Dynamic interactions within the host associated microbiota cause tumorigenesis in the basal metazoan Hydra

Interactions between microorganisms and their eukaryotic hosts have shaped the evolution of complex life forms - plants and animals. All extant multicellular organisms contain abundant and diverse microbiota, and are considered as metaorganisms or holobionts. It is widely accepted that an intricate balance between cell dynamics within the host, associated microbiota, and their proper adjustment to the environment maintain the integrity of such a metaorganism. However, it remains unclear, to what extent disturbances in the resident microbiota can compromise an animal’s health. The fundamental mechanisms coupling the host homeostasis and microbiota and their evolutionary history remain poorly understood. The use of experimentally traceable and evolutionary informative models, such as cnidarians, may provide deep insights into the fundamental rules governing the host-microbiota interdependency. Here, I investigate the dynamic interactions between the microbiota and its host within the metaorganism Hydra. I demonstrate that alterations in the composition of commensal microbiota cause tumorigenesis in Hydra. Natural infestation of Hydra by environmental spirochaetes Turneriella or their experimental introduction greatly disturb normal development, morphogenesis, and tissue homeostasis of Hydra, resulting in tumor phenotype. Surprisingly, elimination of spirochaetes obliterates the tumor, indicating that a persistent presence of these bacteria is necessary to sustain tumorigenesis. I also show that, unexpectedly, virulence of the spirochaetes requires the presence of Pseudomonas spec., a member of Hydra´s beneficial microbiome. Finally, by integrating genomic and transcriptomic data, I uncover putative molecular mechanisms of the dynamic interactions between the resident bacterium Pseudomonas, an environmental spirochaete Turneriella, and the host that promote the tumor formation. Taken together, my observations point to the crucial role of commensal bacteria in maintaining tissue homeostasis and add support to the view that microbial community interactions are essential for disease. My findings in an organism that shares deep evolutionary connections with all animals, including the human human, have significant implications for our understanding of normal homeostasis within a holobiont and tumorigenesis.