiome maturation patterns in early life and how they relate to host health. 5AtmDGbifCkZAT-p1B-BuF Video Abstract [ABSTRACT FROM AUTHOR]

The development of antibiotics was a turning point in the history of medicine; however, their misuse and overuse have contributed to the current global epidemic of antibiotic resistance. According to epidemiological studies, early antibiotic exposure increases the risk of immunological and metabolic disorders. This study investigated the effects of exposure to different doses of sulfamethazine (SMZ) on offspring mice and compared the effects of exposure to SMZ on offspring mice in prenatal and early postnatal periods and continuous periods. Furthermore, the effects of SMZ exposure on the gut microbiota of offspring mice were analyzed using metagenome. According to the results, continuous exposure to high-dose SMZ caused weight gain in mice. IL-6, IL-17A, and IL-10 levels in the female offspring significantly increased after high-dose SMZ exposure. In addition, there was a significant gender difference in the impact of SMZ exposure on the gut microbiota of offspring: Continuous high-dose SMZ exposure significantly decreased the relative abundance of Ligilactobacillus murinus, Limosilactobacillus reuteri, Lactobacillus johnsonii, and Bifidobacterium pseudolongum (p < 0.05) in female offspring mice; however, these significant changes were not observed in male offspring mice. [ABSTRACT FROM AUTHOR]

Here we investigate possible carryover effects of experimentally increased incubation temperatures for postnatal growth, metabolism, and parental care within and among 6 north temperate and one tropical songbird species. Increased temperatures during embryonic development consistently caused higher postnatal resting metabolism compared to control nests, among but not within the 7 species studied. The effects of the experiment on growth were species specific and depended on the morphometric considered. Size before the fledge date was positively correlated with feeding rate, and metabolism was lower in larger broods. Our experiment did not elicit changes in parental food delivery rates or brooding effort during the postnatal stage, and higher brooding effort was associated with nestlings of smaller mass and faster metabolism independently from treatment. Consequently, parental care seemed unlikely to be the cause of the differences in growth rates between treatments. Instead, physiological mechanisms triggered by our heating treatment appear to be responsible for the observed variation in growth. These intrinsic changes unmatched by adjustments in parental effort may contribute to longer-term consequences for individual quality and survival that deserve further attention. [ABSTRACT FROM AUTHOR]

Multiple studies have shown that clinical events resulting into neonatal IL-4 over-exposure, such as asthma in early life and food allergy, were associated with brain damage and that the neuroinflammation induced by them might lead to cognitive impairments, anxiety-/depressive-like behaviors. IL-4 is the most major elevated cytokine in periphery when these clinical events occur and peripheral IL-4 level positively correlates with the severity of those events. Our previous studies have verified that neonatal IL-4 over-exposure induced a delayed neuroinflammatory damage in rodents, which might have adverse implications for brain development and cognition. Neuroinflammation in brain parenchyma is often accompanied by changes in CSF cytokines levels. However, whether the cytokines levels in CSF change after neonatal IL-4 over-exposure is unknown. Here, we found a delayed pro-inflammatory cytokines response (higher IL-6, IL-1β and, TNF levels) in both hippocampus and CSF after an instant anti-inflammatory cytokine response in IL-4 over-exposed rats. Moreover, the pro-inflammatory cytokines response appeared earlier in CSF than in hippocampus. The level of each of the pro-inflammatory cytokines in CSF positively correlated with that in hippocampus at the age of postnatal day 42. More microglia numbers/activation and higher M-CSF level in the hippocampus in IL-4 over-exposed rats were also observed. Furthermore, there were more macrophages with inflammatory activation in dural mater of IL-4 over-exposed rats. In sum, neonatal IL-4 over-exposure in rats induces delayed inflammation in CSF, suggesting CSF examination may serve as a potential method in predicting delayed neuroinflammation in brain following neonatal IL-4 over-exposure. [ABSTRACT FROM AUTHOR]

Mental health is a priority area for global health, with a particular focus on well-being in majority of the world countries. Attention to early life demonstrates the significance of infant well-being for long-term health. International organisations such as the United Nations International Children’s Emergency Fund (UNICEF), World Health Organization (WHO), and the World Bank guidelines shape interventions in the majority world. At the same time, there are severe shortages of trained mental health personnel on the African continent and growing concerns about the potentially skewed evidence base that informs the science of interventions. Scholars across a range of disciplines are calling for attention to more diverse evidence sources; for better understandings of the syndemic interactions that shape mental health and for interventions that take account of local ideals while retaining a strong evidence base. As questions of how best to secure infant well-being and the adequacy of knowledge surrounding it emerges with growing force on the global scene, it is critical that the full range of infants’ worlds are represented in scholarship. What do exposures to structural violence, interpersonal violence, social assault, and environmental insult mean for our understanding of ‘normal’ development both in our context and globally? What are the dangers of not accounting for these exposures? What evidence bases matter? How do we know? These are critical questions. They arise in the context of limited, under-resourced and often poorly supported opportunities for adequate screening, early recognition, and suitable interventions for both infants and caregivers in Africa.

