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Abstract Carbon with depleted d13C (down to − 25.6‰ VPDB) found in > 3.7 billion year old metamorphic sediments from the Isua Supracrustal Belt, Southwestern Greenland, has been proposed to represent the oldest remains of life on Earth. Graphitic inclusions within garnet porphyroblasts from this locality have been shown to associate with elements consistent with biogenic remains. In this report, we focus on certain liquid inclusions found in the Isua garnets, characterizing their chemical composition using atomic force microscopy, AFM-based infrared spectroscopy, optical photothermal infrared spectroscopy, Raman spectroscopy, and time-of-flight secondary ion mass spectrometry. Our results show that the liquid inclusions contain functional groups consisting of carbon, nitrogen, and oxygen in a configuration similar to amide functional groups. We suspect that the amide groups formed from N, O and C-containing volatile components that were released from the original kerogenous material enclosed in the garnets, as this was graphitized during thermal maturation. This is consistent with the observed inclusion assemblage of solid graphitic and viscous fluid inclusions alike. Our observations are compatible with the inclusions forming from biogenic precursor material, and when considered alongside previous reports on the carbonaceous material in the Isua metamorphic sediments, these and our study collectively indicate that the carbonaceous material in the Isua metasediments represents the oldest traces of life on Earth.

Bacteria, as the major component of the human microbiome, have been shown to play important physiological roles in human health and disease development. However, a growing body of research suggests that fungi, which make up less than 1% of the human microbiome, also have a significant impact on human health, particularly in early life. Fungal colonization is strongly associated with the onset of future childhood diseases such as infectious diseases, allergic diseases, and intestinal diseases. Factors influencing early life, such as mode of birth and use of antibiotics, may be involved in the development of related diseases by affecting fungal colonization, but more research is needed to summarize this. This article reviews the characteristics of the fungal composition in the first 1 000 days of life, the related factors influencing the colonization of the early life fungal community, and the association between fungal dysbiosis and childhood diseases, providing a reference for the prevention and control of related childhood diseases.

Maintaining immune homeostasis is crucial for neonatal health following birth, as neonates encounter the colonization of gut flora and a plethora of external antigens. Myeloid-derived suppressor cells (MDSCs), a group of innate immune cells of myeloid origin with immunosuppressive functions, are known for their significant role in promoting tumor progression. Recent studies, however, have highlighted the critical immunoprotective functions of neonatal MDSCs. Unlike tumor-associated MDSCs, neonatal MDSCs exhibit strong antibacterial activity and play a vital role in preventing inflammatory responses in newborns. This review provides a comprehensive overview of the etiology, characteristics, immunomodulatory functions, and regulatory mechanisms of neonatal MDSCs, emphasizing their role in neonatal inflammatory diseases. This insight aims to provide new strategies for the immunotherapy of neonatal inflammatory diseases.

Early-life gut microbiota development depends on a highly synchronized microbial colonization process in which diet is a key regulator. Microbiota transition toward a more adult-like state in toddlerhood goes hand in hand with the transition from a milk-based diet to a family diet. Microbiota development during the first year of life has been extensively researched; however, studies during toddlerhood remain sparse. Young children's requirement for micronutrients, such as dietary iron, is higher than adults. However, their intake is usually sub-optimal based on regular dietary consumption. The Child Health and Residence Microbes (CHaRM) study, conducted as an adjunct to the GUMLi (Growing Up Milk “Lite”) trial, was a double-blind randomized controlled trial to investigate the effects on body composition of toddler milk compared to unfortified standard cow's milk in healthy children between 1 and 2 years of age in Brisbane (Australia). In this trial, fortified milk with reduced protein content and added synbiotics [Bifidobacterium breve M-16V, short-chain galactooligosaccharides, and long-chain fructooligosaccharides (ratio 9:1)] and micronutrients were compared to standard unfortified cow's milk. In the present study, the effects of the intervention on the gut microbiota and its relationship with iron status in toddlers were investigated in a subset of 29 children (18 in the Active group and 11 in the Control group) who completed the CHaRM study. The toddler microbiota consisted mainly of members of the phyla Firmicutes, Bacteroidota, and Actinobacteriota. The abundance of the B. breve species was quantified and was found to be lower in the Control group than in the Active group. Analysis of blood iron markers showed an improved iron status in the Active group. We observed a positive correlation between Bifidobacterium abundance and blood iron status. PICRUSt, a predictive functionality algorithm based on 16S ribosomal gene sequencing, was used to correlate potential microbial functions with iron status measurements. This analysis showed that the abundance of predicted genes encoding for enterobactin, a class of siderophores specific to Enterobacteriaceae, is inversely correlated with the relative abundance of members of the genus Bifidobacterium. These findings suggest that healthy children who consume a young child formula fortified with synbiotics as part of a healthy diet have improved iron availability and absorption in the gut and an increased abundance of Bifidobacterium in their gut microbiome.

