Maternal Antibiotics Research Articles

Time to Positivity of Neonatal Blood Cultures for Early-onset Sepsis

In newborns at risk for early-onset sepsis, empiric antibiotics are often initiated while awaiting the results of blood cultures. The duration of empiric therapy can be guided by the time to positivity (TTP) of blood cultures. The objective of the study was to determine the TTP of neonatal blood cultures for early-onset sepsis and the factors which may impact TTP. Observational study of blood cultures growing pathogenic species obtained within 72 hours of birth from infants born at 23-42 weeks gestation, at 19 hospitals in Northern California, Boston, and Philadelphia. TTP was defined as the time from blood culture collection to the time organism growth was reported by the microbiology laboratory. A total of 594 blood cultures growing pathogenic bacteria were identified. Group B Streptococcus and Escherichia coli accounted for 74% of blood culture isolates. Median TTP was 21.0 hours (interquartile range, 17.1-25.3 hours). Blood cultures were identified as positive by 24 hours after they were obtained in 68% of cases; by 36 hours in 94% of cases; and by 48 hours in 97% of cases. Neither the administration of maternal intrapartum antibiotic prophylaxis, gestational age <35 weeks, nor blood culture system impacted median TTP. Pathogens are isolated by 36 hours after blood culture collection in 94% of neonatal early blood cultures, regardless of maternal antibiotic administration. TTP information can inform decisions regarding the duration of empiric neonatal antibiotic therapies.

The effect of maternal antibiotic use in sows on intestinal development in offspring.

The objective of this study is to investigate the effect of a maternal antibiotic administration during the last week of gestation on the early life intestinal development in neonatal piglets. Colonization of the gut with bacteria starts during birth and plays a major role in the intestinal and immunological development of the intestine. We demonstrate that maternal interventions induced changes in the sows (n = 6 to 8 per treatment) fecal microbiota diversity around birth (P < 0.001, day 1). Whole-genome microarray analysis in small intestinal samples of 1-d old piglets (n = 6 to 8 per treatment) showed significantly expressed genes (Padj < 0.05) which were involved in processes of tight junction formation and immunoglobulin production. Furthermore, when performing morphometry analysis, the number of goblet cells in jejunum was significantly (P < 0.001) lower in piglets from amoxicillin administered sows compared with the respective control piglets. Both significantly expressed genes (Padj < 0.05) and significant morphometry data (jejunum P < 0.05 and ileum P < 0.01) indicate that the crypts of piglets from amoxicillin administered sows deepen around weaning (day 26) as an effect of the amoxicillin administration in sows. The latter might imply that the intestinal development of piglets was delayed by maternal antibiotic administration. Taken together, these results show that maternally oral antibiotic administration changes in early life can affect intestinal development of the offspring piglets for a period of at least 5 wk after the maternal antibiotic administration was finished. These results show that modulation of the neonatal intestine is possible by maternal interventions.

Maternal antepartum antibiotic administration and patterns of bacterial resistance in early preterm neonates

Objective The objective of this study was to determine the relationship between maternal antepartum antibiotic administration and antibiotic resistance patterns in preterm neonates admitted to the neonatal intensive care unit (NICU). Methods This was a retrospective cohort study of women and their preterm neonates delivered at a single tertiary care center over a 5-year period. Women and neonates were included if they delivered between 23 weeks 0 days and 28 weeks 6 days of gestation and neonates were admitted to the NICU. Subjects were excluded if there was incomplete antibiotic administration data or incomplete laboratory or bacterial culture data for either mothers or neonates. Data collected from maternal and neonatal charts included the type, duration, and total number of antibiotics administered to subjects, neonatal culture results within the first 7 days of life, and bacterial antibiotic resistance information. Women with neonates that cultured positive for bacteria demonstrating antibiotic resistance were compared to those whose neonates did not have antibiotic-resistant bacteria. Results 79 women with 90 neonates met inclusion criteria. Of the 79 women, 71 (89.9%) received at least 1 antibiotic antepartum. 14 neonatal bacterial isolates were resistant to at least 1 antibiotic. Antibiotic-resistant bacteria were present in 11 neonates; 3 neonates had more than 1 resistant bacteria cultured. The most common resistant bacteria cultured were Coagulase-negative Staphylococcus (6/14, 42.9%), S. aureus (3/14, 21.4%), and E. coli (2/14, 14.3%). Enterobacter spp (2) and Klebsiella pneumoniae (1) made up the remainder. Of the 11 neonates with resistant bacteria isolated, 10 of their mothers received antibiotics antepartum. Neonates with antibiotic-resistant bacterial isolates were more likely to be born at lower gestational ages (24.6 vs 25.9 weeks, p = .013) and have lower mean birth weights (679.5 vs 849.3 g, p = .009) than those without resistant bacteria. In 8 of 11 (73%) neonates with resistant bacteria, the mother received an antibiotic to which the bacteria cultured were resistant: 6 coagulase-negative Staphylococcus, 1 MRSA, and 1 S. aureus. Conclusions Although preterm neonates are often treated for presumed sepsis, they infrequently have positive bacterial cultures. In this study, those that had positive bacterial cultures for resistant bacteria were born at earlier gestational ages and had lower birth weights. These bacteria cultured in neonates are likely to be resistant to antibiotics received by mothers in the antepartum period. Careful selection of maternal and neonatal antibiotics in the preterm setting with consideration for local antibiotic resistance patterns is suggested.

Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model

Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases. This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes. Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intraamniotic inoculation with Ureaplasma parvum (107 colony-forming units/mL, n=15), and intraamniotic infection plus azithromycin treatment (12.5 mg/kg twice a day intravenously, n=8) groups. At approximately 135 days' gestation (term=165 days), pulsed and color Doppler ultrasonography was used to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebroplacental ratio, and left and right ventricular cardiac outputs) and cardiac function (ratio of peak early vs late transmitral flow velocity [marker of ventricular function], Tei index [myocardial performance index]). These indices were stratified by amniotic fluid proinflammatory mediator levels and cardiac histology. Umbilical and fetal pulmonary artery vascular impedances were significantly increased in animals from the intraamniotic inoculation with Ureaplasma parvum group (P<.05). Azithromycin treatment restored values to control levels. Amniotic fluid prostaglandin F2 alpha levels were significantly higher in animals with abnormal umbilical artery pulsatility index (>1.1) than in those with normal blood flow (P<.05; Spearman ρ=0.6, P<.05). In the intraamniotic inoculation with Ureaplasma parvum group, left ventricular cardiac output was significantly decreased (P<.001), and more animals had abnormal right-to-left ventricular cardiac output ratios (defined as >1.6, P<.05). Amniotic fluid interleukin-6 concentrations were elevated in cases of abnormal right-to-left ventricular cardiac output ratios compared with those in normal cases (P<.05). Fetal hemodynamic alterations were associated with intraamniotic Ureaplasma infection and ameliorated after maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation and in the evaluation of therapeutic interventions or clinical management of preterm labor.

Antibiotic use during pregnancy increases offspring asthma severity in a dose-dependent manner.

The use of antibiotics during pregnancy is associated with increased allergic asthma risk in the offspring, and given that approximately 25% of pregnant women are prescribed antibiotics, it is important to understand the mechanisms contributing to this phenomenon. Currently, there are no studies that directly test this association experimentally. Our objective was to develop a mouse model in which antibiotic treatment during pregnancy results in increased offspring asthma susceptibility. Pregnant mice were treated daily from gestation day 8-17 with an oral solution of the antibiotic vancomycin, and three concentrations were tested. At weaning, offspring were subjected to an adjuvant-free experimental asthma protocol using ovalbumin as an allergen. The composition of the gut microbiome was determined in mothers and offspring with samples collected from five different time points; short-chain fatty acids were also analyzed in allergic offspring. We found that maternal antibiotic treatment during pregnancy was associated with increased offspring asthma severity in a dose-dependent manner. Furthermore, maternal vancomycin treatment during pregnancy caused marked changes in the gut microbiome composition in both mothers and pups at several different time points. The increased asthma severity and intestinal microbiome changes in pups were also associated with significantly decreased cecal short-chain fatty acid concentrations. Consistent with the "Developmental Origins Hypothesis," our results confirm that exposure to antibiotics during pregnancy shapes the neonatal intestinal environment and increases offspring allergic lung inflammation.

Do children exposed to maternal antibiotics during gestation have increased risk of allergic and autoimmune disease compared with those who were not exposed?

Do children exposed to maternal antibiotics during gestation have increased risk of allergic and autoimmune disease compared with those who were not exposed?

