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The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth.

ABSTRACT: BACKGROUND:The impact of degree of prematurity at birth on premature infant gut microbiota has not been extensively studied in comparison to term infants in large cohorts. METHODS:To determine the effect of gestational age at birth and postnatal exposures on gut bacterial colonization in infants, we analyzed 65 stool samples from 17 premature infants in the neonatal intensive care unit, as well as 13 samples from 13 mostly moderate-to-late premature infants and 189 samples from 176 term infants in the New Hampshire Birth Cohort Study. Gut colonization patterns were determined with 16S rDNA microbiome profiling. RESULTS:Gut bacterial alpha-diversity differed between premature and term infants at 6 weeks of age, after adjusting for exposures (p?=?0.027). Alpha-diversity varied between extremely premature (<28 weeks gestation) and very premature infants (?28 but?<32 weeks, p?=?0.011), as well as between extremely and moderate-to-late premature infants (?32 and?<37 weeks, p?=?0.004). Newborn antibiotic use among premature infants was associated with lower Bifidobacterium and Bacteroides abundance (p?=?0.015 and p?=?0.041). CONCLUSION:Gestational age at birth and early antibiotic exposure have significant effects on the premature infant gut microbiota.

SUBMITTER: Chernikova DA

PROVIDER: S-EPMC6082716 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth.

Chernikova Diana A DA Madan Juliette C JC Housman Molly L ML Zain-Ul-Abideen Muhammad M Lundgren Sara N SN Morrison Hilary G HG Sogin Mitchell L ML Williams Scott M SM Moore Jason H JH Karagas Margaret R MR Hoen Anne G AG

Pediatric research 20180523 1

<h4>Background</h4>The impact of degree of prematurity at birth on premature infant gut microbiota has not been extensively studied in comparison to term infants in large cohorts.<h4>Methods</h4>To determine the effect of gestational age at birth and postnatal exposures on gut bacterial colonization in infants, we analyzed 65 stool samples from 17 premature infants in the neonatal intensive care unit, as well as 13 samples from 13 mostly moderate-to-late premature infants and 189 samples from 17 ...[more]

PMID: 29795209

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Project description:IntroductionVery Low Birth Weight (VLBW) infants, born weighing less than 1,500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. Behavioral effects, while related to neurodevelopment, are often more subtle and difficult to measure. The extent of later neurobehavioral consequences associated with such microbial dysbiosis has yet to be determined. We explored associations between the infants' gut microbiome and early childhood behavior at 4 years of age and identified the bacterial taxa through a multivariate analysis by linear models.MethodsParents completed the Child Behavior Checklist (CBCL) focused on different DSM diagnostic categories: affective, anxiety, pervasive developmental, attention deficit/hyperactivity, and oppositional defiant. All the CBCL scores were corrected for gender, delivery method, gestational age, infant birth weight, occurrence of sepsis, and days on antibiotics prior statistical analyses. Canonical correlation analysis (CCA) was performed to determine the relationship between early life gut microbiome and the adjusted CBCL scores. The association of bacterial Amplicon sequence Variants (ASVs) to the CBCL scores were tested with multivariate analysis by linear models (MaAsLin).ResultsNineteen children who were previously born with very low birth weight and studied while hospitalized in the Neonatal Intensive Care Unit (NICU) were included in this study. Statistically significant associations were observed between early life gut bacteria such as Veillonella dispar, Enterococcus, Escherichia coli, and Rumincococcus to later behavior at 4 years. No significant association could be observed with early-life gut microbiome alpha diversity and behavioral measures at 4 years.DiscussionThese preliminary observational data provide insight into the relationships between VLBW gut microbiome dysbiosis and childhood behavior. This study contributes to the literature on gut microbiome analysis by examining various behavioral domains using a standardized tool linked to the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Project description:BackgroundMother-to-newborn transmission of obesity-associated microbiota may be modified by birth mode (vaginal vs. Cesarean delivery). Prospective data to test this hypothesis are still sparse.ObjectiveTo examine prospective associations of maternal pre-pregnancy BMI and gestational weight gain with the infant gut microbiome by birth-mode strata.Subjects/methodsIn 335 mother-infant pairs in the New Hampshire Birth Cohort, we ascertained data from questionnaires and medical records, and generated microbiome data from 6-week-old infants' stool using Illumina 16s rRNA gene sequencing (V4-V5 region). Analyses were stratified by birth mode and conducted before and after adjusting for potential confounders, which included maternal age, education, parity, and Mediterranean diet score.ResultsAmong 335 mothers, 56% had normal pre-pregnancy BMI ( < 25, referent), 27% were overweight (BMI 25-30), and 18% obese (BMI > 30). Among the 312 mothers with weight gain data, 10% had inadequate weight gain, 30% adequate (referent), and 60% excess. Birth mode modified associations of pre-pregnancy BMI with several genera, including the most abundant genus, Bacteroides (P for interaction = 0.05). In the vaginal-delivery group, maternal overweight or obesity was associated with higher infant gut microbiome diversity and higher relative abundance of 15 operational taxonomic units (OTUs), including overrepresentation of Bacteroides fragilis, Escherichia coli, Veillonella dispar, and OTUs in the genera Staphylococcus and Enterococcus. In the Cesarean-delivered group, there were no significant associations of pre-pregnancy BMI with infant microbiome (alpha) diversity or OTUs. Gestational weight gain was not associated with differential relative abundance of infant gut microbial OTUs or with measures of microbial diversity in infants delivered vaginally or by Cesarean section.ConclusionsAmong vaginally-delivered infants, maternal overweight and obesity was associated with altered infant gut microbiome composition and higher diversity. These associations were not observed in Cesarean-delivered infants, whose microbiome development differs from vaginally-delivered infants. Our study provides additional evidence of birth-mode dependent associations of maternal body weight status with the infant gut microbiota. The role of these associations in mediating the intergenerational cycle of obesity warrants further examination.