Background: Pollen exposure is an environmental risk factor for asthma symptoms and allergic reactions in children. The extent to which pollen exposure in pregnancy and the first year of life influences the development of childhood asthma and rhinitis is not fully understood. Objective: We aimed to investigate early life exposures to pollen with childhood asthma and rhinitis at age 6 in a longitudinal birth cohort of the United Kingdom. Methods: In this retrospective cohort study, via logistic regressions, we analyzed the associations between pollen exposures in pregnancy and the first year of life with childhood asthma and rhinitis. Results: Higher pollen exposure accumulated during pregnancy and during the first year of life both associated with an increased odds of asthma at age 6 (OR = 1.14, 95% CI 1.03–1.26, p = 0.01; OR = 1.15, 95% CI 1.03–1.29, p = 0.02, respectively). We did not observe statistically significant associations between early life pollen exposures and the odds of rhinitis at the same age. Conclusion: High pollen exposure during early life (prenatal and postnatal) associated with an increased risk of asthma incidence at age 6. Further studies are desired to validate these findings and to elucidate the mechanisms of early life exposures to pollen on asthma etiology.

IntroductionThe incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease.MethodsIn this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility.ResultsOur findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition.DiscussionOur findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases.

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.

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.

Background and Objective Our knowledge of socioeconomic status (SES) and emergency department (ED) visits in adults with a history of severe childhood asthma is limited. Our aim was, therefore, to investigate these variables in individuals with a history of severe childhood asthma compared to a control population.Methods The Kongsberg cohort comprises Danish individuals with a history of severe childhood asthma and a previous 4-month stay at an asthma care facility in Kongsberg, Norway, between 1950 and 1979. The cohort was compared 1:1 to sex and age matched controls with no previous diagnosis of or treatment for obstructive airway disease (OAD). Data from the national Danish health registries were used for comparing cases and controls.Results A total of 1394 adults from the Kongsberg cohort were alive and residing in Denmark (mean age 63 years, 43% females) at the index date (June 2022). A Charlson comorbidity index score of ≥1 was higher in the study cohort compared to controls (7% versus 3%) (p

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.

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.

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.

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

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 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.

Abstract Background Chronic airway disease in adults may have its origin in early life. The purpose of this study is to investigate the long-term prognosis of severe childhood asthma in search for an association between asthma in early life and obstructive lung disease in adulthood. Methods This study is based on the Kongsberg cohort, which includes approximately 5000 children with severe asthma with a 4-month stay at the asthma care facility in Kongsberg, Norway during the years 1950 to 1979. An on average 60-year observational study based on a follow-up examination will be performed including questionnaires, blood samples, and tests of lung function and bronchial responsiveness. Blood samples will be stored in a biobank. In addition, we will conduct further analyses of the cohort based on nationwide register data, including socio-economic parameters and mortality. Discussion Chronic airway disease is associated with substantial burden for both the individual patient and society. Our knowledge of early life origins of chronic airway disease later in life has been increasing in recent decades but is still limited. By exploring early life risk factors for chronic airway disease in adulthood, we may gain insights paving the way for future reduction in the burden of chronic airway diseases.