Mouse mothers transfer metabolic mode

Microbiota Obesity and metabolic diseases tend to go together, and humans who become obese are also prone to type 2 diabetes and cardiovascular problems. Starting with the observation that offspring of germ-free mice tended to become obese on high-fat diets, Kimura et al. investigated how the presence of the microbiota might be protective in mice (see the Perspective by Ferguson). Short-chain fatty acids (SCFAs) from the microbiota are known to suppress insulin signaling and reduce fat deposition in adipocytes. Further experiments showed that SCFAs in the bloodstream were able to pass from a non–germ-free mother's gut microbiota across the placenta and into the developing embryos. The authors found that in the embryos, the SCFA propionate mediates not only insulin levels through GPR43 signaling but also sympathetic nervous system development through GPR41 signaling. A high-fiber diet promoted propionate production from the maternal microbiota, and maternal antibiotic treatment resulted in obese-prone offspring. Science , this issue p. [eaaw8429][1]; see also p. [978][2] [1]: /lookup/doi/10.1126/science.aaw8429 [2]: /lookup/doi/10.1126/science.aba7673

Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice

Antibiotics and dietary habits can affect the gut microbial community, thus influencing disease susceptibility. Although the effect of microbiota on the postnatal environment has been well documented, much less is known regarding the impact of gut microbiota at the embryonic stage. Here we show that maternal microbiota shapes the metabolic system of offspring in mice. During pregnancy, short-chain fatty acids produced by the maternal microbiota dictate the differentiation of neural, intestinal, and pancreatic cells through embryonic GPR41 and GPR43. This developmental process helps maintain postnatal energy homeostasis, as evidenced by the fact that offspring from germ-free mothers are highly susceptible to metabolic syndrome, even when reared under conventional conditions. Thus, our findings elaborate on a link between the maternal gut environment and the developmental origin of metabolic syndrome.

Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants

BackgroundClostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains.MethodsC. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis.Results29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC.ConclusionsApproximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC.Trial registrationclinicaltrials.govNCT01102738, registered 13th April 2010.

Epidural-Related Fever and Maternal and Neonatal Morbidity: A Systematic Review and Meta-Analysis

Background: While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. Objectives: The aim of this systematic review was to investigate the effect of epidural-related intrapartum fever on maternal and neonatal outcomes. Methods: OVID MEDLINE, OVID Embase, the Cochrane Library, Cochrane Controlled Register of Trials, and clinical trial registries were searched for randomized controlled trials (RCT) and observational cohort studies from inception to November 2018. A total of 761 studies were identified with 100 eligible for full-text review. Only articles investigating the relationship between EA and maternal fever during labor were eligible for inclusion. Study quality was assessed using the Cochrane’s Risk of Bias tool and National Institute of Health Quality Assessment Tool. Two meta-analyses – one each for the RCT and observational cohort groups – were performed using the random-effects model of Mantel-Haenszel to produce summary risk ratios (RR) with 95% CI. Results: Twelve RCTs and 16 observational cohort studies involving 579,157 parturients were included. RRs for maternal fever for the RCT and cohort analyses were 3.54 (95% CI 2.61–4.81) and 5.60 (95% CI 4.50–6.97), respectively. Meta-analyses of RR for maternal infection in both groups were infeasible given few occurrences. Meta-analysis of data from observational studies showed an increased risk for maternal antibiotic treatment in the epidural group (RR 2.60; 95% CI 1.31–5.17). For both analyses, neonates born to women with an epidural were not evaluated more often for suspected sepsis. Neither analysis reported an increased rate of neonatal bacteremia or neonatal antibiotic treatment after EA, although data precluded conclusiveness. Conclusion: EA increases the risk of intrapartum fever and maternal antibiotic treatment. However, a definite conclusion on whether EA increases the risk for a proven maternal and/or neonatal bacteremia cannot be drawn due to the low quality of data. Further research on whether epidural-related intrapartum fever is of infectious origin or not is therefore needed.

Factors associated with development of early and late pulmonary hypertension in preterm infants with bronchopulmonary dysplasia.

ObjectiveTo investigate factors associated with development of early and late pulmonary hypertension (E/LPH) in preterm infants with bronchopulmonary dysplasia (BPD).Study designA retrospective case-control observational study of preterm infants with BPD admitted to a level IV referral neonatal intensive care unit over 5 years. We compared pre- and postnatal characteristics between infants with or without BPD-associated EPH and LPH.ResultsFifty-nine out of 220 infants (26.8%) had LPH, while 85 out of 193 neonates (44%) had EPH. On multiple logistic regression, novel factors associated with development of BPD–LPH included presence of maternal diabetes, EPH, tracheostomy, tracheitis, intraventricular hemorrhage (IVH, grade ≥3) and systemic steroid use. For EPH, these were maternal diabetes, IVH grade ≥3, high frequency ventilator use, and absence of maternal antibiotics use.ConclusionWe identified novel factors and confirmed previously established factors with development of LPH and EPH, which can help develop a screening strategy in BPD patients.

