Perinatal factors affect the gut microbiota up to four years after birth

Abstract

Perinatal factors impact gut microbiota development in early life, however, little is known on the effects of these factors on microbes in later life. Here we sequence DNA from faecal samples of children over the first four years and reveal a perpetual evolution of the gut microbiota during this period. The significant impact of gestational age at birth and delivery mode on gut microbiota progression is evident in the first four years of life, while no measurable effects of antibiotics are found in the first year. Microbiota profiles are also characteristic in children dependant on gestational age and maturity. Full term delivery is characterised by Bacteroides (year one), Parabacteroides (year two) and Christensenellaceae (year four). Preterm delivery is characterised by Lactobacillus (year one), Streptococcus (year two) and Carnobacterium (year four). This study reveals that the gut retains distinct microbial profiles of perinatal factors up to four years of age.

Fig. 1

Samples separate based on year and gestational age at birth. a Redundancy analysis (RDA) of operational taxonomic units (OTUs) (top 1000 OTUs present) showing separation of samples by year. b Canonical correspondence analysis (CCA) on OTUs, with samples shown at year one, two and four. Source data are provided as a Source Data file. (*p < 0.05, **p < 0.01, ***p < 0.001)

Fig. 2

Alpha diversity increases with age. Alpha diversity shown as Shannon Index and Evenness based on a year of sample and b gestational age at birth. Source data are provided as a Source Data file. (*p < 0.05, **p < 0.01, ***p < 0.001)

Fig. 3

Separation of samples using beta diversity data based on age and gestational age at birth. a Principal coordinate analysis (PCoA) based on Bray–Curtis operational taxonomic unit (OTU) data on independent samples at years one, two and four (individuals sampled at one time point). b PCoA based on Bray–Curtis OTU data on independent samples based on gestational age at birth. c Adonis variance analysis based on Bray–Curtis distance matrices at OTU level. Source data are provided as a Source Data file. (*p < 0.05, **p < 0.01, ***p < 0.001)

Fig. 4

Factors influencing separation of samples based on beta diversity PCA+ using operational taxonomic units (OTUs; top 1000 OTUs) and metadata from infants at years one, two and four. Source data are provided as a Source Data file

Fig. 5

Microbiota associated with the age of the infant. Heatmap based on top 100 genera clustered based on year. Values range from low (red) to high (yellow). Source data are provided as a Source Data file

Fig. 6

Taxa associated with the age of the individual. a Sparse Partial Least Squared–Discriminative Analysis plot illustrating a clear separation on repeated measures between years one, two and four using the top 1000 most abundant genera. b The associated contribution plot illustrating taxa associated with each year. Source data are provided as a Source Data file