Even though tremendous progress has been made in the last decades to elucidate the mechanisms of intestinal homeostasis, dysbiosis and disease, we are only at the beginning of understanding the complexity of the gut ecosystem and the underlying interaction networks. We are also only starting to unravel the mechanisms that pathogens have evolved to overcome the barriers imposed by the microbiota and host to exploit the system to their own benefit. Recent work in these domains clearly indicates that the 'traditional Koch's postulate', which state that a given pathogen leads to a distinct disease, are not valid for all 'infectious' diseases, but that a more complete and complex interpretation of the Koch's postulate is needed in order to understand and explain them.This review summarizes the current understanding of what defines a healthy gut ecosystem and highlights recent progress in uncovering the interplay between the host, its microbiota and invading intestinal pathogens. Based on these recent findings, we propose a new interpretation of the Koch's postulate, that we term 'ecological Koch's postulate'.