Infections In Early Life Research Articles

Bifidobacterium breve M-16V and scGOS/lcFOS Supplementation to Dams Ameliorates Infant Rotavirus Infection in Early Life.

The immune system of newborns is underdeveloped, leaving them susceptible to infections like rotavirus (RV). Despite vaccines, RV remains a leading cause of child mortality, especially in developing countries. Maternal immunity is transferred during pregnancy and breastfeeding to the offspring providing protection against RV infection. This study aims to explore how the maternal diet can enhance the newborn's ability to fight early infections. Pregnant rats received orally Bifidobacterium breve M-16V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosaccharides (lcFOS). At day 5 of life pups are infected with RV and at day 8, samples are collected for the infection analysis. Pups whose mothers received the synbiotic have lower RV infection severity. The levels of immunoglobulins (Ig) IgG2c and IgA are raised in pups' plasma and digested milk, respectively. Synbiotic supplementation improves intestinal maturation and increases gene expression of immune-related genes. In conclusion, the administration of this synbiotic to gestating and lactating mothers ameliorates the incidence and severity of the pup's diarrhea caused by the RV infection by improving their immunity.

Housing tenure and acute lower respiratory tract infection admissions in two Scottish birth cohorts

Abstract Introduction Early-life acute lower respiratory tract infections (LRTI) have been associated with increased morbidity and mortality. Despite young children spending much of their time at home, the contribution of home ownership status, on LRTI hospital admissions is unknown. Objectives To estimate the association between housing tenure and the odds of LRTI hospitalization in children <2 years in two birth cohorts. Methods De-identified Scottish birth records were linked to maternal Census data (2001 and 2011) and to hospital admission data to construct two birth cohorts (Cohort 1 (C1), born 2000-2002; Cohort 2 (C2), 2010-2012). Using logistic regression we estimated the association of housing tenure (owned, social rented, private rented, rent-free) with the odds of LRTI hospital admission, before and after adjustment for maternal age, residential area, and maternal qualification level. Results Over the 2-year follow-up, there were 14,833 LRTI admissions in 12,527 children (10,832 children had 1 LRTI admission and 1,695 >1 LRTI admission). 75.6 % of all LRTI admissions were due to bronchiolitis. In C1 and C2, 4.0% and 5.3% children, respectively, had one or more LRTI admission. Compared to children living in owned housing, the odds of LRTI admission were higher in children living in social rented housing (C1: Odds ratio=1.40, 95% confidence interval: 1.31-1.49; C2: 1.23, 1.16-1.31), private rented (C1:1.24, 1.11,1.39; C2: 1.14, 1.06-1.21), and rent-free housing (C1: 1.53, 1.35,1.74; C2: 1.04, 0.80-1.36) after confounder adjustment. Conclusions We found an association between non-owned housing and higher odds of LRTI admission which was more marked in C1 than in C2. Further research is warranted to unpick the mechanisms underlying the association between housing tenure and LRTI admission. Interventions to prevent LRTI admissions could usefully target children living in non-owned housing. Key messages • This study demonstrates the value of administrative and health data linkage in improving our understanding of how socio-environmental factors might impact children’s respiratory health. • Children living in social and private rented housing (compared to owned housing) have a higher risk of LRTI hospital admission and could benefit the most from LRTI-lowering interventions.

Early-Life Infections, Antibiotics and Later Risk of Childhood and Early Adult-Onset Inflammatory Bowel Disease: Pooled Analysis of Two Scandinavian Birth Cohorts.

