Dysbiosis of the gut microbiome, the collection of bacteria, virus and fungi inhabiting our gastrointestinal tract, has been associated to many diseases and pathological conditions and thus has gained large attention in the biomedical field. To robustly characterize influencing factors from the environment and from the host also in the healthy status, we performed the largest genetic study of human gut microbiome from a single population and using metagenomic sequencing in in 7,738 participants of the Dutch Microbiome Project. I will discuss the results identified also in the light of similar studies in other populations, discuss lessons learned, challenges and for future studies on gut microbiome aiming to understand interactions with the host genome and its role in shaping human biological functions.