Rapid urbanisation and global biodiversity loss are changing human microbial ecology, which is accelerated by the progressive loss of protective factors for example, contact with natural environments and animals, and less consumption of traditional foods. Early life represents a critical window both for optimal colonisation and immune system development. The frequency of caesarean section (CS) delivery is high and increasing in many parts of the world, and there is strong evidence that CS delivery has a marked influence on early colonisation, with depletion of strains of commensal bacteria. Colonisation of human ecological niches, particularly the gastrointestinal tract, parallels normal local and systemic immune development. CS delivery has been associated with increased risk of allergic diseases and there is emerging evidence that this is mediated by alterations of the microbiome. Small proof-of-concept studies have demonstrated that transfer of maternal vaginal microbes directly after elective CS delivery partially restores the offspring microbiome but transfer of maternal faecal microbes is needed for restoration of the offspring gut microbiome. Randomised clinical trials (RCTs) using microbiome seeding after CS delivery are underway and are anticipated to unravel if this procedure will impact microbial, immunological and metabolic programming, and decrease allergy risk. RCTs using prebiotics and probiotics for primary prevention of allergic diseases (primarily eczema) have been conducted, but large heterogeneity between studies have hampered meta-analysis and the development of specific practice guidelines. In the first RCT to test the biodiversity hypothesis, exposure to playground sand with added microbially diverse soil, led to shifts in the skin and gut bacterial communities and increases in immunoregulatory biomarkers compared with exposure to microbially poor sand (placebo). Collectively, appropriate health-supporting microbial exposures by optimised nutrition and a microbially diverse environment in early life may curb the epidemic rise in allergic diseases, however, considerably more research is needed before this can be translated into specific practice guidelines.