Archaea, the third domain of life containing unique membrane composition and highly diverse cell wall structures, were only recognized 40 years ago. Initially identified in extreme environments, they are currently recognized as organisms ubiquitously present in most, if not all, microbiomes associated with eukaryotic hosts. However, they have been mostly overseen in microbiome studies due to the lack of standardized detection protocols and to the fact that no archaeal pathogen is currently known. Recent years clearly showed that (i) archaea are part of the microbiomes associated with plants, animals and humans, (ii) form biofilms and (iii) interact and activate the human immune system. Future studies will not only define the host-associated diversity of archaea (referred to as ‘archaeome’) but also contribute to our understanding of the comprehensive metabolic interplay between archaea and bacteria and the long-term gain insights into their role in human health and their potential role(s) during disease development.

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