Cadmium exposure during pregnancy is a non-negligible public health problem which may increase the risk of shortened telomere length in newborns and cardiovascular metabolic health damage in children, and has attracted attention from many researchers in recent years. This article reviewed recent studies both domestically and internationally on the associations among cadmium exposure during pregnancy, shortened telomere length in newborns, and cardiovascular metabolic abnormalities in children, and briefly outlined possible mechanisms of shortened telomere length in newborns by cadmium exposure during pregnancy. Current research results showed that cadmium exposure during pregnancy is related to shortened telomere length in newborns and cardiovascular metabolic abnormalities in children, and shortened telomere length in newborns is also related to cardiovascular metabolic abnormalities in children. It suggested that telomere length in newborns may be a biomarker reflecting cardiovascular metabolic abnormalities in children caused by cadmium exposure during pregnancy. In addition, the current potential mechanisms of cadmium exposure during pregnancy accelerating neonatal telomere length shortening include inflammatory reaction, mitochondrial dysfunction, antioxidant consumption/antioxidant enzyme inactivation, and DNA methylation, and these biological mechanisms are associated with cardiovascular metabolic abnormalities through certain factors, such as obesity, elevated blood pressure, impaired fasting blood glucose, and dyslipidemia in children, suggesting that cardiovascular metabolic abnormalities in children may be programmed in early life, but there are still few relevant studies. In the future, research should be conducted on the association among cadmium exposure during pregnancy, telomere length, and offspring cardiovascular metabolism, as well as possible mediating efficacy and related biological mechanisms of telomere length, aiming to provide early-life biological information for the prevention of cardiovascular and metabolic diseases.

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 Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD. Results The higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup’s immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups’ microbiota. Conclusions Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice. Video Abstract

Abstract In early life, the intestinal mucosa and immune system undergo a critical developmental process to contain the expanding gut microbiome while promoting tolerance toward commensals, yet the influence of maternal diet and microbial composition on offspring immune maturation remains poorly understood. We colonized germ‐free mice with a consortium of 14 strains, fed them a standard fiber‐rich chow or a fiber‐free diet, and then longitudinally assessed offspring development during the weaning period. Unlike pups born to dams fed the fiber‐rich diet, pups of fiber‐deprived dams demonstrated delayed colonization with Akkermansia muciniphila, a mucin‐foraging bacterium that can also use milk oligosaccharides. The pups of fiber‐deprived dams exhibited an enrichment of colonic transcripts corresponding to defense response pathways and a peak in Il22 expression at weaning. Removal of A. muciniphila from the community, but maintenance on the fiber‐rich diet, was associated with reduced proportions of RORγt‐positive innate and adaptive immune cell subsets. Our results highlight the potent influence of maternal dietary fiber intake and discrete changes in microbial composition on the postnatal microbiome assemblage and early immune development.

The prevalence and severity of allergic diseases have increased over the last 30 years. Understanding the mechanisms responsible for these diseases is a major challenge in current allergology, as it is crucial for the transition towards precision medicine, which encompasses predictive, preventive, and personalized strategies. The urge to identify predictive biomarkers of allergy at early stages of life is crucial, especially in the context of major allergic diseases such as food allergy and atopic dermatitis. Identifying these biomarkers could enhance our understanding of the immature immune responses, improve allergy handling at early ages and pave the way for preventive and therapeutic approaches. This minireview aims to explore the relevance of three biomarker categories (proteome, microbiome, and metabolome) in early life. First, levels of some proteins emerge as potential indicators of mucosal health and metabolic status in certain allergic diseases. Second, bacterial taxonomy provides insight into the composition of the microbiota through high-throughput sequencing methods. Finally, metabolites, representing the end products of bacterial and host metabolic activity, serve as early indicators of changes in microbiota and host metabolism. This information could help to develop an extensive identification of biomarkers in AD and FA and their potential in translational personalized medicine in early life.

Summary: The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health in later life. Early-life pharmaceutical exposure, mainly referring to exposure during pregnancy, childbirth, and infancy, may change the structure and function of gut microbiota and affect later human health. In this Review, we describe how healthy gut microbiota is established in early life. We summarise the commonly prescribed medications during early life, including antibiotics, acid suppressant medications and other medications such as antidepressants, analgesics and steroid hormones, and discuss how these medication-induced changes in gut microbiota are involved in the pathological process of diseases, including infections, inflammatory bowel disease, metabolic diseases, allergic diseases and neurodevelopmental disorders. Finally, we review some critical methods such as dietary therapy, probiotics, prebiotics, faecal microbiota transplantation, genetically engineered phages, and vagus nerve stimulation in early life, aiming to provide a new strategy for the prevention of adverse health outcomes caused by prescribed medications exposure in early life.

