Early Life Antibiotic Research Articles

Early-life antibiotic usage and impact on the gut microbiota, including emergence of antimicrobial resistant Enterococcus

The early-life microbiota is an ‘immature’ and highly dynamic microbial ecosystem, which is central to infant health. Both perinatal and postnatal factors can impact the gut microbiota, with antibiotics proposed to cause short and longer-term disturbances. Antibiotics not only impact microbial community composition but also contribute to the overall antibiotic resistance profile, i.e. the ‘resistome’, and they may also enhance carriage of multi-drug-resistant bacteria. Given high antibiotic prescription practices in pregnant women and newborns this also contributes to the global threat of antimicrobial resistance. This review summarises the current literature on antibiotic usage and how this may impact the developing gut microbiota during early-life, including the influence of horizontal gene transfer on contributions to pathogenicity and resistance of gut bacteria. We also focus on Enterococcus spp. given their high levels in infants and their link with opportunistic infections that are a significant cause of morbidity and mortality during early-life. Finally, a perspective on the importance to antibiotic stewardship, and harnessing the microbiota itself for anti-infection therapies for reducing antibiotic usage are also covered.

Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study

ObjectivesEarly antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics...

Early-life prophylactic antibiotic treatment disturbs the stability of the gut microbiota and increases susceptibility to H9N2 AIV in chicks

BackgroundAntibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment.ResultsUnexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection.ConclusionsOur data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management.Ao91n5eHkkQPyDkUXXsk_bVideo

Early Life Antibiotic Exposures Inhibits Postnatal Enteric Nervous System Maturation and Alters Neonatal Neuroimmune Interactions

Abstract The enteric nervous system (ENS) regulates intestinal homeostasis via interactions with smooth muscle, epithelium, and immune cells. To assess the impact of early life antibiotics on postnatal ENS development, we performed neuron specific translating ribosome affinity purification to isolate RNA from control and antibiotic exposed enteric neurons for RNA sequencing. Colonic enteric neurons from antibiotic exposed pre-weaning mice expressed significantly less mature neuron markers, and acquired a more inflammatory cytokine signaling signature (e.g. IL18, MCP-1, TLR4). Immunofluorescence staining and ELISA revealed increased enteric neuron density in antibiotic exposed colons, yet reduced expression of neuronal markers including Tuj1 (neuron specific tubulin), synaptophysin (synapse marker) and acetylcholine. Notably, antibiotics did not affect ENS development in germ free mice. By confocal microscopy, antibiotic exposure appeared to reduce phagocytosis of neuronal cell bodies by macrophages, but phagocytosis of synapses by macrophages was increased. Flow cytometry revealed that antibiotic exposure reduced the proportion of macrophages expressing the “M2” marker CD163 compared to controls. This observation is reminiscent of Hirschsprung disease (HSCR), a congenital absence of the ENS from the distal intestine, which causes intestinal macrophages to adopt a pro-inflammatory phenotype and predisposes patients for HSCR-associated enterocolitis secondary to decreased cholinergic signaling. These data suggest that early life antibiotic exposure disrupts how macrophages participate in postnatal ENS development in a microbiota dependent mechanism. NIH NIAID U01AI131342, NIH NIDDK P30DK052574, T32DK077653, NIH T32HD43010 American Academy of Pediatrics Marshall Klaus 2022

Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study.

Antibiotics represent the most common type of medication used during pregnancy and infancy. Antibiotics have been proposed as a possible factor in changes in microbiota composition, which may play a role in the aetiology of autism and attention deficit/hyperactivity disorder (ADHD). Our aim was to investigate the association between maternal and early-life antibiotic use and autism and ADHD in childhood. This Swedish nation-wide population-based cohort study included all first live singleton births (N = 483,459) between January 2006 and December 2016. The association of dispensed antibiotics with autism and ADHD in children aged ≤ 11 years was estimated by applying multivariable logistic regression and generalised estimating equations models. Of the mothers, 25.9% (n = 125,106) were dispensed ≥1 antibiotic during the exposure period (from 3 months pre-conception to delivery), and 41.6% (n = 201,040) of the children received ≥ 1 antibiotic in early life (aged ≤ 2 years). Penicillin was the most prescribed antibiotic class (17.9% of mothers, 38.2% of children). Maternal antibiotic use was associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.09-1.23] and ADHD (OR = 1.29, 95% CI 1.21-1.36) in childhood. Early-life exposure to antibiotics showed an even stronger association [autism (OR = 1.46, 95% CI 1.38-1.55); ADHD (OR = 1.90, 95% CI 1.80-2.00)]. Both maternal and childhood-exposure sub-analyses suggested a dose-response relationship. Maternal and early-life antibiotic use was associated with an increased risk of autism and ADHD in childhood. However, differences were noted by exposure period and antibiotic classes.

