Neonatal Gut Microbiota Research Articles

Landscapes of maternal and neonatal gut microbiome and plasma metabolome signatures and their interaction in gestational diabetes mellitus

BackgroundGestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and foetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the foetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures. MethodsThis study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycaemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyse the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics. ResultsDistinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycaemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between Qipengyuania and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycaemic mothers and newborns, but these correlations were disrupted in the GDM group. ConclusionOur findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.

Experimental models of antibiotic exposure and atopic disease.

In addition to numerous clinical studies, research using experimental models have contributed extensive evidence to the link between antibiotic exposure and atopic disease. A number of mouse models of allergy have been developed and used to uncover the specific effects of various microbiota members and perturbations on allergy development. Studies in mice that lack microbes entirely have also demonstrated the various components of the immune system that require microbial exposure. The importance of the early-life period and the mechanisms by which atopy "protective" species identified in human cohorts promote immune development have been elucidated in mice. Finally, non-animal models involving human-derived cells shed light on specific effects of bacteria on human epithelial and immune responses. When considered alongside clinical cohort studies, experimental model systems have provided crucial evidence for the link between the neonatal gut microbiota and allergic disease, immensely supporting the stewardship of antibiotic administration in infants. The following review aims to describe the range of experimental models used for studying factors that affect the relationship between the gut microbiota and allergic disease and summarize key findings that have come from research in animal and in vitro models.

C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity

Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.

Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting.

The gut microbiota, comprising billions of microorganisms, plays a pivotal role in health and disease. This study aims to investigate the effect of sepsis on gut microbiome of neonates admitted to the Neonatal Intensive Care Unit. A prospective cohort study was carried out in the NICU of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Preterm neonates with birth weight < 1500g and gestational age < 37 weeks were recruited, excluding those with congenital gastrointestinal anomalies, necrotizing enterocolitis, or blood culture-negative infections. The study population was divided into three groups: healthy neonates (Group A), neonates with drug-sensitive GNB sepsis (Group B), and neonates with pan drug-resistant GNB sepsis (Group C). Stool samples were collected aseptically, snapped in liquid nitrogen, and stored at -80⁰C for extraction of DNA and microbiome analysis. The gut microbiota of healthy neonates (Group A) was dominated by Proteobacteria (24.04%), Actinobacteria (27.13%), Firmicutes (12.74%), and Bacteroidetes (3%). Predominant genera included Bifidobacterium (55.17%), Enterobacter (12.55%), Enterococcus (50.69%), Streptococcus (7.92%), and Bacteroides (3.58%).Groups B and C, the microbiota exhibited higher Proteobacteria abundance (57.16% and 66.58%, respectively) and reduced diversity of beneficial bacteria. Notably, the presence of sepsis was associated with an increase in pathogenic bacteria and a decrease in beneficial commensal bacteria. Neonates with sepsis exhibited significant gut microbiome dysbiosis, characterized by increased Proteobacteria and reduced beneficial bacteria diversity. These findings highlight the potential of microbiome profiling as a diagnostic tool and underscore the importance of gut microbiota modulation in managing neonatal sepsis.

Primary succession of Bifidobacteria drives pathogen resistance in neonatal microbiota assembly

Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life.

Extracting and Characterizing Lactic Acid Bacteria from Human Milk

The greatest diet for babies is breast milk since it meets all of their nutritional needs and promotes healthy growth and development. Human milk contains thousands of different bacteria, the most prevalent ones being lactobacillus and Bifido bacterium. Since the use of probiotics is growing daily, it's important to comprehend their properties and health advantages. The combination of protein, fats, carbs, lipids, minerals, and vitamins found in breast milk helps to nourish an infant's body. Additionally, the bacteria in breast milk offer defense against infections. We will learn about lactic acid bacteria from this study so that we can commercially make probiotics from strains of these bacteria without utilizing lactose, as certain people are lactose intolerant and do not consume any lactose-containing products. The purpose of this article is to identify and isolate lactic acid bacteria while also discussing the advantages of probiotics for health. To understand the role lactic acid bacteria (LAB) from human milk play in the development and health of neonates, LAB must be extracted and identified. This study's objective was to identify, characterize, and segregate LAB strains from human milk samples obtained from nursing mothers in good health. The first isolation was carried out using selective medium, and then morphological, biochemical, and molecular characterization were performed. Through 16S rRNA gene sequencing, the isolates were identified. All things considered, the development of the neonatal gut microbiota and the overall health of infants depend on lactic acid bacteria (LAB). This review's objective is to gather the most recent data on the identification and isolation of LAB from human milk, with an emphasis on the techniques employed, the types of LAB discovered, and any potential health risks. Human milk is an essential source of beneficial bacteria, including several species of lactobacilli (LAB), due to its complex and dynamic nature. Our ability to isolate and accurately identify these germs has improved due to technological advancements in the molecular and microbiological sciences. This paper provides an extensive overview of the methods utilized to extract LAB from human milk, the genera and species that are commonly detected, and the implications of these findings for the nutrition and health of neonates.