BackgroundFew effective health interventions transition from smaller efficacy or effectiveness studies to real-world implementation at scale, representing a gap between evidence and practice. Recognising this, we have developed Nutrition Now – a tailored digital resource building on four efficacious dietary interventions, aiming to improve nutrition in the important first 1,000 days of life. Nutrition Now targets and guides expectant parents and parents of 0–2 year olds, serves as a reliable source of evidence-based information for midwives and public health nurses at maternal and child healthcare (MCH) centres, and offers pedagogical tools for early childhood education and care (ECEC) staff. The aim of this study is to implement Nutrition Now at scale and evaluate the impact of different sets of multifaceted implementation strategies on implementation outcomes.MethodsA quasi-experimental design with three study arms will be used, providing either low, medium or high implementation support, when rolled out in 50 municipalities in 2 counties in Norway. Nutrition Now will be implemented in MCH and ECEC settings and made available to expectant parents and parents of 0–2 year olds through social media and MCH. The implementation support builds on strategies described in the Expert Recommendations for Implementing Change (ERIC) implementation framework and is informed by dialogues with stakeholders. Impact of the different degree of implementation support will be assessed by examining reach, adoption, fidelity, and sustainability using usage data generated from the Nutrition Now resource, publicly available municipal data and qualitative interviews with MCH and ECEC staff.DiscussionNutrition Now Phase 2 will break new ground by scaling up successively delivered and complementary dietary interventions in the first 1,000 days of life in a real-life context. The project also seeks to identify what level of implementation support is most effective when implementing digital, scalable, evidence-based early-life nutrition interventions in community settings. The project will inform implementation research and provide knowledge about effective implementation strategies to be used in a national scale-up of Nutrition Now.Trial registrationThe study is registered prospectively (submitted 14/06/2022, registration date: 19/06/2022) in the International Standard Randomised Controlled Trial Number registry (ISRCTN): reg. Number: ISRCTN10694967, https://doi.org/10.1186/ISRCTN10694967.

Yu-Qin Yan,1 Yu-Qing Huang,2 Ying-Qing Feng2 1Department of Cardiology, People’s Hospital of Shenzhen Baoan District, Shenzhen, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of ChinaCorrespondence: Yu-Qin Yan, Department of Cardiology, People’s Hospital of Shenzhen Baoan District, No. 118, Longjing Second Road, Xinan Street, Baoan District, Shenzhen, 518100, People’s Republic of China, Tel/Fax +86-755-27788311, Email graceyuqin@163.comBackground: The Great Chinese Famine, as the famine of 1959– 1961 was often known. Famine exposure during early life was proven to be associated with some kidney diseases but has not been studied with kidney stone. We aimed to investigate the relationship between exposure to the Great Chinese Famine in early life and the incidence of kidney stone in adulthood.Methods: From 1 January 2017 to 31 December 2018, a total of 19,658 eligible adults were recruited in a cross-sectional survey who were born between 1 October 1952 and 30 September 1964 in Guangdong, China. Participants were separated into kidney stone and none-kidney stone groups based on kidney stone status. According to birth data, participants were divided into non-exposed, fetal-exposed, early-, mid-, and late-childhood-exposed groups. Multivariate logistic regression, subgroup analysis and interaction test were used to estimate the odds ratios (ORs) and confidence intervals (CIs) between famine exposure and kidney stone.Results: In total, 19,658 (12,246 female, mean age 59.31 ± 3.68 years) subjects were enrolled, and 3219 (16.38%) participants with kidney stone. The prevalence of kidney in none-, fetal-, early-, mid-, and late-childhood-exposed groups were 645 (14.9%), 437 (15.9%), 676 (16.3%), 743 (17.0%), and 718 (17.6%), respectively (P< 0.001). When compared with the unexposed group, the fully adjusted ORs for kidney stone from fetal-exposed, early-, mid- to late-childhood-exposed groups were 1.37 (95% CI: 1.13, 1.68, P=0.002), 1.98 (95% CI: 1.45, 2.72, P< 0.001), 2.94 (95% CI: 1.96, 4.42, P< 0.001), and 3.48 (95% CI: 2.11, 5.72, P< 0.001), respectively (P for trend< 0.001). Subgroup analyses revealed no interactions between the famine effect on kidney stones and body mass index, gender, smoking status, history of diabetes or hypertension (all P for interaction > 0.05).Conclusion: This study found that exposure to the Great Chinese Famine during early life was independently associated with the increased incidence of kidney stone in adulthood.Keywords: Great Chinese Famine, early life, famine exposure, adulthood, kidney stone

