This review summarises how the composition of the gastro-intestinal microbiota depends on pre- and postnatal factors, and birth itself. The impact of method of delivery, feeding during infancy and medications, such as antibiotics and anti-acid medication, on the composition of the gastro-intestinal microbiota has clearly been shown. However, the duration of the impact of these factors is not well established. The gastro-intestinal microbiome composition is associated with many auto-immune mediated diseases. Although causality has not been obviously demonstrated, there is a strong tendency in this direction. Nevertheless, results of the manipulation of the gastro-intestinal microbiome composition in these conditions are often disappointing. A better understanding on factors determining the longterm composition of the gastro-intestinal microbiome and its health consequences are a priority research topic. A better understanding of the association between the microbiome and the immune system may have a tremendous impact on general health.