Effect of β-lactam antibiotics on the gut microbiota of term neonates

β-Lactam antibiotics are a class of antibiotics commonly used to treat bacterial infections. However, the effects of β-lactam antibiotics on term neonatal intestinal flora have not been fully elucidated. Hospitalized full-term newborns receiving β-lactam antibiotics formed the antibiotic group (n = 67), while those without antibiotic treatment comprised the non-antibiotic group (n = 47). A healthy group included healthy full-term newborns (n = 16). Stool samples were collected for 16 S rDNA sequencing to analyze gut microbiota variations. Further investigation was carried out within the β-lactam antibiotic group, exploring the effects of antibiotic use on the newborns’ gut microbiota in relation to the duration and type of antibiotic administration, delivery method, and feeding practices. The antibiotic group exhibited significant difference of microbial community composition compared to the other groups. Genera like Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas were enriched, while Escherichia-Shigella, Clostridium sensu stricto 1, Bifidobacterium, and Parabacteroides were reduced. Klebsiella negatively correlated with Escherichia-Shigella, positively with Enterobacter, while Escherichia-Shigella negatively correlated with Enterococcus and Streptococcus. Regardless of neonatal age, β-lactam antibiotics induced an elevated abundance of Klebsiella and Enterococcus. The impact on gut microbiota varied with the duration and type of antibiotic (cefotaxime or ampicillin/sulbactam). Compared to vaginal delivery, cesarean delivery after β-lactam treatment heightened the abundance of Klebsiella, Enterobacteriaceae_Unclassified, Lactobacillales_Unclassified, and Pectobacterium. Feeding patterns minimally influenced β-lactam-induced alterations. In conclusion, β-lactam antibiotic treatment for neonatal pneumonia and sepsis markedly disrupted intestinal microbiota, favoring Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas. The impact of β-lactam varied by duration, type, and delivery method, emphasizing heightened disruptions post-cesarean delivery.

What Happens in the Gut during the Formation of Neonatal Jaundice-Underhand Manipulation of Gut Microbiota?

Jaundice is a symptom of high blood bilirubin levels affecting about 80% of neonates. In neonates fed with breast milk, jaundice is particularly prevalent and severe, which is likely multifactorial. With the development of genomics and metagenomics, a deeper understanding of the neonatal gut microbiota has been achieved. We find there are accumulating evidence to indicate the importance of the gut microbiota in the mechanism of jaundice. In this paper, we present new comprehensive insight into the relationship between the microbiota and jaundice. In the new perspective, the gut is a crucial crossroad of bilirubin excretion, and bacteria colonizing the gut could play different roles in the excretion of bilirubin, including Escherichia coli as the main traffic jam causers, some Clostridium and Bacteroides strains as the traffic police, and most probiotic Bifidobacterium and Lactobacillus strains as bystanders with no effect or only a secondary indirect effect on the metabolism of bilirubin. This insight could explain why breast milk jaundice causes a longer duration of blood bilirubin and why most probiotics have limited effects on neonatal jaundice. With the encouragement of breastmilk feeding, our perspective could guide the development of new therapy methods to prevent this side effect of breastfeeding.

The Impact of Gestational Diabetes Mellitus (GDM) on the Development and Composition of the Neonatal Gut Microbiota: A Systematic Review.

Gestational diabetes mellitus (GDM) is an important health issue, as it is connected with adverse effects to the mother as well as the fetus. A factor of essence for the pathology of this disorder is the gut microbiota, which seems to have an impact on the development and course of GDM. The role of the gut microbiota on maternal reproductive health and all the changes that happen during pregnancy as well as during the neonatal period is of high interest. The correct establishment and maturation of the gut microbiota is of high importance for the development of basic biological systems. The aim of this study is to provide a systematic review of the literature on the effect of GDM on the gut microbiota of neonates, as well as possible links to morbidity and mortality of neonates born to mothers with GDM. Systematic research took place in databases including PubMed and Scopus until June 2024. Data that involved demographics, methodology, and changes to the microbiota were derived and divided based on patients with exposure to or with GDM. The research conducted on online databases revealed 316 studies, of which only 16 met all the criteria and were included in this review. Research from the studies showed great heterogeneity and varying findings at the level of changes in α and β diversity and enrichment or depletion in phylum, gene, species, and operational taxonomic units in the neonatal gut microbiota of infants born to mothers with GDM. The ways in which the microbiota of neonates and infants are altered due to GDM remain largely unclear and require further investigation. Future studies are needed to explore and clarify these mechanisms.

