Strain inheritance and neonatal gut microbiota development: a meta-analysis

ABSTRACT As many inflammatory and metabolic disorders have been associated with structural deficits of the human gut microbiota, the principles and mechanisms that govern its initialization and development are of considerable scientific interest and clinical relevance. However, our current understanding of the developing gut microbiota dynamics remains incomplete. We carried out a large-scale, comprehensive meta-analysis of over 1900 available metagenomic shotgun samples from neonates, infants, adolescents, and their families, using our recently introduced SameStr program for strain-level microbiota profiling and the detection of microbial strain transfer and persistence. We found robust associations between gut microbiota composition and age, as well as delivery mode which was measurable for up to two years of life. C-section was associated with increased relative abundances of non-gut species and delayed transition from a predominantly oxygen-tolerant to intolerant microbial community. Unsupervised networks based on shared strain profiles generated family-specific clusters connecting infants, their siblings, parents and grandparents and, in one case, suggested strain transfer between neonates from the same hospital ward, but could also be used to identify potentially mislabeled metagenome samples. Following birth, larger quantities of strains were shared between vaginally born infants and their mothers compared to C-section infants, which further persisted throughout the first year of life and belonged to the same bacterial species as strains that were shared between adults and their parents. Irrespective of delivery type, older children shared strains with their mothers and fathers and, into adulthood, could be accurately distinguished from unrelated sample pairs. Prominent gut commensal bacteria were both among frequently transferred (e.g. Bacteroides and Sutterella ) and newly acquired taxa (e.g. Blautia, Faecalibacterium , and Ruminococcus ). Our meta-analysis presents a more detailed and comprehensive picture of the highly dynamic neonatal and infant gut microbiota development than previous studies and presents evidence for taxonomic and functional compositional differences early in life between infants born naturally or by C-section, which persist well into adolescence.