Abstract Background The effectiveness of insecticide-treated nets (ITNs) in preventing malaria in young children is well established. However, the long-term effects of early childhood ITN use on educational outcomes, fertility, and marriage in early adulthood are not well understood. Methods This study uses 22 years of longitudinal data from rural Tanzania to investigate the associations between early life ITN use and educational attainment, fertility and marriage in early adulthood. Unadjusted and adjusted logistic regression models were used to estimate the associations between early life ITN use and early adult outcomes (education, childbearing, and marriage), controlling for potential confounders, such as parental education, household asset quintiles, and year of birth. Analyses were conducted separately for men and women. Results A total of 6706 participants born between 1998 and 2000 were enrolled in the study between 1998 and 2003. By 2019 a total of 604 had died and a further 723 could not be found, leaving 5379 participants who were interviewed, among whom complete data were available for 5216. Among women, sleeping under a treated net at least half of the time during early childhood [“high ITN use”] was associated with a 13% increase in the odds of completing primary school (adjusted odds ratio (aOR) 1.13 [0.85, 1.50]) and with a 40% increase in the odds of completing secondary school (aOR 1.40 [1.11, 1.76]) compared with women sleeping less frequently under ITNs in early life (

Emerging evidence highlights the important impact of early-life exposures on cancer development later in life. The present study aimed to investigate the impacts of a high-fat diet in early life on the mammary microenvironment in relation to breast tumorigenesis. Forty-four female C57BL/6 mice were fed a low-fat diet (LF, 10 kcal% fat) or a high-fat diet (HF, 60 kcal% fat) for 8 weeks starting at ~4 weeks of age. Twenty-two mice were sacrificed immediately after an 8 week feeding, and the rest of mice were switched to a normal diet for maintenance (Lab Diet, #5P76) for additional 12 weeks. A panel of metabolic parameters, inflammatory cytokines, as well as tumorigenic Wnt-signaling target genes were analyzed. The HF diet increased body weight and exacerbated mammary metabolic and inflammatory status. The disrupted microenvironment remains significant to the later life equivalent to young adulthood (p < 0.05). Mammary Wnt-signaling was elevated right after the HF diet as indicated by the upregulated expression of its downstream genes, whereas it was surprisingly suppressed after switching diets (p < 0.05). In summary, HF-induced overweight/obesity in early life altered the mammary metabolic and inflammatory microenvironments in favor of breast tumorigenesis, although its overall impact to breast cancer later in life warrants further investigation.

Abstract Background and objective Studies linking early life exposure to air pollution and subsequent impaired lung health have focused on chronic, low-level exposures in urban settings. We aimed to determine whether in utero exposure to an acute, high-intensity air pollution episode impaired lung function 7-years later. Method We conducted a prospective cohort study of children who lived in the vicinity of a coalmine fire. Respiratory function was measured using the forced oscillation technique (FOT). Z-scores for resistance at 5 Hz (R5), reactance at 5 Hz (X5) and area under the reactance curve (AX) were calculated. Two sets of analyses were conducted to address two separate questions: (1) whether mine fire exposure (a binary indicator; conceived after the mine fire vs in utero exposed) was associated with the respiratory Z-scores; (2) whether there was any dose–response relationship between fire-related PM2.5 exposure and respiratory outcomes among those exposed. Results Acceptable lung function measurements were obtained from 79 children; 25 unexposed and 54 exposed in utero. Median (interquartile range) for daily average and peak PM2.5 for the exposed children were 4.2 (2.6 – 14.2) and 88 (52—225) µg/m3 respectively. There were no detectable differences in Z-scores between unexposed and exposed children. There were no associations between respiratory Z-scores and in utero exposure to PM2.5 (daily average or peak). Conclusion There was no detectable effect of in utero exposure to PM2.5 from a local coalmine fire on post-natal lung function 7-years later. However, statistical power was limited.