2′-Fucosyllactose promotes the enrichment of Akkermansia muciniphila and the production of short-chain fatty acids in vitro and in vivo

2′-Fucosyllactose (2′-FL), a prebiotic in human milk, has been shown to enhance the growth of Akkermansia muciniphila (A. muciniphila). Our objective is to explore the impacts of 2′-FL on the growth of A. muciniphila and the production of short-chain fatty acids (SCFAs), and its role in improving gut microbiota. In this study, our results demonstrated that 2′-FL could be used by A. muciniphila for growth, and it was metabolized into SCFAs, especially butyrate and propionate. Furthermore, the supplementation with 2′-FL led to a reduction in the Firmicutes/Bacteroidetes (F/B) ratio as well as a notable enrichment in the abundance of A. muciniphila and Muribaculaceae in mice feces. Additionally, the supplementation of 2′-FL also significantly elevated the content of SCFAs in vivo. Importantly, our findings suggested that 2′-FL might function as a prebiotic, promoting gut health by stimulating the enrichment of A. muciniphila, increasing the production of SCFAs and improving the microbiota in the gut, thereby enhancing intestinal barrier integrity, reducing intestinal inflammation and regulating immune response. Our research contributes to providing a strategy for addressing neonatal gut microbiota dysbiosis or enteritis.

The Association of Neonatal Gut Microbiota Community State Types with Birth Weight.

while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota's composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants.

Comparative Effect of Breast Milk and Infant Formulae on Neonatal Gut Microbiome within Katsina Metropolis

Study’s Novelty/ Excerpt This study explored the impact of breast milk versus infant formula on the gut microbiota of neonates in Katsina metropolis, revealing significant differences in bacterial composition and fecal pH between the two groups. Exclusively breastfed infants exhibited a lower fecal pH (5.09±0.1) and higher weights, with similar levels of Escherichia spp. and Bifidobacterium spp., while formula-fed infants showed a higher fecal pH (5.9±0.1) and differences in Escherichia spp. loads. Despite advances in infant formula enrichment, the study underscores the distinct influence of breast milk on neonatal gut microbiota composition and health. Full Abstract Numerous studies conducted in recent years have highlighted the intricate nature of the neonatal gut microbiome, influenced by various intrinsic and extrinsic factors. One significant factor in this regard is the type of feeding, which has a substantial impact on the development of intestinal microbiota in early infancy. This study aimed to compare the effects of breast milk and infant formulae on the gut microbiota of newborns in Katsina metropolis. Faecal samples were obtained from 46 neonates (33 exclusively breastfed, 10 formula-fed, and 3 mix-fed) and analyzed using a culture-dependent method. Colony enumerations and pH measurements were conducted for comparison between the groups. The mean weight of the participants was 2.88±0.1 kg, with exclusively breastfed infants (BFI) weighing significantly more (p = 0.03) than formula-fed infants (FFI). The bacteria selected for analysis (Bifidobacterium spp., Staphylococcus spp., Escherichia spp., and Lactobacillus spp.) were present in all feeding groups. Among BFI, similar levels of Escherichia spp. and Bifidobacterium spp. (61.17 CFU/g and 61.38 CFU/g respectively) were observed. Staphylococcus spp. constituted the majority of the bacterial load (32%) in both BFI and FFI groups. Apart from Escherichia spp. (p = 0.01), no significant differences were noted in the levels of all cultured bacteria across the feeding groups. The disparity in Escherichia spp. load was evident between BFI and MFI (p = 0.01), as well as FFI and MFI (p = 0.02) only. There was no overall significant correlation between bacterial load and mode of delivery within the feeding groups (p = 0.6). The average faecal pH of breastfed infants (5.09±01) was significantly lower (p = &lt;0.001) compared to the formula-fed group (5.9±0.1). Despite advancements in enriching infant formulae with probiotics and other bifidogenic substances, subtle differences in fecal bacterial load compared to breast milk persist, highlighting the significant influence of both feeding methods on the composition and functionality of the neonatal gut microbiome

Hydrogen peroxide in breast milk is crucial for gut microbiota formation and myelin development in neonatal mice

ABSTRACT Early life environment influences mammalian brain development, a growing area of research within the Developmental Origins of Health and Disease framework, necessitating a deeper understanding of early life factors on children’s brain development. This study introduces a mouse model, LAO1 knockout mice, to investigate the relationship between breast milk, the gut microbiome, and brain development. The results reveal that breast milk‘s reactive oxygen species (ROS) are vital in shaping the neonatal gut microbiota. Decreased hydrogen peroxide (H2O2) levels in milk disrupt the gut microbiome and lead to abnormal metabolite production, including D-glucaric acid. This metabolite inhibits hippocampal myelin formation during infancy, potentially contributing to behavioral abnormalities observed in adulthood. These findings suggest that H2O2 in breast milk is crucial for normal gut microbiota formation and brain development, with implications for understanding and potentially treating neurodevelopmental disorders in humans.