Childhood antibiotic use has been associated with inflammatory bowel disease (IBD), although the potential contribution of infection frequency remains uncertain. To explore the association between early-life infections, antibiotics and IBD development. We used population-based data from ABIS (Sweden) and MoBa (Norway) cohorts following children from birth (1997-2009) until 2021. Prospectively collected questionnaires identified infection frequency (any, gastrointestinal and respiratory) and antibiotics (any, penicillin and non-penicillin) until age 3. IBD diagnosis required ≥ 2 records in national health registries. Cohort-specific hazard ratios (aHR), adjusted for parental education, smoking and IBD were estimated and pooled using a random-effects model. Antibiotic analyses were adjusted for infection frequency. There were 103,046 children (11,872 ABIS and 91,174 MoBa), contributing to 1,663,898 person-years of follow-up, during which 395 were diagnosed with IBD. The frequency of any infection at 0 to < 1 and 1 to < 3 years showed a pooled aHR of 1.01 (95% confidence interval [CI] = 0.96-1.07) and 1.00 (95% CI = 0.99-1.01) per additional infection for IBD. Adjusting for infections, any versus no antibiotics in the first year was associated with IBD (pooled aHR = 1.33 [95% CI = 1.01-1.76]). The aHR for additional antibiotic course was 1.17 (95% CI = 0.96-1.44), driven by penicillin (per additional course, aHR = 1.28 [95% CI = 1.02-1.60]). Although antibiotics at 1 to < 3 years did not show an association with IBD or Crohn's disease, non-penicillin antibiotics were associated with ulcerative colitis (per additional course, aHR = 1.95 [95% CI = 1.38-2.75]). Early-life antibiotic use was, a significant risk factor for childhood and early adult-onset IBD, independent of infection frequency.

Early-Life Respiratory Syncytial Virus (RSV) Infection Triggers Immunological Changes in Gut-Associated Lymphoid Tissues in a Sex-Dependent Manner in Adulthood.

Severe respiratory syncytial virus (RSV) infection during early life has been linked to gut dysbiosis, which correlates with increased disease severity and a higher risk of developing asthma later in life. However, the impact of such early-life RSV infections on intestinal immunity in adulthood remains unclear. Herein, we show that RSV infection in 3-week-old mice induced persistent differential natural killer (NK) and T cell profiles within the lungs and gastrointestinal (GI) lymphoid tissues (GALT) in adulthood. Notably, male mice exhibited more pronounced RSV-induced changes in immune cell populations in both the lungs and GALT, while female mice displayed greater resilience. Importantly, early-life RSV infection was associated with the chronic downregulation of CD69-expressing T lymphocytes, particularly T regulatory cells in Peyer's patches, which could have a significant impact on T cell functionality and immune tolerance. We propose that RSV infection in early life is a trigger for the breakdown in immune tolerance at mucosal surfaces, with potential implications for airways allergic disease, food allergies, and other GI inflammatory diseases.

Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination.

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, and markedly influencing serum cytokine and total antibody levels. Beyond changes in the immune responses, these exposures also modulated the composition of the endogenous intestinal microbiota. Although sequentially-infected mice exhibited increased systemic immune activation and T cell responses after intramuscular and intranasal SARS-CoV-2 immunization, we observed decreased vaccine-induced antibody responses in these animals. These results suggest that early-life viral exposures are sufficient to diminish antibody responses to vaccination in mice, and highlight the potential importance of considering prior microbial exposures when investigating vaccine responses.

Helicobacter pylori seropositivity associates with hyperglycemia, but not obesity, in Danish children and adolescents

BackgroundHelicobacter pylori colonizes the human stomach and may affect the inflammatory response, hormone production related to energy regulation, and gastrointestinal microbiota composition. Previous studies have explored a potential association between H. pylori infection and pediatric obesity with varying results. Considering the immunomodulatory effects of early-life infection with H. pylori that can confer beneficial effects, we hypothesized that we would find an inverse relationship between H. pylori seropositivity and obesity among Danish children and adolescents.MethodsWe assessed H. pylori seroprevalence in 713 subjects from an obesity clinic cohort and 990 subjects from a population-based cohort, aged 6 to 19 years, and examined its association with obesity and other cardiometabolic risk factors.ResultsNo association was found between H. pylori and body mass index standard deviation score (BMI SDS). H. pylori seropositivity was, however, significantly associated with higher fasting plasma glucose levels and the prevalence of hyperglycemia.ConclusionWhile we did not find an association between H. pylori seropositivity and BMI SDS, we observed a significant association with higher fasting plasma glucose levels and increased prevalence of hyperglycemia, suggesting that H. pylori infection may contribute to impaired glucose regulation in Danish children and adolescents.Graphical abstract

