Summary Life as we know it is built on intimate associations between organisms, and our bodies contain as many microbial cells as human. Yet fundamental questions about the effect on the host of within or between species diversity of microbes, or what happens to the microbiome if the host genetics vary, remain unanswered. Adult stem cells isolated from tissues, such as stomach or gut, can be coaxed to differentiate into miniature organs. These so-called organoids have been used to study tissue development and host response to infection from a clinical perspective. In contrast, we will use an eco-evolutionary framework to understand how microbe and host diversity affect the establishment and outcome of symbiotic interactions across the animal kingdom.