The blood levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been thoroughly investigated in Greek children from the Rhea birth cohort study. This investigation aimed to assess exposure levels, explore their possible relationship with children's age and sex, and indicate potential sources of exposure. Exposure patterns and common sources of PCBs and OCPs were analyzed using bivariate and multivariate statistics.A total of 947 blood samples from study participants were analyzed for OCP and PCB exposure, with 375 samples collected at 4 years old, 239 at 6.5 years old, and 333 at 11 years old. Elevated levels of DDE were observed in 6.5-year-old children compared to corresponding levels in other European countries. Higher levels of DDE were found in 4-year-old children, with the lowest concentrations in the 11-year-old group. The DDT/DDE ratio was consistently less than 1 among all the examined subjects. These results indicate exposure to DDT and DDE both in utero and through breastfeeding and dietary intake. For the entire cohort population, the highest concentration was determined for PCB 28, followed by PCBs 138, 153, and 180. The sum of the six indicator PCBs implied low exposure levels for the majority of the cohort population. Spearman correlations revealed strong associations between PCBs and OCPs, while principal component analysis identified two different groupings of exposure. DDE exhibited a correlation with a series of PCBs (153, 156, 163, 180), indicating a combined OCP-PCB source, and an anticorrelation with others (52, 28, 101), implying a separate and competing source.

Recent research has hypothesized that hydrogen peroxide (H2O2) may have emerged from abiotic geochemical processes during the Archean eon (4.0–2.5 Ga), stimulating the evolution of an enzymatic antioxidant system in early life. This eventually led to the evolution of cyanobacteria, and in turn, the accumulation of oxygen on Earth. In the latest issue of Redox Biology, Koppenol and Sies (vol. 29, no. 103012, 2024) argued against this hypothesis and suggested instead that early organisms would not have been exposed to H2O2 due to its short half-life in the ferruginous oceans of the Archean. We find these arguments to be factually incomplete because they do not consider that freshwater or some coastal marine environments during the Archean could indeed have led to H2O2 generation and accumulation. In these environments, abiotic oxidants could have interacted with early life, thus steering its evolutionary course.

Abstract Background Beef cattle experience several management challenges across their lifecycle. Castration and weaning, two major interventions in the early life of beef cattle, can have a substantial impact on animal performance. Despite the key role of the rumen microbiome on productive traits of beef cattle, the effect of castration timing and weaning strategy on this microbial community has not been formally described. We assessed the effect of four castration time windows (at birth, turnout, pre-weaning and weaning) and two weaning strategies (fence-line and truck transportation) on the rumen microbiome in a randomized controlled study with 32 male calves across 3 collection days (i.e., time points). Ruminal fluid samples were submitted to shotgun metagenomic sequencing and changes in the taxonomic (microbiota) and functional profile (metagenome) of the rumen microbiome were described. Results Using a comprehensive yet stringent taxonomic classification approach, we identified 10,238 unique taxa classified under 40 bacterial and 7 archaeal phyla across all samples. Castration timing had a limited long-term impact on the rumen microbiota and was not associated with changes in alpha and beta diversity. The interaction of collection day and weaning strategy was associated with changes in the rumen microbiota, which experienced a significant decrease in alpha diversity and shifts in beta diversity within 48 h post-weaning, especially in calves abruptly weaned by truck transportation. Calves weaned using a fence-line weaning strategy had lower relative abundance of Bacteroides, Lachnospira, Fibrobacter and Ruminococcus genera compared to calves weaned by truck transportation. Some genes involved in the hydrogenotrophic methanogenesis pathway (fwdB and fwdF) had higher relative abundance in fence-line-weaned calves post-weaning. The antimicrobial resistance gene tetW consistently represented more than 50% of the resistome across time, weaning and castration groups, without significant changes in relative abundance. Conclusions Within the context of this study, castration timing had limited long-term effects on the rumen microbiota, while weaning strategy had short-term effects on the rumen microbiota and methane-associated metagenome, but not on the rumen resistome.