274 Early life antibiotic exposure and genetic risk in neurodevelopmental disorders: effects on neurogenesis, the gut microbiome, and behavior

OBJECTIVES/GOALS: Our long-term goal is to understand how both genetic and environmental (GxE) factors contribute to neurodevelopmental disorders (NDDs) so that we may potentially intervene in disease pathogenesis and design therapies to address functional deficiencies. METHODS/STUDY POPULATION: Our studies use a novel GxE model to determine how cephalosporin antibiotic exposure alters the gut microbiome, hippocampal neurogenesis, and behavior in the genetically vulnerable 16p11.2 microdeletion (16pDel) mouse. This mouse models one of the most frequently observed genetic risk variants implicated in NDDs, including ~1% of autism diagnoses. Wildtype and 16pDel littermates were exposed to saline or the cephalosporin, cefdinir, from postnatal days 5-9. We quantified changes in gut microbiota composition using 16S rRNA gene sequencing and utilized immunoblotting, immunohistochemistry, and bulk RNA gene sequencing to assess changes in hippocampal neurogenesis. An additional cohort of saline or cefdinir-exposed mice were subjected to a behavioral battery to assess changes in sociability and anxiety. RESULTS/ANTICIPATED RESULTS: We leveraged the next-generation microbiome bioinformatics platform, Quantitative Insights Into Microbial Ecology 2 (QIIME2) to analyze 16S rRNA gene sequencing datasets of P13 cecal samples from saline- and cefdinir-exposed mice. We found successful perturbations to the gut microbiome following early life cefdinir exposure. Further, we found a robust 50% reduction in hippocampal cyclin E protein in cefdinir-exposed 16pDel male mice, which was replicated in a second independent experiment. This reduction extended to the S-phase cell entry and general stem cell population, quantified by EdU+ and Ki67+ cell numbers, respectively. Lastly, in our first cohort of mice for behavioral studies, we found reduced sociability and increased anxiety-like behaviors in cefdinir-exposed mice. DISCUSSION/SIGNIFICANCE: The findings from this GxE model will provide mechanistic insights into the causes of NDDs; they may inform practice guidelines so as to reduce this environmental exposure; and may suggest interventions like probiotics for those at risk in order to overcome altered gut microbiome composition and restore hippocampal neurogenesis defects.

Early-Life Antibiotics and Childhood Obesity: Yeast Probiotics as a Strategy to Modulate Gut Microbiota.

This study aimed to review the existing literature to investigate the potential link between early-life antibiotic use and being overweight or obese in children. PubMed, Web of Science, Embase, Google Scholar, and Cochrane Library were searched to identify studies published until August 2021 that assessed the relationship between early-childhood antibiotic use and measures of body mass index. The studies included children aged 0-18 years. Only cohort studies were taken into consideration. Studies published in languages other than English were excluded. Antibiotic usage in early life may increase the risk of obesity in children and the addition of yeast probiotics, such as Saccharomyces boulardii CNCM I 745, to antibiotic prescription can serve as a potential option to mitigate this risk.

Early life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis

Liver-resident natural killer cells, a unique lymphocyte subset in liver, develop locally and play multifaceted immunological roles. However, the mechanisms for the maintenance of liver-resident natural killer cell homeostasis remain unclear. Here we show that early-life antibiotic treatment blunt functional maturation of liver-resident natural killer cells even at adulthood, which is dependent on the durative microbiota dysbiosis. Mechanistically, early-life antibiotic treatment significantly decreases butyrate level in liver, and subsequently led to defective liver-resident natural killer cell maturation in a cell-extrinsic manner. Specifically, loss of butyrate impairs IL-18 production in Kupffer cells and hepatocytes through acting on the receptor GPR109A. Disrupted IL-18/IL-18R signaling in turn suppresses the mitochondrial activity and the functional maturation of liver-resident natural killer cells. Strikingly, dietary supplementation of experimentally or clinically used Clostridium butyricum restores the impaired liver-resident natural killer cell maturation and function induced by early-life antibiotic treatment. Our findings collectively unmask a regulatory network of gut-liver axis, highlighting the importance of the early-life microbiota in the development of tissue-resident immune cells.

