Association between preterm infant gut microbiome and growth failure
PAS 2021 Virtual
April 30 – May 4, 2021
Infants born preterm and cared for in NICUs present unique challenges for clinical management, including increased exposure to antibiotics, insufficient volumes of mother’s own breast milk, and requirement for parenteral nutrition, which are associated with growth faltering. As a result, the developing gut microbiome is perturbed in preterm infants, which may lead to specific health and disease outcomes, particularly growth.
We hypothesized that there is an association between the development of the gut microbiome in preterm infants and their growth rate in the NICU.
Stool samples from 267 infants were collected longitudinally from infants with growth failure (GF, n=102) defined as birth to discharge weight Z score < -1.2, growth normal (GN, n=157), and infants who died (n=8). Extracted DNA was sequenced via shotgun metagenomic sequencing (Illumina NextSeq 2×150). Processed fastq files were mapped against the MetaPhlan2 marker gene database. Following quality control, metagenomic sequencing data was available for 2996 stool samples. To avoid repeated measures, discrete time periods were chosen; day of life (DOL) 0-9, 10-14, 15-19, 20-24, and 25-30.
Dirichlet multinomial mixtures clustered samples into six distinct microbiome ‘preterm gut community types’ (PGCTs) based on the overall bacterial profiles. PGCTs were numbered 1-6 according to the average age of samples within each PGCT (e.g., PGCT-1 consisted of the earliest samples). In comparison to PGCTs 1-3, GN infants were significantly more likely to be in PGCTs 4-6 at DOL 0-9 (odds ratio (OR) 2.82 (95% CI 1.2 – 6.6); P value 0.017), DOL 10-14 (OR 2.94 (95% CI 1.1 – 7.6); P value 0.026), DOL 15-19 (OR 2.34 (95% CI 1.1 – 5.1); P value 0.031), but not in the last two time points at DOL 20-24 (OR 1.95 (95% CI 1.0 – 3.9); P value 0.056) and DOL 25-30 (OR 1.28 (95% CI 0.6 – 2.6); P value 0.486). The bacterial species that were enriched in stages 4-6 included Escherichia coli, Clostridium perfringens, Bifidobacterium breve, Klebsiella pneumoniae, and Veillonella atypica.
These preliminary results demonstrate the potential to define distinct gut bacterial community types in preterm infants, which may have value for predicting growth status and informing clinical care to enhance growth. Excitingly, the strongest odds ratios were observed in the earliest time periods. Further work is needed to validate these findings and explore if modulating the gut microbiome in the first 20 days of life can improve growth outcomes in preterm infants.
A. Tandon 1 , C. Stewart 2 , D. Genetti 1 , J. Levesque 1 , D. Gallagher 1 , T. Warren 1
1 Astarte Medical , 2 Translational and Clinical Research Institute, Newcastle University,
Newcastle upon Tyne, UK,