State of the Art: Intrapartum Antibiotics in Cesarean Section—The Infant Microbiota and Allergic Diseases

(Acta Obstet Gynecol Scand. 2023;102:811–820) Recent changes in guidelines for administering maternal antibiotics for cesarean deliveries (CD) have increased neonatal exposure to antibiotics. Potential long-term effects of this exposure are relatively unknown; recent evidence in other fields has indicated a long-lasting impact of antibiotic exposure on gut microbiota composition, which raises concerns about the effects of antibiotics on the fragile and new gut microbiota of neonates around the time of birth. This review assessed the current guidelines and applications for CD antibiotics, as well as discussed the importance of neonatal intestinal microbiota and the potential consequences of antibiotic prophylaxis in the development of the neonatal immune system and allergic disease.

Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks.

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.

Origin of the neonatal gut microbiota and probiotic intervention: a randomized controlled trial.

This study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester. Samples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota. We found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

Association between labor epidural analgesia and gut microbiota: A prospective cohort study

BackgroundLabor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns. MethodsIn this prospective cohort study, parturients aged 25–35 years with a gestational age of 37–42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models. ResultsWe showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and β-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (β = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (β = −449.36, adjusted P = 0.015), P. aeruginosa (β = −192.55, adjusted P = 0.008), or S. maltophilia (β = −142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (β = −2702.77, adjusted P = 0.003) in neonates. ConclusionLEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

Wide use of broad-spectrum antibiotics in very low birth weight infants with spontaneous focal intestinal perforation—is it really justified?

PurposeVery low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship.MethodsData on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed.ResultsIn the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria (n = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently (n = 96 (78.0%)).ConclusionThe use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs).

Intestinal microbiota modulates neuroinflammatory response and brain injury after neonatal hypoxia-ischemia

ABSTRACT Premature infants lack a normal intestinal microbial community and also at risk of perinatal hypoxic-ischemic (HI) brain injury, which is considered to be one of the major factors for motor, sensory, and cognitive deficits. We hypothesized that neonatal gut microbiota composition modulated the immune reaction and severity of neonatal H-I brain injury. Neonatal C57BL/6J mouse pups were exposed to H-I protocol consisting of permanent left carotid artery ligation, followed by 8% hypoxia for 60 min. Microbial manipulation groups included 1) antibiotic treatment, E18 (maternal) to P5; 2) antibiotic treatment E18 to P5 + E. coli gavage; 3) antibiotic treatment E18 to P5 + B. infantis gavage; and 4) saline to pups with dams getting fresh water. The extent of brain injury and recovery was measured on MRI. Edematous injury volume was significantly higher in E. coli group than that in B. infantis group and in fresh water group. Gene expression in brains of pro-inflammatory cytokines (IL1β, IL6, IL2, TNF-α and toll-like receptors 2–6) were elevated to a greater extent in the E. coli group at P10, no injury, and at P13, 72 hours after H-I relative to sham control and B. infantis groups. Significant effects of microbiome and brain injury and interaction of these factors were found in abundance of major phyla. The neuroinflammatory response and brain injury after neonatal hypoxia-ischemia are affected by intestinal microbiota, providing opportunities for therapeutic intervention through targeting the early colonization and development of the gut microbiota.

Gut Microbiota and Symptom Expression and Severity in Neonatal Abstinence Syndrome.

Problem: Neonatal abstinence syndrome (NAS) affecting neonates with fetal exposure to opioids, is defined by expression and severity of symptoms. The pathophysiology behind symptoms variability is lacking. The study aims were to examine (a) differences in gut microbiota of neonates with and without NAS, (b) the relationships between gut microbiota and symptom expression and NAS severity, and (c) the changes in the neonate gut microbiota diversity during the course of NAS treatment. Methods: A cross-sectional observational design was used to examine differences in microbiota and a longitudinal, repeated measures approach was used to determine relationships between gut microbiota and NAS symptoms. Symptom data were collected using the Finnegan Neonatal Abstinence Scoring Tool and the Neonatal Pain Agitation and Sedation Scale. Stool samples were collected for microbiome analyses with 16S rRNA microbiome sequencing. Results: Differences in alpha and beta diversity between neonates with and without NAS were seen. Relative abundance results revealed 18 taxa were different in neonates with NAS compared to neonates without NAS. No differences were found in alpha or beta diversity in neonates with NAS between enrollment and hospital discharge. There was increased abundance of Escherichia-Shigella and Bacteriodes genera related to higher symptom scores. Discussion: Differences in alpha and beta diversity between neonates with and without NAS may be due to differences in birth mode and type of feeding. The findings of specific increased bacteria related to increased symptoms in the neonates with NAS may also be influenced by birth mode and type of feeding.