Associations of intrapartum antibiotics and growth, atopy, gastrointestinal and sleep outcomes at one year of age.

Studies investigating neonatal outcomes following intrapartum antibiotic exposure show conflicting results. Data were collected prospectively in pregnancy to 1-year-of-age, from 212 mother-infant pairs. Adjusted multivariable regression models estimated relationships following exposure to intrapartum antibiotics among vaginally-born, full-term infants and outcomes related to growth, atopic disease, gastrointestinal symptoms, and sleep at 1-year. Intrapartum antibiotic exposure (n = 40) was not associated with mass, ponderal index, BMI z-score (1- year), lean mass index (5-months) or height. Antibiotic exposure in labour ≥4-h was associated with increase in fat mass index at 5-months (β 0.42 [95% CI: 0.03, 0.80], p = 0.03). Intrapartum antibiotic was associated with atopy in the first year (OR: 2.93 [95% CI: 1.34, 6.43], p = 0.007). Antibiotic exposure during intrapartum or day 1-7 was associated with newborn fungal infection requiring antifungal therapy (OR 3.04 [95% CI: 1.14, 8.10], p = 0.026), and number of fungal infections (IRR: 2.90 [95% CI: 1.02, 8.27], p = 0.046). Intrapartum and early life exposure to antibiotics were independently associated with measures of growth, atopy, and fungal infections suggesting that intrapartum and early neonatal antibiotics be used prudently following careful risk-benefit analysis. This prospective study: Shows a shift in fat mass index at 5 months associated with antibiotic administration ≥4 h in labour; an earlier age than previously reported; Shows atopy reported less frequently among those not exposed to intrapartum antibiotics; Supports earlier research of increased likelihood of fungal infection following exposure to intrapartum or early-life antibiotics; Adds to growing evidence that antibiotics used intrapartum and in early neonatal periods influence longer-term outcomes for infants. Suggests that use of intrapartum and early neonatal antibiotics should be used prudently after careful consideration of risk and benefit.

Early-Life Antibiotic Exposure and Childhood Asthma Trajectories: A National Population-Based Birth Cohort

Early-life antibiotic exposure is common and impacts the development of the child's microbiome and immune system. Information on the impacts of early-life antibiotics exposure on childhood asthma is lacking. This study examined associations between early-life (0-24 months) antibiotics exposure with childhood (6-15 years) asthma trajectories through the Australian Longitudinal Study of Australian Children (LSAC) and their linked data from the Pharmaceutical Benefits Scheme. Asthma phenotypes were derived by group-based trajectory modeling. Of 5107 LSAC participants, 4318 were included in the final analyses (84.6% retention). Four asthma phenotypes were identified: Always-low-risk (79.0%), early-resolving asthma (7.1%), early-persistent asthma (7.9%), and late-onset asthma (6.0%). Any early-life antibiotic exposure increased risk 2.3-fold (95% CI: 1.47-3.67; p < 0.001) for early-persistent asthma among all children. In subgroup analyses, early-persistent asthma risk increased by 2.7-fold with any second-generation cephalosporin exposure, and by 2-fold with any β-lactam other than cephalosporin or macrolide exposure. We concluded that early-life antibiotic exposure is associated with an increased risk of early-persistent childhood asthma. This reinforces scrutiny of early-life antibiotic use, particularly for common viral infections where no antibiotics are required.

DOP20 The impact of early life antibiotics on the occurrence of paediatric inflammatory bowel disease - a nationwide study from 1995 – 2018

