Jie Jia1,2,3,4, Pengcheng Xun5, Xinling Wang6, Ka He7,8, Qingya Tang1,3,4, Tian Zhang3,4,9, Ying Wang1,3,4, Wenjing Tang1,2, Lina Lu1,3,4, Weihui Yan1,3,4, Weiping Wang9, Tianyi Hu2, Wei Cai1,3,4,9. 1. Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China. 2. Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China. 3. Shanghai Institute of Pediatric Research, Shanghai, P. R. China. 4. Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, P. R. China. 5. Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, IN, USA. 6. Department of Obstetrics, Hebei General Hospital, Shijiazhuang, Hebei, P. R. China. 7. Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA. 8. Department of Epidemiology, Columbia University, New York, NY, USA. 9. Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China.
Abstract
BACKGROUND: The early-life gut microbiota, which is critically important for the long-term health of infants, is normally sensitive to perturbations, especially in preterm infants. However, how the gut microbiota develops and what key factors affect the preterm gut microbiota remain largely unknown. We hypothesized that preterm microbial dysbiosis exists from the beginning after birth, and microbial alteration is associated with parenteral nutrition and antibiotic therapy interventions. METHODS: Fecal samples were collected from fifty-one preterm and fifty full-term vaginally delivered (FTVD) infants at 7 time points for 90 days after birth. The microbial profiles of 558 fecal DNA samples were analyzed by sequencing their 16S ribosomal RNA amplicons. A random-effects generalized least square regression was used to identify factors that influence the bacterial composition over time. RESULTS: The altered gut microbiota in preterm infants existed from the meconium, having significantly lower levels of Escherichia-Shigella than those in FTVD infants. The developmental trajectories of 7 predominant bacterial groups successfully fitted with exponential/linear function curves (R2 , 0.921-0.993) in both groups. By day 90, depleted levels of Bacteroides and Parabacteroides and an overabundance of Peptoclostridium were characteristic of the preterm group. The prolonged use of antibiotics and parenteral nutrition had significant adverse effects on the Lactobacillus and Bifidobacterium levels in preterm infants. Moreover, gestational age, sex, and birth weight were factors impacting specific genera in preterm infants. CONCLUSION: The early-life microbial composition and functions were markedly different in preterm infants, being associated with the prolonged use of postnatal antibiotics and parenteral nutrition.
BACKGROUND: The early-life gut microbiota, which is critically important for the long-term health of infants, is normally sensitive to perturbations, especially in preterm infants. However, how the gut microbiota develops and what key factors affect the preterm gut microbiota remain largely unknown. We hypothesized that preterm microbial dysbiosis exists from the beginning after birth, and microbial alteration is associated with parenteral nutrition and antibiotic therapy interventions. METHODS: Fecal samples were collected from fifty-one preterm and fifty full-term vaginally delivered (FTVD) infants at 7 time points for 90 days after birth. The microbial profiles of 558 fecal DNA samples were analyzed by sequencing their 16S ribosomal RNA amplicons. A random-effects generalized least square regression was used to identify factors that influence the bacterial composition over time. RESULTS: The altered gut microbiota in preterm infants existed from the meconium, having significantly lower levels of Escherichia-Shigella than those in FTVD infants. The developmental trajectories of 7 predominant bacterial groups successfully fitted with exponential/linear function curves (R2 , 0.921-0.993) in both groups. By day 90, depleted levels of Bacteroides and Parabacteroides and an overabundance of Peptoclostridium were characteristic of the preterm group. The prolonged use of antibiotics and parenteral nutrition had significant adverse effects on the Lactobacillus and Bifidobacterium levels in preterm infants. Moreover, gestational age, sex, and birth weight were factors impacting specific genera in preterm infants. CONCLUSION: The early-life microbial composition and functions were markedly different in preterm infants, being associated with the prolonged use of postnatal antibiotics and parenteral nutrition.