Intestinal colonisation patterns in breastfed and formula-fed infants during the first 12 weeks of life reveal sequential microbiota signatures

Harro M Timmerman,Martin Kullen,Ger T Rijkers,Nicole B M M Rutten,Michiel Kleerebezem,Jos Boekhorst,Arine M Vlieger,Guus A M Kortman,Delphine M Saulnier,Nikhat Contractor,Esther Floris,Hermie J M Harmsen

doi:10.1038/s41598-017-08268-4

Abstract

The establishment of the infant gut microbiota is a highly dynamic process dependent on extrinsic and intrinsic factors. We characterized the faecal microbiota of 4 breastfed infants and 4 formula-fed infants at 17 consecutive time points during the first 12 weeks of life. Microbiota composition was analysed by a combination of 16S rRNA gene sequencing and quantitative PCR (qPCR). In this dataset, individuality was a major driver of microbiota composition (P = 0.002) and was more pronounced in breastfed infants. A developmental signature could be distinguished, characterized by sequential colonisation of i) intrauterine/vaginal birth associated taxa, ii) skin derived taxa and other typical early colonisers such as Streptococcus and Enterobacteriaceae, iii) domination of Bifidobacteriaceae, and iv) the appearance of adultlike taxa, particularly species associated with Blautia, Eggerthella, and the potential pathobiont Clostridium difficile. Low abundance of potential pathogens was detected by 16S profiling and confirmed by qPCR. Incidence and dominance of skin and breast milk associated microbes were increased in the gut microbiome of breastfed infants compared to formula-fed infants. The approaches in this study indicate that microbiota development of breastfed and formula-fed infants proceeds according to similar developmental stages with microbiota signatures that include stage-specific species.

Highlights

The approaches in this study indicate that microbiota development of breastfed and formula-fed infants proceeds according to similar developmental stages with microbiota signatures that include stagespecific species
We investigated the dynamics of the faecal microbiota during the first 12 weeks of life of vaginally delivered, healthy breastfed and formula-fed infants, using an integrative approach comprising complementary molecular technologies, namely 16S profiling, qPCR and FISH
Individuality was the strongest predictor of microbiota composition, which is in line with previous findings of a slightly larger study 8

Summary

Introduction

The approaches in this study indicate that microbiota development of breastfed and formula-fed infants proceeds according to similar developmental stages with microbiota signatures that include stagespecific species. The development of the intestinal microbiota is highly dynamic due to initial low stability, limited bacterial richness and low diversity of the ecosystem that is establishing[2, 5, 6]. This process differs considerably between individual infants, and depends upon multiple extrinsic factors including mode of delivery, type of nutrition, use of antimicrobials, and gestational age[7,8,9,10]. A recent study by[20], applying shotgun metagenomics, revealed that cessation of breastfeeding was one of the key factors driving maturation of the gut microbiome into an adultlike composition and functionally encoded capacity

Methods

Results

Conclusion