Abstract Background Agaricus subrufescens is considered as one of the most important culinary-medicinal mushrooms around the world. It has been widely suggested to be used for the development of functional food ingredients to promote human health ascribed to the various properties (e.g., anti-inflammatory, antioxidant, and immunomodulatory activities). In this context, the interest in A. subrufescens based feed ingredients as alternatives for antibiotics has also been fuelled during an era of reduced/banned antibiotics use. This study aimed to investigate the effects of a fermented feed additive -rye overgrown with mycelium (ROM) of A. subrufescens—on pig intestinal microbiota, mucosal gene expression and local and systemic immunity during early life. Piglets received ROM or a tap water placebo (Ctrl) perorally every other day from day 2 after birth until 2 weeks post-weaning. Eight animals per treatment were euthanized and dissected on days 27, 44 and 70. Results The results showed ROM piglets had a lower inter-individual variation of faecal microbiota composition before weaning and a lower relative abundance of proteobacterial genera in jejunum (Undibacterium and Solobacterium) and caecum (Intestinibacter and Succinivibrionaceae_UCG_001) on day 70, as compared to Ctrl piglets. ROM supplementation also influenced gut mucosal gene expression in both ileum and caecum on day 44. In ileum, ROM pigs showed increased expression of TJP1/ZO1 but decreased expression of CLDN3, CLDN5 and MUC2 than Ctrl pigs. Genes involved in TLR signalling (e.g., TICAM2, IRAK4 and LY96) were more expressed but MYD88 and TOLLIP were less expressed in ROM pigs than Ctrl animals. NOS2 and HIF1A involved in redox signalling were either decreased or increased in ROM pigs, respectively. In caecum, differentially expressed genes between two groups were mainly shown as increased expression (e.g., MUC2, PDGFRB, TOLLIP, TNFAIP3 and MYD88) in ROM pigs. Moreover, ROM animals showed higher NK cell activation in blood and enhanced IL-10 production in ex vivo stimulated MLN cells before weaning. Conclusions Collectively, these results suggest that ROM supplementation in early life modulates gut microbiota and (local) immune system development. Consequently, ROM supplementation may contribute to improving health of pigs during the weaning transition period and reducing antibiotics use.

Abstract Background Ruminal microbiota in early life plays critical roles in the life-time health and productivity of ruminant animals. However, understanding of the relationship between gut microbiota and ruminant phenotypes is very limited. Here, the relationship between the rectum microbiota, their primary metabolites, and growth rate of a total of 76 young dairy goats (6-month-old) were analyzed, and then 10 goats with the highest or lowest growth rates respectively were further compared for the differences in the rectum microbiota, metabolites, and animal’s immune parameters, to investigate the potential mechanisms by which the rectum microbiota contributes to the health and growth rate. Results The analysis of Spearman correlation and microbial co-occurrence network indicated that some keystone rectum microbiota, including unclassified Prevotellaceae, Faecalibacterium and Succinivibrio, were the key modulators to shape the rectum microbiota and closely correlated with the rectum SCFA production and serum IgG, which contribute to the health and growth rate of young goats. In addition, random forest machine learning analysis suggested that six bacterial taxa in feces could be used as potential biomarkers for differentiating high or low growth rate goats, with 98.3% accuracy of prediction. Moreover, the rectum microbiota played more important roles in gut fermentation in early life (6-month-old) than in adulthood stage (19-month-old) of goats. Conclusion We concluded that the rectum microbiota was associated with the health and growth rate of young goats, and can be a focus on the design of the early-life gut microbial intervention.

Abstract The early life programming of adult health and disease (Developmental Origins of Adult Health and Disease; DOHaD) concept has attracted increased attention during recent years. In this review evidence is presented for epidemiological associations between early life factors (birth weight, prematurity) and cardiometabolic traits and risk of disease in adult life. Even if not all studies concur, the evidence in general is supporting such links. This could be due to either nature or nurture. There is evidence to state that genetic markers influencing birth weight could also be of importance for offspring hypertension or risk of coronary heart disease, this supporting the nature argument. On the other hand, several studies, both historical and experimental, have found that the change of maternal dietary intake or famine in pregnancy may cause permanent changes in offspring body composition as well as in hemodynamic regulation. Taken together, this also supports the strategy of preventive maternal and child health care, starting already during the preconception period, for lowering the risk of adult cardiometabolic disease in the affected offspring. Further studies are needed to better understand the mediating mechanisms, for example concerning arterial function, hemodynamic regulation, renal function, and neuroendocrine influences, related to the development of early vascular aging (EVA) and cardiovascular disease manifestations.

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.

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.

