In a changing and interconnected world, the functions of microbiomes have to be better understood in view of sustaining the health of the human population. Two important healthcare challenges of our time are linked to microbiomes in different ecosystems, notably the spread of antimicrobial resistance genes and the increasing prevalence of chronic diseases. One Health is a concept which recognises that human health is connected to the health of animals and the environment. One Health relies on interdisciplinary, systems-level approaches to health. The field of microbiology is currently undergoing a revolution driven largely by a shift away from classical reductionist approaches towards the study of microorganisms directly in their native environments through advanced analytical methods. These approaches are allowing us to unravel the interdependencies between microbiomes associated with animals, the environment and humans. Here, we propose a truly interdisciplinary doctoral training programme aimed at studying the interactions within and between microbiomes in relation to human health. We will focus on two main research areas which represent frontier research topics of immediate public health relevance: (i) the spread of antimicrobial resistance genes and their acquisition by clinically relevant microorganisms, and (ii) the role of the human microbiome in chronic diseases. The programme will leverage the existing world-leading expertise in microbiology and systems biology in Luxembourg. By regrouping individual doctoral research projects focused around the two themes, the MICROH doctoral training unit will generate important new knowledge on how to leverage system-wide big data for the management of human health in the future. Most importantly, by providing an excellent, interdisciplinary research and training environment, it will facilitate the education and training of the next generation of microbiome scientists with excellent skills and knowledge essential to pursuing successful career paths in the future.