Abstract Background Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter

Abstract Background Four-chambered stomach including the forestomachs (rumen, reticulum, and omasum) and abomasum allows ruminants convert plant fiber into high-quality animal products. The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants, especially the immune development. However, the dynamics of immune development are poorly understood. Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep, at 5, 10, 15, and 25 days of age. We found that forestomachs share similar gene expression patterns, all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25, whereas the metabolic function were significantly downregulated with age. We constructed a cell landscape of the four-chambered stomach using single-cell sequencing. Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells, monocytes and macrophages, as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues. Moreover, the non-immune cells such as epithelial cells play key roles in immune maturation. Cell communication analysis predicted that in addition to immune cells, non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs. Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life. We also identified the gene expression patterns and functional cells associated with immune development. Additionally, we identified some key receptors and signaling involved in immune regulation. These results help to understand the early life immune development at single-cell resolution, which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

Background: Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) from a mine fire, background PM2.5, and allergic sensitisation later in childhood. Methods: We measured specific immunoglobulin E (IgE) levels for seven common aeroallergens as well as total IgE levels in a cohort of children who had been exposed to the Hazelwood coal mine fire, either in utero or during their first two years of life, in a regional area of Australia where ambient levels of PM2.5 are generally low. We estimated personal exposure to fire-specific emissions of PM2.5 based on a high-resolution meteorological and pollutant dispersion model and detailed reported movements of pregnant mothers and young children during the fire. We also estimated the usual background exposure to PM2.5 at the residential address at birth using a national satellite-based land-use regression model. Associations between both sources of PM2.5 and sensitisation to dust, cat, fungi, and grass seven years after the fire were estimated with logistic regression, while associations with total IgE levels were estimated with linear regression. Results: No association was found between the levels of exposure at either developmental stage to fire-related PM2.5 and allergic sensitisation seven years after the event. However, levels of background exposure were positively associated with sensitisation to dust (OR = 1.90, 95%CI = 1.12,3.21 per 1 μg/m3). Conclusions: Chronic but low exposure to PM2.5 in early life could be more strongly associated with allergic sensitisation in childhood than time-limited high exposure levels, such as the ones experienced during landscape fires. [ABSTRACT FROM AUTHOR]

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period early in life, there is growing evidence that the establishment of healthy gut microbiota plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of the gut microbiota colonisation depends on several dietary factors, including breastfeeding. In this respect, a relationship between breastfeeding and the risk of inflammatory bowel disease (IBD) has been suggested. IBDs are chronic intestinal diseases, and perinatal factors may be partly responsible for their onset. We review the existence of links between breastfeeding and IBD based on experimental and clinical studies. Overall, despite encouraging experimental data in rodents, the association between breastfeeding and the development of IBD remains controversial in humans, partly due to the considerable heterogeneity between clinical studies. The duration of exclusive breastfeeding is probably decisive for its lasting effect on IBD. Thus, specific improvements in our knowledge could support dietary interventions targeting the gut microbiome, such as the early use of prebiotics, probiotics or postbiotics, in order to prevent the disease. [ABSTRACT FROM AUTHOR]

Objectives Very early-life conditions are recognized as critical for healthy brain development. This study assesses early-life risk factors for developing dementia. In the absence of historical medical birth records, we leverage an alternative full population approach using demographic characteristics obtained from administrative data to derive proxy indicators for birth complications and unfavorable birth outcomes. We use proxy variables to investigate the impact of early-life risk factors on dementia risk. Methods We use administrative individual-level data for full cohorts born 1932–1950 in Sweden with multigenerational linkages. Records on hospitalization and mortality are used to identify dementia cases. We derive 3 birth risk factors based on demographic characteristics: advanced maternal age, narrow sibling spacing, and twin births, and apply survival analysis to evaluate long-term effects on dementia risk. We control for confounding using multiple indicators for socio-economic status (SES), including parental surnames, and by implementing a sibling design. As comparison exposure, we add low education from the 1970 Census. Results The presence of at least 1 birth risk factor increases dementia risk (HR = 1.059; 95% CI: 1.034, 1.085). The occurrence of twin births poses a particularly heightened risk (HR = 1.166; 95% CI: 1.084, 1.255). Discussion Improvements to the very early-life environment hold significant potential to mitigate dementia risk. A comparison to the influence of low education on dementia (the largest known modifiable risk factor) suggests that demographic birth characteristics are of relevant effect sizes. Our findings underscore the relevance of providing assistance for births experiencing complications and adverse health outcomes to reduce dementia cases. [ABSTRACT FROM AUTHOR]