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Dichotomous development of the gut microbiome in preterm infants
Thao T B Ho1, Maureen W Groer1,2, Bradley Kane2
1Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Insights
Preterm infants often develop gut dysbiosis, with high levels of Gammaproteobacteria. Vaginal birth and antenatal steroids are linked to increased Gammaproteobacteria abundance in very low birth weight infants.
Area of Science:
- Neonatal microbiome research
- Gut microbial ecology in premature infants
Background:
- Preterm infants, especially very low birth weight (VLBW) infants, are susceptible to intestinal dysbiosis.
- An increased proportion of Gammaproteobacteria is a hallmark of dysbiosis in this population.
- Understanding the clinical factors influencing Gammaproteobacteria abundance is crucial for managing VLBW infants' gut health.
Purpose of the Study:
- To identify clinical determinants associated with the relative abundance of fecal Gammaproteobacteria in very low birth weight (VLBW) infants.
- To characterize the temporal dynamics of Gammaproteobacteria in the developing gut microbiome of preterm infants.
- To explore potential sources and influencing factors of Gammaproteobacteria colonization.
Main Methods:
- Fecal microbiome analysis using 16S rRNA amplicon sequencing at multiple time points (≤2 weeks, 3rd week, 4th week postpartum).
- Extraction of maternal and infant clinical data from electronic medical records.
- Statistical analysis employing linear mixed modeling and linear regression to identify associations.
Main Results:
- Fecal Gammaproteobacteria abundance significantly increased from ≤2 weeks to the 4th week postpartum (p < 0.001).
- Two distinct infant subgroups emerged: one with initially low and increasing Gammaproteobacteria, and another with high and decreasing abundance.
- Vaginal delivery and antenatal steroid administration were positively associated with increased Gammaproteobacteria abundance.
Conclusions:
- A dichotomy in gut microbiome assembly exists in preterm infants regarding Gammaproteobacteria colonization.
- Vaginal birth and antenatal steroids are significant predictors of Gammaproteobacteria abundance in early and later infant stool samples.
- These findings contribute to a better understanding of gut microbiome development and potential dysbiosis in premature infants.
Background:
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.
Results:
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.
Conclusions:
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.
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