From Womb to World: Immunological Pathways Influencing Stunting and 2030 Sustainability

Stunting affects 150 million children globally, indicating an existing inequality in nutrition and health; despite focusing on nutrient deficiencies, the immunological continuum from prenatal to postnatal needs to be better described. This study synthesized the literature analyzing the role of immune functions in stunting from prenatal to early childhood and its implications for the 2030 Sustainable Development Goals. The database search was performed on PubMed, Scopus, Web of Science, and Google Scholar, in accordance with the PRISMA 2020 guidelines. The objective of the current narrative review was to determine immunological factors and stunting using peer-reviewed English research published from 2000 to 2024. The review also reveals that stunting is a complex process involving immune and nutritional factors, but the significant determinants of growth are prenatal immune priming and early-life infection. Some findings are related to the knowledge of the interrelation between nutritional deficiencies and immune system dysfunctions, cytokine patterns, and gut microbiota dynamics. Thus, this study provides a general definition of stunting and recommends additional research in immunology and the need for public health measures involving nutritional and immunological interventions. The assessment provides recommendations for preventing stunting and ensures that the actions are aligned with the 2030 Sustainable Development Goals for improving children’s well-being.

Asthma development is associated with low mucosal IL-10 during viral infections in early life.

Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting. To investigate insitu virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma. We included 493 episodes of acute respiratory illnesses in 277 children aged 0-3 years from the COPSAC2010 mother-child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high-sensitivity MesoScale Discovery kits and compared between children with and without viral PCR-identification in nasopharyngeal samples. Finally, we investigated whether the virus-specific immune response was associated with asthma by age 6 years. Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-ɣ, TNF-α, CCL4, CXCL10 and IL-10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL-10 (FDR <0.05) during viral episodes compared to children not developing asthma. We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL-10) immune mediator level. This provides insight into the interplay between early-life viral infections, airway immunity and asthma development.

EarlyLife - Gut epithelial dynamics and function at the nexus of early life infection and longterm health

We spoke with Prof. Dr. Mathias Hornef about the ERC-funded EarlyLife project, which investigates how early-life infections impact the gut epithelium, microbiome, and immune system development in neonates. Using advanced techniques and mouse models, the project aims to uncover the influence of these infections on long-term health and disease susceptibility.

Sex Differences in Hepatic Inflammation, Lipid Metabolism, and Mitochondrial Function Following Early Lipopolysaccharide Exposure in Epileptic WAG/Rij Rats.

Among the non-communicable neurological diseases, epilepsy is characterized by abnormal brain activity with several peripheral implications. The role of peripheral inflammation in the relationship between seizure development and nonalcoholic fatty liver disease based on sex difference remains still overlooked. Severe early-life infections lead to increased inflammation that can aggravate epilepsy and hepatic damage progression, both related to increased odds of hospitalization for epileptic patients with liver diseases. Here, we induced a post-natal-day 3 (PND3) infection by LPS (1 mg/kg, i.p.) to determine the hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45). We evaluated intra- and inter-gender differences in systemic and liver inflammation, hepatic lipid dysmetabolism, and oxidative damage related to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Endotoxin challenge triggered a more severe inflammatory and immune response in male epileptic rats, compared to females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-treated female rats showed significant alterations in systemic and hepatic lipid profiles and reduced mitochondrial fatty acid oxidation. The two different sex-dependent mechanisms of LPS-induced liver injury converge in increased ROS production and related mitochondrial oxidative damage in both sexes. Notably, a compensatory increase in antioxidant defense was evidenced only in female rats. Our study with a translational potential demonstrates, for the first time, that early post-natal infections in epileptic rats induced or worsened hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Effect of dry period immunization of Salmonella Dublin latent carriers with a commercial live culture vaccine on intrauterine transmission based on the presence of precolostral antibodies in offspring

