Early life determinants induce sustainable changes in the gut microbiome of six-year-old children

Abstract

While the association between early life determinants and the development of the gut microbiome composition in infancy has been widely investigated, a potential persistent influence of early life determinants on the gut microbial community after its stabilization at later childhood remains largely unknown. Therefore, we aimed to identify the association between several early life determinants and the gut microbiome composition in six-year-old children from the LISA birth cohort. A total number of 166 fecal samples were analyzed using 16S rRNA gene-based barcoding to assess bacterial diversity pattern. The bacterial profiles were investigated for their association with maternal smoking during pregnancy, mode of delivery, breastfeeding, antibiotic treatment between one and two years of age, gender and socioeconomic status (SES). While alpha and beta diversity of the infants' gut microbiome remained unaffected, amplicon sequence variants (ASVs) annotated to Firmicutes and Actinobacteria responded to early life determinants, mostly to feeding practice and antibiotics use. ASVs associated to Bacteriodetes remained unaffected. Our findings indicate that early life determinants could have a long-term sustainable effect on the gut microflora of six-year-old children, however, associations with early life determinates are weaker than reported for infants.

Figure 1

PCoA plot of beta diversity of the gut microbiome based on weighted Unifrac distances for the investigated early life determinants. Ellipses show the two groups of the early life determinants (antibiotics use (AB): yes/no, exclusive breastfeeding (eBF): yes/no, smoking during pregnancy: yes/no, C-section (Csec): yes/no, gender: female/male and socioeconomic status (SES): high/ml) under investigation (n = 166).

Figure 2

Relative abundance of the five genera and related ASVs responding to the investigated early life determinants tested (antibiotics use during age 1–2 years (AB), exclusively breastfeeding (eBF), smoking during pregnancy, C-section (Csec), gender (female, male) and socioeconomic status (SES; high, ml)) (n = 166). Significant differences were calculated using multivariate ANOVA based on a linear mixed model (p value correction by Bonferroni method) and are indicated by asterisks (p < 0.05).