Towards understanding an ultimately simple metaorganism : impact of symbiotic microbes on developmental processes of Hydra
From plants to human, all multicellular life is in close contact with associated microbes. Animal-microbe interactions have a profound impact on host physiology and development. The metaorganism Hydra harbors species-specific microbiota with the help of an innate immune system and a rich repository of antimicrobial peptides. Hydra-associated microbiota protect the host against pathogenic fungal infections, and help maintain its neuronal activity and spontaneous body contraction. By using a newly established long-term germ-free (GF) Hydra system, this study uncovered a reversible budding-inhibition phenotype in the absence of microbes. Recolonizing the GF polyps with wildtype Hydra microbiota resulted in regular budding, thus totally rescued the phenotype. In addition, the budding-inhibited GF Hydra increased the body size by two-fold, and produced numerous number of ectopic buds along the body column extending the regular budding zone. Transcriptome analysis identified over 7,000 differentially expressed genes between Hydra with and without microbes, and provided a global view of the microbial colonization signature. Comparing the budding-inhibited polyps with regularly budding individuals produced a list of 2541 differentially expressed genes, with further insight into the budding-related gene expression changes. Overlapping both datasets resulted in a consensus 210 microbe-responsive and budding-related genes, including members of the TGF-β, Notch, and Foxo signaling pathways which are involved in Hydra development. Budding-essential genes, such as Wnt signaling components, and transcription factors known to play a role during early budding processes, were dysregulated in the budding-inhibited GF Hydra. In addition, nematoblast-related genes showed a coordinated down-regulation in GF Hydra. Therefore, Hydra microbiota seems to affect host development and tissue homeostasis by targeting both epithelial stem cells (which initiate budding) and cells from the interstitial cell lineage. Further analysis incorporating microbial metabolite data could help resolve the direct molecular interactions between Hydra and the associated microbiota, therefore offering a detailed molecular cascade underlying the budding inhibition in the GF polyps.