In humans, the intestinal microbiome varies considerably from early life to adulthood. The composition and functions of the paediatric microbiome are key to ensure a healthy immune system in the long run. Microbiome perturbations during early life can occur around weaning — the infant’s transition from milk to a solid food diet — when the microbial community expands, and peripheral regulatory T cells (pTreg cells) start to develop to modulate long-term immunity. The precise host and microbial mechanisms that take place during weaning to sustain the healthy development of the immune system are currently unknown. In a recent study, Lubin et al. combine metagenomics and in vivo models to show that an immature microbial community during weaning impairs the development of the immune system in mice and increases the risk of enteric infections in adult mice.