Salmonella Dublin latent carrier cows represent a high risk for infection of newborn calves via intrauterine transmission and shedding of bacteria in feces and colostrum at calving. Vaccination of these latent carrier dams during late gestation boosts immunity against S. Dublin. This could reduce the activation of the dormant bacteria during the periparturient immune dysfunction period, thereby reducing the risk of early-life infection in the offspring. Thus, the objective of this study was to evaluate the extent to which vaccinating S. Dublin latent carrier cows at dry-off with a commercial live culture vaccine reduces bacterial shedding at calving and intrauterine infection to calves. To identify latent carriers, we screened 1,084 cows in 4 Michigan commercial dairy farms with a history of S. Dublin. Cows were defined as latent carriers when they showed 3 consecutive positive milk antibody ELISA tests conducted every 2 mo. Subsequently, 148 latent carriers were randomly allocated to the vaccine or control group. Vaccine cows received a commercial live culture vaccine subcutaneously (SC) at dry-off and a booster 2 weeks later. Control cows received saline SC at the same times. At calving, we collected fecal and colostrum samples from the dam and a pre-colostral serum sample from the calf. Bacterial shedding was evaluated in feces and colostrum both qualitatively and quantitatively through bacterial culture and qPCR, respectively. Intrauterine transmission was defined when a calf was positive for serum antibody ELISA at birth. Vaccination decreased the likelihood of calves being born S. Dublin seropositive (Relative Risk [95%CI]) = 0.19 [0.04 - 0.84]). However, no S. Dublin positive isolates were identified through either bacteriological culture or qPCR in feces or colostrum. Vaccination of S. Dublin latent-carrier cows at dry-off reduced intrauterine transmission to calves. Further research is warranted into the potential of vaccination to decrease vertical transmission of S. Dublin in dairy farms. Additionally, the absence of S. Dublin positive fecal and colostrum samples warrants further evaluation of the detection methods for identifying latent carriers or S. Dublin isolation, as well as the role of latent carriers in infecting newborn calves in the maternity area at birth.

Single cell profiling to determine influence of wheeze and early-life viral infection on developmental programming of airway epithelium.

Nasal airway epithelial cells from children with wheeze are characterized by altered development and increased susceptibility to RSV infection.

Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia

AbstractEpidemiological studies report opposing influences of infection on childhood B-cell acute lymphoblastic leukemia (B-ALL). Although infections in the first year of life appear to exert the largest impact on leukemia risk, the effect of early pathogen exposure on the fetal preleukemia cells (PLC) that lead to B-ALL has yet to be reported. Using cytomegalovirus (CMV) infection as a model early-life infection, we show that virus exposure within 1 week of birth induces profound depletion of transplanted E2A-PBX1 and hyperdiploid B-ALL cells in wild-type recipients and in situ–generated PLC in Eμ-ret mice. The age-dependent depletion of PLC results from an elevated STAT4-mediated cytokine response in neonates, with high levels of interleukin (IL)-12p40–driven interferon (IFN)-γ production inducing PLC death. Similar PLC depletion can be achieved in adult mice by impairing viral clearance. These findings provide mechanistic support for potential inhibitory effects of early-life infection on B-ALL progression and could inform novel therapeutic or preventive strategies.

Children born preterm or small for gestational age to mothers with multiple sclerosis: Do these children have an increased risk of infections in early life?

Background: Mothers with multiple sclerosis are at increased risk of preterm birth and small for gestational age infants. Both conditions pose a risk of morbidity, including early-life infections. Objective: This study aimed to assess the risk of infections in the first 3 years of life among children born preterm or small for gestational age to mothers with multiple sclerosis. Methods: We used Danish national health registers to establish the study cohort of all births by women with MS born from 1995 to 2023. In Cox regression models, we estimated hazard ratios (HRs) of infections in preterm or small for gestational age children. Results: Preterm children had an adjusted HR of 1.49 (95% confidence interval (95% CI) 1.15–1.93) for hospital-diagnosed infection and 0.88 (95% CI 0.72–1.06) for antibiotic prescriptions. Small for gestational age children had an adjusted HR of 0.81 (95% CI 0.54–1.22) for hospital-diagnosed infection and 1.07 (95% CI 0.82–1.38) for antibiotic prescriptions. Conclusion: Children born preterm to mothers with multiple sclerosis had an increased risk of hospital-diagnosed infections in the first 3 years of life, but not of mild-to-moderate infections evaluated on prescriptions. Children born small for gestational age did not have an increased risk of infections.