Abstract Background Early–life antibiotic exposure has been associated with a decreased richness of the microbiome, which is associated with the development of inflammatory bowel disease (IBD). The aim of this study was to assess the risk of developing paediatric-onset IBD (pIBD) after being exposed to systemic antibiotics during the first five years of life. Methods We identified all patients &amp;lt; 18 years old diagnosed with pIBD in Denmark between 1995-2018 in the National Patient Registry. Data on antibiotic prescriptions during first five years of life were retrieved from the National Prescription Register. PIBD patients were matched with up to ten healthy controls. Risk estimates were presented by Hazard ratios (HR). Results We identified 1,808 patients with pIBD (989 Crohn’s disease [CD]/819 ulcerative colitis [UC]) and 17,234 matched controls. An increased risk of developing pIBD was associated with prescription of antibiotics during first five years (HR = 1.32 [95%CI: 1.2-1.5], p= &amp;lt;0.0001), and risk was further increased if the patient had ≥ 4 antibiotic prescriptions compared to no antibiotic prescription (HR = 1.43 [95%CI: 1.2-1.6], p= &amp;lt;0.0001). Prescription of broad-spectrum antibiotics increased the risk of pIBD compared to prescription of only narrow-spectrum antibiotics (HR: 1.19, [95%CI 1.0-1.4], p=0.04). When stratified by IBD subtypes, only CD was significantly associated with exposure to antibiotics (HR = 1.43 [95%CI: 1.2-1.7], p=0.0003). Conclusion In this nationwide registry-based study, we found that antibiotic exposure during first five years of life, was associated with an increased risk of pIBD. Repeated antibiotic exposures increased risk estimates.

The impact of early-life antibiotics and probiotics on gut microbial ecology and infant health outcomes: a Pregnancy and Birth Cohort in Northwest China (PBCC) study protocol

BackgroundUnreasonable use of antibiotics and probiotics can alter the gut ecology, leading to antibiotic resistance and suboptimal health outcomes during early life. Our study aims are to clarify the association among antibiotic and probiotic exposure in early life, the microecology of the gut microbiota, and the development of antibiotic resistance; to investigate the long-term impact of antibiotics and probiotics on the health outcomes of infants and young children; and to provide a theoretical basis for the rational use of antibiotics and probiotics from a life course perspective.MethodsThe study is a prospective, longitudinal birth cohort study conducted in Shaanxi Province, China from 2018 to 2024. A total of 3,000 eligible mother–child pairs will be enrolled from rural, suburban, and urban areas. The recruitment of the participants begins at pregnancy, and the newborns will be followed up for 2 years at successive timepoints: within 3 days after birth, 42 days after birth, and at 3, 6, 12, 18, and 24 months of age. Sociodemographic data, environmental exposures, dietary patterns, psychological conditions, and medical and drug histories are collected. Cognitive and behavioural development among infants and young children and questionnaires on antibiotic knowledge and behaviour among caregivers will be collected at 12 and 24 months of age. The faecal samples are collected and analysed by 16S rRNA high-throughput sequencing and quantitative PCR (qPCR) for antibiotic resistance genes.DiscussionThe findings will inform antibiotic and probiotic use for pregnant women and infants and contribute to establishing rational use strategies of antibiotics and probiotics for paediatricians, health practitioners, and drug administration policy-makers.Trial registrationThe study was registered on the Chinese Clinical Trial Registry (ChiCTR) platform, http://www.chictr.org.cn (Record ID: ChiCTR2100047531, June 20, 2021).

Association between early life antibiotic exposure and development of early childhood atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease commonly onset during infancy. We examine the association between pre-and postnatal antibiotic exposure and the development of AD. A retrospective, observational study analyzed 4106 infants at the University of Florida from June 2011 to April 2017. Antibiotic exposure during the first year of life was associated with a lower risk of AD. The association was strongest for exposure during the first month of life. There were no significant differences in the rates of AD in infants with or without exposure to antibiotics in months 2 through 12, when examined by month. Antibiotic exposure during week 2 of life was associated with lower risk of AD, with weeks 1, 3, and 4 demonstrating a similar trend. Retrospective data collection from a single center, use of electronic medical record, patient compliance with prescribed medication, and variable follow-up. Early life exposures, such as antibiotics, may lead to long-term changes in immunity. Murine models of atopic dermatitis demonstrate a "critical window" for the development of immune tolerance to cutaneous microbes. Our findings suggest that there may also be a "critical window" for immune tolerance in human infants, influenced by antibiotic exposure.

Meta-analysis of early-life antibiotic use and allergic rhinitis.