Ruminants’ milk is commonly used for supplying nutrients to infants when breast milk is unavailable or limited. Previous studies have highlighted the differences between ruminants’ milk composition, digestion, absorption, and fermentation. However, whether consuming different ruminants’ milk impact the appearance of the circulatory blood metabolites in the early postnatal life is not well understood. The analysis conducted here aimed to determine the effect of feeding exclusively whole milk from bovine, caprine or ovine species to pigs, approximately 7 days-old for 15 days, on circulatory blood plasma metabolites. Relative intensities of plasma metabolites were detected using a liquid chromatography-mass spectrometry based metabolomic approach. Seven polar and 83 non-polar (lipids) metabolites in plasma were significantly different (false discovery rate

The impact of prenatal maternal mental health on offspring socioemotional development is substantial and enduring. Existing literature primarily focuses on the effects of psychological distress during pregnancy, emphasizing adverse child outcomes. Recent studies, however, highlight the unique impact of positive maternal mental health on child outcomes. To elucidate the differential associations of maternal psychological distress and positive mental health during pregnancy with child outcomes, we conducted a systematic literature search and random-effects meta-analyses on studies investigating the associations of prenatal maternal mental health with child socioemotional development. Our analyses, comprising 74 studies with 321,966 mother-child dyads across 21 countries, revealed significant associations of prenatal psychological distress with both adverse and positive child socioemotional outcomes. Notably, the effect sizes for the association of psychological distress with positive child outcomes were smaller compared to adverse outcomes. Positive prenatal mental health, on the other hand, was significantly associated with positive socioemotional outcomes but not adverse outcomes. This meta-analysis highlights the independence of negative and positive prenatal mental health constructs and their distinct relationships with child socioemotional development. The findings underscore the importance of considering the positive spectrum of maternal mental health and developmental outcomes to enhance our understanding of prenatal influences on child development. Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335227, identifier CRD42022335227.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder worldwide. Extensive research has identified multiple factors contributing to its development, including genetic predisposition, chronic infection, gut dysbiosis, aberrant serotonin metabolism, and brain dysfunction. Recent studies have emphasized the critical role of the early life stage as a susceptibility window for IBS. Current evidence suggests that diet can heighten the risk of IBS in offspring by influencing the microbiota composition, intestinal epithelium structure, gene expression, and brain-gut axis. The use of antibiotics during pregnancy and the neonatal period disrupts the normal gut microbiota structure, aligning it with the characteristics observed in IBS patients. Additionally, early life stress impacts susceptibility to IBS by modulating TLR4, NK1, and the hypothalamic-pituitary-adrenal (HPA) axis while compromising the offspring's immune system. Formula feeding facilitates the colonization of pathogenic bacteria in the intestines, concurrently reducing the presence of probiotics. This disruption of the Th1 and Th2 cell balance in the immune system weakens the intestinal epithelial barrier. Furthermore, studies suggest that delivery mode influences the occurrence of IBS by altering the composition of gut microbes. This review aims to provide a comprehensive summary of the existing evidence regarding the impact of adverse early life exposures on IBS during pregnancy, intrapartum, and neonatal period. By consolidating this knowledge, the review enhances our understanding of the direct and indirect mechanisms underlying early life-related IBS and offers new insights and research directions from childhood to adulthood.

Early bacterial colonization and succession within the gastrointestinal tract have been suggested to be crucial in the development of host immunity. In this study, we have investigated the changes in live weight and concentrations of selected serum parameters in relation to their fecal bacterial communities as determined by high throughput sequencing of the 16S rRNA gene over the same period in lambs. The results showed that lambs’ growth performance, the serum parameters, fecal bacterial community and fecal bacterial functions were all affected (P

Abstract Background Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk. Methods We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants. Results Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98–1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00–1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04–1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77–1.22) and colon cancer (OR: 0.97, 95% CI: 0.76–1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90–1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05). Conclusions Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.

Abstract Background The gastrointestinal tract (GIT) microbiome of ruminants and its metabolic repercussions vastly influence host metabolism and growth. However, a complete understanding of the bidirectional interactions that occur across the host-microbiome axis remains elusive, particularly during the critical development stages at early life. Here, we present an integrative multi-omics approach that simultaneously resolved the taxonomic and functional attributes of microbiota from five GIT regions as well as the metabolic features of the liver, muscle, urine, and serum in sika deer (Cervus nippon) across three key early life stages. Results Within the host, analysis of metabolites over time in serum, urine, and muscle (longissimus lumborum) showed that changes in the fatty acid profile were concurrent with gains in body weight. Additional host transcriptomic and metabolomic analysis revealed that fatty acid β-oxidation and metabolism of tryptophan and branched chain amino acids play important roles in regulating hepatic metabolism. Across the varying regions of the GIT, we demonstrated that a complex and variable community of bacteria, viruses, and archaea colonized the GIT soon after birth, whereas microbial succession was driven by the cooperative networks of hub populations. Furthermore, GIT volatile fatty acid concentrations were marked by increased microbial metabolic pathway abundances linked to mannose (rumen) and amino acids (colon) metabolism. Significant functional shifts were also revealed across varying GIT tissues, which were dominated by host fatty acid metabolism associated with reactive oxygen species in the rumen epithelium, and the intensive immune response in both small and large intestine. Finally, we reveal a possible contributing role of necroptosis and apoptosis in enhancing ileum and colon epithelium development, respectively. Conclusions Our findings provide a comprehensive view for the involved mechanisms in the context of GIT microbiome and ruminant metabolic growth at early life. Video Abstract