Determinants of lung function development from birth to age 5 years: an interrupted time series analysis of a South African birth cohort

Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort. We prospectively followed children enrolled in a population-based cohort from birth (between March 5, 2012 and March 31, 2015) to age 5 years with annual lung function assessment. Data on multiple early-life exposures, including LRTI, were collected. The effect of early-life risk factors on lung function development from birth to age 5 years was assessed using the Generalised Additive Models for Location, Scale and Shape and Interrupted Time Series approach. 966 children (475 [49·2%] female, 491 [50·8%] male) had lung function measured with oscillometry, tidal flow volume loops, and multiple breath washout. LRTI occurred in 484 (50·1%) children, with a median of 2·0 LRTI episodes (IQR 1·0-3·0) per child. LRTI was independently associated with altered lung function, as evidenced by lower compliance (0·959 [95% CI 0·941-0·978]), higher resistance (1·028 [1·016-1·041]), and higher respiratory rate (1·018 [1·063-1·029]) over 5 years. Additional impact on lung function parameters occurred with each subsequent LRTI. Respiratory syncytial virus (RSV) LRTI was associated with lower expiratory flow ratio (0·97 [0·95-0·99]) compared with non-RSV LRTI. Maternal factors including allergy, smoking, and HIV infection were also associated with altered lung development, as was preterm birth, low birthweight, female sex, and coming from a less wealthy household. Public health interventions targeting LRTI prevention, with RSV a priority, are vital, particularly in low-income and middle-income settings. UK Medical Research Council Grant, The Wellcome Trust, The Bill & Melinda Gates Foundation, US National Institutes of Health Human Heredity and Health in Africa, South African Medical Research Council, Hungarian Scientific Research Fund, and European Respiratory Society.

Burden and Subtypes of Early Life Infections Increase the Risk of Asthma

Early life respiratory tract infections have been linked to the development of asthma, but studies on the burden and subtypes of common infections in asthma development are sparse. To examine the association between burden of early life infections, including subtypes, with the risk of asthma from age 3 to 10 years and lung function at age 10 years. We included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, for whom infections such as colds, acute tonsillitis, acute otitis media, pneumonia, gastroenteritis, and fever were registered prospectively in daily diaries at age 0 to 3 years and asthma was diagnosed longitudinally from age 3 to 10 years. The association between the burden of infection and subtypes and risk of asthma was analyzed by generalized estimating equations. The children experienced a median of 16 infections (interquartile range, 12-23 infections) at age 0 to 3 years. Children with a high burden of infections (above the median) had an increased risk of asthma at age 3 to 10 years (adjusted odds ratio= 3.61; 95% CI, 2.39-5.45; P < .001), which was driven by colds, pneumonia, gastroenteritis, and fever episodes (P < .05) but not by acute otitis media and tonsillitis. Lower lung function measures at age 10 years were associated with the burden of pneumonia but not the overall infection burden. The association between colds and the risk of asthma was significantly higher in children with allergic rhinitis at age 6 years (P interaction= .032). A high burden of early life infections in terms of colds, pneumonia, gastroenteritis, and fever is associated with an increased risk of developing asthma, particularly in children with respiratory allergy. Strategies to diminish these early life infections may offer a path for the primary prevention of childhood asthma.

Infant microbes and metabolites point to childhood neurodevelopmental disorders

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.

Do early-life allergic sensitization and respiratory infection interact to increase asthma risk?