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 <0.001). In Asia, Europe, and the USA, the incidence of allergic rhinitis in the antibiotic group was higher than that in the no medication group (Asia: ES = 3.68, 95% CI: 3.38-4.01; Europe: ES = 3.20, 95% CI: 3.00-3.42; USA: ES = 3.68, 95% CI: 2.74-4.95). Compared with the no medication group, children who received antibiotics in the first 1 week of life (ES = 5.75, 95% CI: 2.18-15.18), first 1 year of life (ES = 3.37, 95% CI: 3.20-3.55; I 2 = 64.2%, P heterogeneity = 0.001), or first 3 years of life (ES = 5.21, 95% CI: 2.42-11.19) had a higher incidence of allergic rhinitis. No individual study influenced the estimates of the meta-analysis. The funnel plot showed moderate symmetry and low publication bias. In conclusion, the use of antibiotics in early life was associated with allergic rhinitis. Still, most included studies analyzed antibiotic exposure as a dichotomous variable, without information on the type and dosage of antibiotics.

Antibiotics in Early Life: Dysbiosis and Damage Done

Antibiotic are the most common type of medication prescribed to children, including infants, in western world. Antibiotics alter the gut microbial composition. Since the gut microbiota plays crucial role in immunity, metabolism and endocrinology the effects of antibiotics on the microbiota may lead to further health complications. Antibiotic in childhood have been linked with disease including asthma, juvenile, arthritis, type 1diabets, chronic disease and mental illness. In COVID-19 probiotics plays a therapeutic role for GI, IBD, colitis, and even in viral infection. So, we assume that the inclusion of studies to investigate gut microbiome and subsequent therapies such as probiotic might help decrease the inflammatory response of viral pathogenesis and respiratory symptoms by strengthening the host immune system, amelioration of gut microbiome, and improvement of gut barrier function. Focused on four types of dysbiosis loss of keystone taxa, loss of diversity. Establishment of large and diverse baseline healthy infant microbiome development is essential to advancing diagnosis interpretation and eventual treatment pediatric dysbiosis. In this review we present an overview of effects of antibiotics on microbiome in children and correlate them to long lasting complications. Objectives: • To review on antibiotics are alter the gut microbial composition in children, adult. • To review on gut microbiota plays crucial roles in immunity, metabolism and endocrinology, the effects of antibiotics on microbiota may lead to further health..

Early Life Antibiotic Prescription for Upper Respiratory Tract Infection Is Associated With Higher Antibiotic Use in Childhood.

Antibiotic prescription for uncomplicated upper respiratory tract infection (URTI) in children is not recommended but remains common. The primary objective was to evaluate the relationship between antibiotic prescription for URTI prior to age 2 and antibiotic prescription for URTI after age 2. It was hypothesized that antibiotic prescription for URTI in early childhood may increase the risk of antibiotic use for subsequent URTIs. The secondary objective was to investigate whether this relationship was different for acute otitis media (AOM), for which antibiotics may be indicated. A prospective cohort study was conducted between December 2008 and March 2016 at 9 primary care practices in Toronto, Canada. Healthy children aged 0-5 years that met TARGet Kids! cohort eligibility criteria were included if they had at least one sick visit prior to age 2 and least one sick visit after age 2. Generalized Estimating Equation (GEE) models were used to evaluate this relationship while considering within-subject correlation. Of 2380 participants followed for a mean duration of 4.6 years, children who received an antibiotic prescription for URTI prior to age 2 had higher odds of receiving an antibiotic prescription for URTI in later childhood (adjusted odds ratio: 1.39; 95% confidence interval: 1.19 to 1.63; P < .001). This relationship did not appear to be different for AOM compared to non-AOM URTI. Antibiotic prescription for URTI before age 2 was associated with antibiotic prescription for URTI in later childhood. Reducing early life antibiotic prescription for URTI may be associated with reduction in antibiotic prescription for subsequent URTIs.

Neonatal antibiotics have long term sex-dependent effects on the enteric nervous system.