This meta-analysis aimed to investigate the correlation between early-life antibiotic use and allergic rhinitis. PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for available studies. Eighteen studies covering 1,768,874 children were included. Early-life antibiotics were associated with an increased incidence of allergic rhinitis (effect size (ES) = 5.00, 95% confidence interval [CI]: 4.88–5.13; I 2 = 95.7%, P heterogeneity

Abstract Background The palatine tonsils are part of the mucosal immune system and stimulate immune responses through M cell uptake sampling of antigens and bacteria in the tonsillar crypts. Little is known about the development of the tonsillar microbiota and the factors determining the establishment and proliferation of disease-associated bacteria such as Streptococcus suis. In this study, we assessed tonsillar microbiota development in piglets during the first 5 weeks of life and identified the relative importance of maternal and environmental farm parameters influencing the tonsillar microbiota at different ages. Additionally, we studied the effect sow vaccination with a bacterin against S. suis on microbiota development and S. suis colonisation in their offspring. Results Amplicon sequencing of the 16S rRNA gene V3-V4 region revealed that a diverse tonsillar microbiota is established shortly after birth, which then gradually changes during the first 5 weeks of life without a large impact of weaning on composition or diversity. We found a strong litter effect, with siblings sharing a more similar microbiota compared to non-sibling piglets. Co-housing in rooms, within which litters were housed in separate pens, also had a large impact on microbiota composition. Sow parity and prepartum S. suis bacterin vaccination of sows had weaker but significant associations with microbiota composition, impacting on the abundance of Streptococcus species before and after weaning. Sex and birthweight had limited impact on the tonsillar microbiota, and none of the measured factors had consistent associations with microbiota diversity. Conclusions The piglet tonsillar microbiota is established shortly after birth. While microbiota development is associated with both environmental and maternal parameters, weaning has limited impact on microbiota composition. Intramuscular vaccination of sows pre-partum had a significant effect on the tonsillar microbiota composition of their piglets. These findings provide new insights into the mechanisms shaping the tonsillar microbiota.

ObjectiveThe causal relationship between early life adiposity and gestational diabetes mellitus (GDM) and the underlying mechanisms remains unclear. This study aimed to investigate the independent causal association between early life adiposity and GDM and identify potential metabolic mediators and their mediating effects on this relationship.MethodsUsing genome-wide association study (GWAS) summary statistics from the publicly available database of early life adiposity (5,530 cases and 8,318 controls) and GDM (11,279 cases and 179,600 controls), a two-step, two-sample Mendelian randomization (MR) was conducted to estimate the causal mediation effects of lipidomic biomarkers including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, apolipoprotein A-Ι, and apolipoprotein B on the relationship between early life adiposity and GDM.ResultsGenetically predicted childhood adiposity was positively associated with risk of GDM (OR: 1.21, 95%CI: 1.09–1.34, p = 4.58 × 10−4). This causal relationship remained after accounting for adult adiposity traits in the multivariable MR analyses. Two-step MR identified three candidate mediators that partially mediated the effect of early life adiposity on GDM, including HDL-C (5.81, 95%CI: 3.05–8.57%), apolipoprotein A-Ι (4.16, 95%CI: 1.64–6.69%), and triglyceride (2.20, 95%CI: 0.48–3.92%).ConclusionThis MR study demonstrated that the causal effect of childhood obesity on future GDM risk was independent of adult adiposity. We identified three mediators, including HDL-C, apolipoprotein A-Ι, and triglyceride, in this association pathway. Our results provide insights into the pathogenesis of GDM and suggest additional prevention and treatment targets for GDM related to early life adiposity.