skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Dichotomous development of the gut microbiome in preterm infants

Journal Article · · Microbiome
 [1];  [2];  [3];  [4];  [1];  [5];  [6]
  1. Univ. of South Florida, Tampa, FL (United States). Dept. of Pediatrics. Morsani College of Medicine
  2. Univ. of South Florida, Tampa, FL (United States). Dept. of Pediatrics. Morsani College of Medicine. College of Nursing
  3. Univ. of South Florida, Tampa, FL (United States). College of Nursing
  4. Univ. of Chicago, IL (United States). Interdisciplinary Scientist Training Program. Microbiome Center. Dept. of Surgery
  5. Univ. of Chicago, IL (United States). Microbiome Center. Dept. of Surgery; Argonne National Lab. (ANL), Argonne, IL (United States)
  6. Univ. of South Florida, Tampa, FL (United States). Dept. of Pediatrics. Morsani College of Medicine; Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Pediatrics
+ Show Author Affiliations

Preterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression. Clinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0–90%) at ≤ 2 weeks, 69.7% (29.9–86.9%) in the 3rd, and 75.5% (54.5–86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids. We detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States); Univ. of South Florida, Tampa, FL (United States); Univ. of Chicago, IL (United States); Johns Hopkins Univ., Baltimore, MD (United States)
Sponsoring Organization:
USDOE; National Inst. of Health (NIH) (United States)
Grant/Contract Number:
AC02-06CH11357; NR015446; HL124078; HL133022; T32GM007281
OSTI ID:
1493912
Journal Information:
Microbiome, Vol. 6; ISSN 2049-2618
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 37 works
Citation information provided by
Web of Science

References (63)

Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study journal May 2016
Analysing repeated measurements data: a practical comparison of methods journal June 1999
Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity journal June 2017
The Effect of Betamethasone on Neonatal Neutrophil Chemotaxis journal August 1987
Intrapartum Magnesium Sulfate Exposure Attenuates Neutrophil Function in Preterm Neonates journal January 2006
Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants journal January 2014
Development of the Human Infant Intestinal Microbiota journal June 2007
Antibiotic perturbation of the preterm infant gut microbiome and resistome journal July 2016
Neonatal Hypermagnesemia and the Meconium-Plug Syndrome journal April 1972
Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy journal August 2006
Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome journal March 2016
The Application of Ecological Theory Toward an Understanding of the Human Microbiome journal June 2012
Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender journal April 2016
Epigenome-Microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease journal February 2016
Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid journal March 2016
Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis journal March 2017
Longitudinal Analysis of the Premature Infant Intestinal Microbiome Prior to Necrotizing Enterocolitis: A Case-Control Study journal March 2015
A roadmap of clustering algorithms: finding a match for a biomedical application journal December 2008
Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine journal February 2006
Biospecimen Reporting for Improved Study Quality (BRISQ): Letters to the Editor journal July 2013
Early pregnancy vaginal microbiome trends and preterm birth journal September 2017
16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis journal April 2009
The global health impact of vaginal dysbiosis journal November 2017
Model selection and psychological theory: A discussion of the differences between the Akaike information criterion (AIC) and the Bayesian information criterion (BIC). journal January 2012
Early Empiric Antibiotic Use in Preterm Infants Is Associated with Lower Bacterial Diversity and Higher Relative Abundance of Enterobacter journal July 2014
Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls journal July 2017
A core gut microbiome in obese and lean twins journal November 2008
Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants journal April 2013
Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development journal November 2015
Intestinal Microbial Ecology and Environmental Factors Affecting Necrotizing Enterocolitis journal December 2013
Influence of maternal breast milk ingestion on acquisition of the intestinal microbiome in preterm infants journal December 2016
On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other journal March 1947
The Placenta Harbors a Unique Microbiome journal May 2014
On the Interpretation of χ 2 from Contingency Tables, and the Calculation of P journal January 1922
Human milk microbiota profiles in relation to birthing method, gestation and infant gender journal January 2016
Differences in the Stool and Skin Microbiome, Virulence Factor and Antimicrobial Resistance Genes in a Private Room Versus a Shared Space Neonatal Intensive Care Unit journal April 2017
Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development journal March 2015
Culture independent assessment of human milk microbial community in lactational mastitis journal August 2017
Development of the preterm infant gut microbiome: a research priority journal January 2014
Biospecimen reporting for improved study quality (BRISQ) journal August 2012
Strain-resolved community genomic analysis of gut microbial colonization in a premature infant journal December 2010
Patterned progression of bacterial populations in the premature infant gut journal August 2014
DADA2: High-resolution sample inference from Illumina amplicon data journal May 2016
The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk journal January 2017
Altered Immune Function in Human Newborns after Prenatal Administration of Betamethasone: Enhanced Natural Killer Cell Activity and Decreased T Cell Proliferation in Cord Blood journal March 1999
The Selection of Variables in Multiple Regression Analysis journal September 1970
Mode of delivery affects the bacterial community in the newborn gut journal July 2010
The impact of collinearity on regression analysis: the asymmetric effect of negative and positive correlations journal March 2002
Association of antenatal steroid use with cord blood immune biomarkers in preterm births journal August 2011
Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms journal March 2012
Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns journal June 2010
The More the Merrier? Reduced Fecal Microbiota Diversity in Preterm Infants Treated with Antibiotics journal July 2014
Improved Bacterial 16S rRNA Gene (V4 and V4-5) and Fungal Internal Transcribed Spacer Marker Gene Primers for Microbial Community Surveys journal December 2015
Balance Trees Reveal Microbial Niche Differentiation journal January 2017
Epigenome-Microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease dataset January 2016
Epigenome-Microbiome crosstalk: A potential new paradigm influencing neonatal susceptibility to disease dataset January 2016
Necrotizing Enterocolitis: Treatment Based on Staging Criteria journal February 1986
The complete chloroplast genome of Gleditsia sinensis and Gleditsia japonica: genome organization, comparative analysis, and development of taxon specific DNA mini-barcodes journal October 2020
Additional maternal and nonmaternal factors contribute to microbiota shaping in newborns journal September 2010
Antibiotic-Induced Perturbations of the Intestinal Microbiota Alter Host Susceptibility to Enteric Infection journal August 2008
Antenatal Betamethasone Changes Cord Blood Monocyte Responses to Endotoxin in Preterm Lambs journal May 2004
Testing for Serial Correlation in Least Squares Regression. III journal April 1971
Analysis of composition of microbiomes: a novel method for studying microbial composition journal May 2015

Cited By (7)

A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions journal August 2019
Dysbiosis and Prematurity: Is There a Role for Probiotics? journal June 2019
Changes in the Composition of the Gut Microbiota and the Blood Transcriptome in Preterm Infants at Less than 29 Weeks Gestation Diagnosed with Bronchopulmonary Dysplasia journal October 2019
Effects of early life NICU stress on the developing gut microbiome journal January 2019
Development of the Gut Microbiome in Children, and Lifetime Implications for Obesity and Cardiometabolic Disease journal November 2018
Evolution of Gut Microbiome and Metabolome in Suspected Necrotizing Enterocolitis: A Case-Control Study journal July 2020
Nutrients and Microbiota in Lung Diseases of Prematurity: The Placenta-Gut-Lung Triangle journal February 2020

Linked Research (8)

Similar Records

Related Subjects

60 APPLIED LIFE SCIENCES
very low birth weight infant
Gammaproteobacteria
dysbiosis