Infants and young children receive the highest exposures to antibiotics globally. Although there is building evidence that early life exposure to antibiotics increases susceptibility to various diseases including gut disorders later in life, the lasting impact of early life antibiotics on the physiology of the gut and its enteric nervous system (ENS) remains unclear. We treated neonatal mice with the antibiotic vancomycin during their first 10 postnatal days, then examined potential lasting effects of the antibiotic treatment on their colons during young adulthood (6weeks old). We found that neonatal vancomycin treatment disrupted the gut functions of young adult female and male mice differently. Antibiotic-exposed females had significantly longer whole gut transit while antibiotic-treated males had significantly lower faecal weights compared to controls. Both male and female antibiotic-treated mice had greater percentages of faecal water content. Neonatal vancomycin treatment also had sexually dimorphic impacts on the neurochemistry and Ca2+ activity of young adult myenteric and submucosal neurons. Myenteric neurons of male mice were more disrupted than those of females, while opposing changes in submucosal neurons were seen in each sex. Neonatal vancomycin also induced sustained changes in colonic microbiota and lasting depletion of mucosal serotonin (5-HT) levels. Antibiotic impacts on microbiota and mucosal 5-HT were not sex-dependent, but we propose that the responses of the host to these changes are sex-specific. This first demonstration of long-term impacts of neonatal antibiotics on the ENS, gut microbiota and mucosal 5-HT has important implications for gut function and other physiological systems of the host. KEY POINTS: Early life exposure to antibiotics can increase susceptibility to diseases including functional gastrointestinal (GI) disorders later in life. Yet, the lasting impact of this common therapy on the gut and its enteric nervous system (ENS) remains unclear. We investigated the long-term impact of neonatal antibiotic treatment by treating mice with the antibiotic vancomycin during their neonatal period, then examining their colons during young adulthood. Adolescent female mice given neonatal vancomycin treatment had significantly longer whole gut transit times, while adolescent male and female mice treated with neonatal antibiotics had significantly wetter stools. Effects of neonatal vancomycin treatment on the neurochemistry and Ca2+ activity of myenteric and submucosal neurons were sexually dimorphic. Neonatal vancomycin also had lasting effects on the colonic microbiome and mucosal serotonin biosynthesis that were not sex-dependent. Different male and female responses to antibiotic-induced disruptions of the ENS, microbiota and mucosal serotonin biosynthesis can lead to sex-specific impacts on gut function.

Associations between pre- and postnatal antibiotic exposures and early allergic outcomes: A population-based birth cohort study.

BackgroundEarly life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre‐ and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months.MethodsWe included 1387 mother–child dyads from the prospective, population‐based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web‐based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician‐diagnosed asthma; parents (n = 1025) reported physician‐diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions.ResultsPrenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01–3.26) but not in the adjusted analyses (aOR 1.58, 0.82–3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95–2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47–3.11), asthma (aOR 2.35, 1.32–4.19), and eczema (aOR 1.49, 1.07–2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25–0.83) but not with food allergy nor sensitization to inhalants.ConclusionPre‐ and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.

Neonatal Early Onset Sepsis (EOS) Calculator plus Universal Serial Physical Examination (SPE): A Prospective Two-Step Implementation of a Neonatal EOS Prevention Protocol for Reduction of Sepsis Workup and Antibiotic Treatment.

Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice is found in Neonatal Units, with a large number of non-infected newborns evaluated and treated for EOS. Broad spectrum antibiotics in early life may induce different short- and long-term adverse effects, longer hospitalization, and early mother-child separation. In this single-center prospective study, a total of 3002 neonates born in three periods between 2016 and 2020 were studied, and three different workup algorithms were compared: the first one was based on the categorical risk assessment; the second one was based on a Serial Physical Examination (SPE) strategy for infants with EOS risk factors; the third one associated an informatic tool (Neonatal EOS calculator) with a universal extension of the SPE strategy. The main objective of this study was to reduce the number of neonatal sepsis workups and the rate of antibiotic administration and favor rooming-in and mother–infant bonding without increasing the risk of sepsis and mortality. The combined strategy of universal SPE with the EOS Calculator showed a significant reduction of laboratory tests (from 33% to 6.6%; p < 0.01) and antibiotic treatments (from 8.5% to 1.4%; p < 0.01) in term and near-term newborns. EOS and mortality did not change significantly during the study period.

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life.

The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health effects. Here, we investigated whether AB-induced changes in the neonatal gut persisted up to adulthood and whether early life AB had additional long-term consequences for gut functioning. Mice received AB orally from postnatal day 10 to 20. Intestinal morphology, permeability, and gene and protein expression at 8 weeks were analyzed. Our data showed that the majority of the early life AB-induced gut effects did not persist into adulthood, yet early life AB did impact later life gut functioning. Specifically, the proximal small intestine (SI) of adult mice treated with AB in early life was characterized by hyperproliferative crypts, increased number of Paneth cells, and alterations in enteroendocrine cell-specific gene expression profiles. The distal SI of adult mice displayed a reduced expression of antibacterial defense markers. Together, our results suggest that early life AB leads to structural and physiological changes in the adult gut, which may contribute to disease development when homeostatic conditions are under challenge.