Longitudinal Colonization With Streptococcus pneumoniae During the First Year of Life in a Healthy Newborn Cohort.

The objective of this study was to characterize longitudinal colonization with Streptococcus pneumoniae during the first year of life within a community newborn infant cohort, and assess the relationship between antibiotic exposure and colonization with antibiotic-resistant organisms. During April 2013-February 2014, 326 infants were enrolled from an urban academic hospital well-baby nursery. At ages 4, 8, and 12 months, we collected antibiotic data, other exposure data, and nasopharyngeal cultures for pneumococcal isolation. Follow-up visits were completed for 211, 158, and 144 infants at ages 4, 8, and 12 months, respectively. By 12 months, 33% of infants attending the visits had ever been exposed to antibiotics, 67% if exposures to maternal antibiotics at birth are included. Pneumococci were isolated at 38/839 (4.5%) visits from 38 infants, including one 13-valent conjugate vaccine (PCV13) serotype (6A). There were 1 (0.3%), 15 (7%), 7 (4%), and 15 (10%) infants who were colonized at 0-, 4-, 8-, and 12-month visits, respectively. By age 12 months, at least 35 (11%) infants had ever been colonized. Sixteen isolates (42%) exhibited nonsusceptibility to at least 1 antibiotic. Infants with recent antibiotic exposure were not more likely to be colonized or to harbor nonsusceptible organisms. Within a hospital birth cohort followed in the community, pneumococcal colonization and related antibiotic resistance were lower than previously reported, likely associated with PCV13 use. Antibiotic exposure was not associated with subsequent colonization with resistant isolates. The influence of other environmental factors needs further study.

Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia.

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.

Temporal development of the infant gut microbiome.

The majority of organisms that inhabit the human body reside in the gut. Since babies are born with an immature immune system, they depend on a highly synchronized microbial colonization process to ensure the correct microbes are present for optimal immune function and development. In a balanced microbiome, symbiotic and commensal species outcompete pathogens for resources. They also provide a protective barrier against chemical signals and toxic metabolites. In this targeted review we will describe factors that influence the temporal development of the infant microbiome, including the mode of delivery and gestational age at birth, maternal and infant perinatal antibiotic infusions, and feeding method—breastfeeding versus formula feeding. We will close by discussing wider environmental pressures and early intimate contact, particularly between mother and child, as they play a pivotal role in early microbial acquisition and community succession in the infant.

Maternal Peripartum Antibiotic Exposure Worsens Experimental Bronchopulmonary Dysplasia

Purpose: Recent reports indicate that early antibiotic exposure may worsen the severity of bronchopulmonary dysplasia (BPD) in very low birthweight infants. The mechanisms mediating worsened outcomes are unknown, but antibiotic exposure directly perturbs the intestinal microbiome stability and emerging evidence suggests the intestinal microbiota may influence systemic inflammation. Accordingly, we investigated if alteration of the intestinal microbiota altered the development of hyperoxic lung injury in neonatal mice. Methods: We created a two-exposure model that randomized pregnant C57BL/6J mice on the tenth day of gestation to maternal antibiotic treatment (penicillin 500mg/L, MAT) or control. After birth, newborn offspring were randomized to hyperoxia (FiO2 0.85 or 0.60) or FiO2 0.21 for 14 …

Outcome of Late-onset Neonatal Sepsis at a Tertiary Hospital in Oman.

