The last decade has witnessed a meteoric rise in research focused on characterizing the human microbiome and identifying associations with disease risk. The advent of sequencing technology has all but eradicated gel-based fingerprinting approaches for studying microbial ecology, while at the same time traditional microbiological culture is undergoing a renaissance. Although multiplexed high-throughput sequencing is relatively new, the discoveries leading to this are nearly 50 years old, coinciding with the inaugural Microbiology Society Fleming Prize lecture. It was an honour to give the 2022 Fleming Prize lecture and this review will cover the topics from that lecture. The focus will be on the bacterial community in early life, beginning with term infants before moving on to infants delivered prematurely. The review will discuss recent work showing how human milk oligosaccharides (HMOs), an abundant but non-nutritious component of breast milk, can modulate infant microbiome and promote the growth of Bifidobacterium spp. This has important connotations for preterm infants at risk of necrotizing enterocolitis, a devastating intestinal disease representing the leading cause of death and long-term morbidity in this population. With appropriate mechanistic studies, it may be possible to harness the power of breast milk bioactive factors and infant gut microbiome to improve short- and long-term health in infants.