The microbiome contributes to human development and maturation, and is essential for maintenance of health and prevention of disease. While the human genome encodes one’s identity, the microbiome – also individually unique – provides a window on one’s lifestyle and exposure to environmental variables. The microbiome thus serves as a biomarker of host health and a driver of certain diseases. However, current understanding of the gut microbiome is largely based on studies of industrialised peoples of North America and Europe. Gaps in knowledge of the microbiomes of other groups, particularly those in developing or nonindustrialised societies, are important, particularly in view of contrasting epidemiological risks of acquiring chronic inflammatory and metabolic disorders. Here, we explore underlying mechanisms of microbiome differences and whether the potential benefits of nonindustrialised microbiome can be realised in a modern world.