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In many research fields, men and women are often treated in the same way, while they do show differences in the pathogenesis of several diseases, including intestinal diseases such as inflammatory bowel disease (IBD). Our gut microbiota play a major role in health and disease and are in close contact with our intestinal immune system. The sex biases in intestinal diseases suggest the existence of sex differences in both microbiota composition and immune responses. Therefore, we investigated the effect of sex on the intestinal immune system and microbiota composition. Additionally we determined the effect of genetic background, age and reproductive condition, as these factors may interfere with the potential sex effects. We demonstrated sex differences in intestinal immunity and microbiome, however, these were dependent on mouse strain, age and reproductive status. Young healthy male and female mice had different microbiomes and intestinal immune responses that may benefit their sex specific needs. It seems likely that sex hormones are involved in these differences, since this is also the case for peripheral immune responses and pregnancy changed both the microbiota and intestinal immune composition. The sex differences in microbiota composition disappeared at an old age, while most sex differences intestinal immunity were maintained in old mice. This suggests that immune differences develop at a young age and are permanent, and that the age induced changes in the microbiome have no effect on the intestinal immunity. These findings may contribute to the development of more sex specific treatments for intestinal related …