Project description:BACKGROUND:The neonatal intensive care unit (NICU) contains a unique cohort of patients with underdeveloped immune systems and nascent microbiome communities. Patients often spend several months in the same room, and it has been previously shown that the gut microbiomes of these infants often resemble the microbes found in the NICU. Little is known, however, about the identity, persistence, and absolute abundance of NICU room-associated bacteria over long stretches of time. Here, we couple droplet digital PCR (ddPCR), 16S rRNA gene surveys, and recently published metagenomics data from infant gut samples to infer the extent to which the NICU microbiome is shaped by its room occupants. RESULTS:Over 2832 swabs, wipes, and air samples were collected from 16 private-style NICU rooms housing very low birth weight (<?1500 g), premature (<?31 weeks' gestation) infants. For each infant, room samples were collected daily, Monday through Friday, for 1 month. The first samples from the first infant and the last samples from the last infant were collected 383 days apart. Twenty-two NICU locations spanning room surfaces, hands, electronics, sink basins, and air were collected. Results point to an incredibly simple room community where 5-10 taxa, mostly skin-associated, account for over 50% of the amplicon reads. Biomass estimates reveal four to five orders of magnitude difference between the least to the most dense microbial communities, air, and sink basins, respectively. Biomass trends from bioaerosol samples and petri dish dust collectors suggest occupancy to be a main driver of suspended biological particles within the NICU. Using a machine learning algorithm to classify the origin of room samples, we show that each room has a unique microbial fingerprint. Several important taxa driving this model were dominant gut colonizers of infants housed within each room. CONCLUSIONS:Despite regular cleaning of hospital surfaces, bacterial biomass was detectable at varying densities. A room-specific microbiome signature was detected, suggesting microbes seeding NICU surfaces are sourced from reservoirs within the room and that these reservoirs contain actively dividing cells. Collectively, the data suggests that hospitalized infants, in combination with their caregivers, shape the microbiome of NICU rooms.

Project description:Human milk is the gold standard of nutrition for infants, providing both protective and essential nutrients. Although much is known about milk from mothers giving birth to term infants, less is known about milk from mothers giving birth to premature infants. In addition, little is known about the composition and diversity of small molecules in these milks and how they change over the first month of lactation.The objective was to understand how milk metabolites vary over the first month of lactation in mothers giving birth to term and preterm infants.(1)H nuclear magnetic resonance (NMR) metabolomics was used to characterize metabolites that were present in micromolar to molar concentrations in colostrum (day 0-5 postpartum), transition milk (day 14), and mature milk (day 28) from mothers who delivered term (n = 15) and preterm (n = 13) infants. Principal components analysis, linear mixed-effects models (LMMs), and linear models (LMs) were used to explore the relation between infant maturity and the postpartum day of collection of milk samples.By using a standard NMR metabolite library, 69 metabolites were identified in the milks, including 15 sugars, 23 amino acids and derivatives, 11 energy-related metabolites, 10 fatty acid-associated metabolites, 3 nucleotides and derivatives, 2 vitamins, and 5 bacteria-associated metabolites. Many metabolite concentrations followed a similar progression over time in both term and preterm milks, with more biological variation in metabolite concentrations in preterm milk. However, although lacto-N-neotetraose (LMM, P = 4.0 × 10(-5)) and lysine (LM, P = 1.5 × 10(-4)) significantly decreased in concentration in term milk over time, they did not significantly change in preterm milk.Overall, the metabolic profile of human milk is dynamic throughout the first month of lactation, with more variability in preterm than in term milk and subtle differences in some metabolite concentrations. This trial was registered at clinicaltrials.gov as NCT01841268.

Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

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The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth.

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The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth.

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