Intestinal microbiota may influence human physiology and disease risk due to the role it plays in mediating appropriate immune responses to harmful and innocuous antigens. Colonisation of the intestine in early life seems particularly important as it is the main environmental stimulus for immune system maturation. This is a dynamic process, which depends on both environmental and genetic factors. The pathogenesis of inflammatory bowel disease, such as Crohn's disease, involves genetic polymorphisms (e.g. CARD15/nucleotide-binding oligomerisation domain 2) related to an excessive inflammatory response to commensal microbiota and to its unbalanced composition. Atopic diseases have also been linked to imbalances in microbiota and to related genetic factors (e.g. TLR4 and CD14 genes), although these associations are still controversial. Research into the relationship between the genetic risk of developing celiac disease (human leukocyte antigen (HLA)-DQ2/DQ8) and the early colonisation process in infants at family risk of the disease has also reported that the HLA-DQ genotype could influence staphylococcal colonisation. Future observational studies considering both host genetics and microbiota could be critical in defining the complex host-microbe interactions and the respective role each plays in inflammatory disorders.