ObjectivesWe sought to determine the prevalence, pattern of causative organisms, and mortality of newborns with culture-proven late-onset sepsis (LOS) and to determine and compare the risk factors linked to late-onset gram-positive and late-onset gram-negative sepsis in Sultan Qaboos University Hospital (SQUH).MethodsWe conducted a cross-sectional retrospective study of data obtained between 1 January 2007 and 31 December 2014 (eight years) from infants in the neonatal intensive care unit (NICU) at SQUH. Infants born in SQUH (inborn) and other institutions (outborn) with positive blood cultures were included in the study.ResultsThe total number of live births and admissions during the study period were 26 289 and 3559, respectively. The total number of infants identified with LOS were 125 of whom 69 (55.2%) were gram-positive, 52 (41.6%) were gram-negative, and four (3.2%) were due to Candida species (spp.). The majority of infants (n = 113, 90.4%) were inborn; 69 (55.2%) were males and 56 (44.8%) were females. The prevalence of LOS among inborn admissions was 4.3 per 1000 live births. Most infections occurred in very low birth weight infants (n = 81, 64.8%). Eleven (8.8%) infants died due to gram-negative sepsis. Klebsiella pneumoniae followed by Pseudomonas aeruginosa were the leading cause of death. Maternal intrapartum antibiotics were the only independent risk factor correlating with gram-negative organisms in multivariate analysis (p = 0.003).ConclusionsLOS poses a burden in the NICU, which could be due to the increasing survival of premature babies. The main contributing organisms to LOS are gram-positive bacteria. Klebsiella spp. is a major cause of mortality in LOS. The use of intrapartum antibiotic prophylaxis in mothers might explain the positive correlation of maternal antibiotics as a risk factor with gram-negative infections.

Maternal use of antibiotics and cancer incidence risk in offspring: A population-based cohort study in Manitoba, Canada.

Several epidemiological studies have found an association between maternal antibiotics use during pregnancy and increased risk of certain cancer types, although conclusions differ between studies. We examined this association in a cohort study including 262 116 mother‐child pairs of Manitoba births between 1996 and 2013. Maternal antibiotics use during prepregnancy (6 months prior to pregnancy) and pregnancy periods was assessed. Children's cancer incidence was tracked up to the end of the follow‐up period (December 2015). We calculated incidence rate and used Cox regression to estimate adjusted hazard ratios (HRs). Antibiotics use during pregnancy was not associated with overall cancer (HR = 1.1, 95% confidence interval 0.9‐1.4), leukemias (1.3, 0.9‐1.8), or acute lymphocytic leukemia (1.1, 0.7‐1.6). The association between antibiotics use and overall cancer risk differed by trimester: 1.5 (1.1‐1.9) in the first, 0.8 (0.6‐1.0) in the second, and 1.1 (0.8‐1.5) in the third trimester. Further research is necessary to confirm the association between first‐trimester exposure and cancer risk after a better controlling of confounding factors.

Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers?

ObjectiveTo examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks’ gestation.DesignA retrospective cohort study.SettingData collected by the Canadian Neonatal Network.PatientsNeonates born at <29...

Impact of maternal intrapartum antibiotics on the initial oral microbiome of neonates

Prior studies have proposed that maternal intrapartum antibiotic exposure shapes the gut microbiota and, subsequently the child's health. However, the effect of maternal intrapartum antibiotic exposure and its influence on the development of the neonatal oral microbiota in early infancy has not yet been reported. The aim of this study was to compare the initial oral microbiota immediately after birth of healthy infants with and without intrapartum antibiotic exposure. Twenty-two newborns of the BaoAn Maternal and Child Care Hospital (Shenzhen, China) were recruited for this study, 11 born to mothers without intrapartum antibiotic exposure (NT group) and 11 to mothers with intrapartum antibiotic prophylaxis with cefamezin (AT group). Oral microbiome profiles were determined by 16S rRNA sequencing based on the V3V4 hyper-variable regions. Phylum Firmicutes was most frequently detected in subjects both groups and a higher frequency was observed in the NT group than the AT group. Phyla Actinobacteria, Bacteroidetes and Proteobacteria were more abundant after intrapartum antibiotics exposure. Genus Lactobacillus belonging to Firmicutes was predominant in the neonates not exposed to antibiotics, while significantly higher percentages of genera Klebsiella, Roseburia, Propionibacterium, Faecalibacterium, Escherichia/Shigella, Corynebacterium, Bifidobacterium, and Bacteroides were noted in AT infants than NT infants. Further function analysis demonstrated that lipopolysaccharide biosynthesis and amino acid-related metabolic function was enriched in the AT group, and carbohydrate metabolism pathways were more abundant in the NT group. These findings revealed distinctions in both taxa and metabolic function of oral microbiota between antibiotics-treated and unexposed groups, which indicated that maternal intrapartum antibiotic treatment is a key regulator of the initial neonatal oral microbiome.

Effects of Early Intervention With Maternal Fecal Bacteria and Antibiotics on Liver Metabolome and Transcription in Neonatal Pigs.

The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>109/mL), respectively, on days 1–6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic–pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P < 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P < 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P < 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P < 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.