We investigate how microorganisms and their genomes, collectively known as microbiomes, influence the functioning of multicellular organisms in different ecosystems. Our research primarily focuses on the services provided by microbiomes associated with different human body sites, especially the gut microbiome, to human health. Gut microbes evolve symbiotic associations with the human host and dynamically interact with the environment, helping to circumvent hazards and improving the host’s biological competences. The gut microbiome influences an array of physiological functions, ranging from metabolism to neural and immune functions, and affects all aspects of human health and disease. This notion has been extended to other ecosystems (terrestrial and marine animals, soils, plants, etc.), where we investigate microbiomes as mediators of associated benefits. Furthermore, we examine the systems-level effects of microbiomes on interlinked ecosystems from humans to animals and the environment: In particular, the role of food system microbiomes on productivity, sustainability, safety and nutritional quality of foods.