Objective The ‘two-hit’ hypothesis theorizes that early life allergic sensitization and respiratory infection interact to increase asthma risk. Methods We sought to determine in a high allergy risk birth cohort whether interactions between early life allergic sensitization and respiratory infection were associated with increased risk for asthma at ages 6–7 years and 18 years. Allergic sensitization was assessed at 6, 12, and 24 months by skin prick testing to 3 food and 3 aeroallergens. Respiratory infection was defined as reported “cough, rattle, or wheeze” and assessed 4-weekly for 15 months, at 18 months, and age 2 years. Regression analysis was undertaken with parent-reported asthma at age 6–7 years and doctor diagnosed asthma at 18 years as distinct outcomes. Interactions between allergic sensitization and respiratory infection were explored with adjustment made for potential confounders. Results Odds of asthma were higher in sensitized compared to nonsensitized children at age 6–7 years (OR = 14.46; 95% CI 3.99–52.4), There was no evidence for interactions between allergic sensitization and early life respiratory infection, with a greater frequency of respiratory infection up to 2 years of age associated with increased odds for asthma at age 6–7 years in both sensitized (OR = 1.13; 95% CI 1.02–1.25, n = 199) and nonsensitized children (OR = 1.31; 1.11–1.53, n = 211) (p interaction = 0.089). At age 18 years, these associations were weaker. Conclusions Our findings do not support ‘two-hit’ interactions between early life allergic sensitization and respiratory infection on asthma risk. Both early life respiratory infections and allergic sensitization were risk factors and children with either should be monitored closely for development of asthma.

The microbiota-gut-brain axis: A crucial immunomodulatory pathway for Bifidobacterium animalis subsp. lactis' resilience against LPS treatment in neonatal rats

An imbalanced gut microflora may contribute to immune disorders in neonates due to an immature gut barrier. Bacterial toxins, particularly, can trigger the immune system, potentially resulting in uncontrolled gut and systemic inflammation. Previous research has revealed that Bifidobacterium animalis subsp. lactis (B. lactis) could protect against early-life pathogen infections by enhancing the gut barrier. However, the effects of B. lactis on a compromised immune system remain uncertain. Hence, this study concentrated on the immunomodulatory effects and mechanisms of B. lactis in neonatal rats intraperitoneally injected with lipopolysaccharide (LPS), a bacterial toxin and inflammatory mediator. First, B. lactis significantly alleviated the adverse effects induced by LPS on the growth, development, and body temperature of neonatal rats. Second, B. lactis significantly reduced the immune responses and damage induced by LPS, affecting both systemic and local immune responses in the peripheral blood, gut, and brain. Notably, B. lactis exhibited extra potent neuroprotective and neurorepair effects. Our research found that pre-treatment with B. lactis shaped the diverse gut microecology by altering both microbial populations and metabolic biomolecules, closely linked to immunomodulation. Overall, this study elucidated the multifaceted roles of B. lactis in neonatal hosts against pathogenic infection and immune disorder, revealing the existence of the microbiota-gut-brain axis.

Early-life influenza A (H1N1) infection independently programs brain connectivity, HPA AXIS and tissue-specific gene expression profiles

Early-life adversity covers a range of physical, social and environmental stressors. Acute viral infections in early life are a major source of such adversity and have been associated with a broad spectrum of later-life effects outside the immune system or “off-target”. These include an altered hypothalamus–pituitary–adrenal (HPA) axis and metabolic reactions. Here, we used a murine post-natal day 14 (PND 14) Influenza A (H1N1) infection model and applied a semi-holistic approach including phenotypic measurements, gene expression arrays and diffusion neuroimaging techniques to investigate HPA axis dysregulation, energy metabolism and brain connectivity. By PND 56 the H1N1 infection had been resolved, and there was no residual gene expression signature of immune cell infiltration into the liver, adrenal gland or brain tissues examined nor of immune-related signalling. A resolved early-life H1N1 infection had sex-specific effects. We observed retarded growth of males and altered pre-stress (baseline) blood glucose and corticosterone levels at PND42 after the infection was resolved. Cerebral MRI scans identified reduced connectivity in the cortex, midbrain and cerebellum that were accompanied by tissue-specific gene expression signatures. Gene set enrichment analysis confirmed that these were tissue-specific changes with few common pathways. Early-life infection independently affected each of the systems and this was independent of HPA axis or immune perturbations.