Examination of gene expression in S. mediterranea transitioning from recirculation to static culture in the presence or absence of Gentamycin at 0, 1, 2, 3, or 4 days

The interrelationship between endogenous microbiota, the immune system, and tissue regeneration is an area of intense research due to its potential therapeutic applications. In this study, we investigated the relationship between endogenous microbiota, host response, and regeneration in Schmidtea mediterranea, a model organism capable of regenerating any and all of its adult tissues. We performed deep sequencing of bacterial 16s rDNA under various perturbations to elucidate the composition and dynamics of the planarian microbiome. Microbiome characterization revealed a high Bacteroidetes to Proteobacteria ratio in healthy animals. Perturbations eliciting an expansion of Proteobacteria coincided with ectopic lesions and tissue degeneration. The culture of these bacteria yielded a strain of Pseudomonas capable of inducing progressive tissue degeneration. RNAi screening uncovered a TAK1 innate immune signaling module underlying compromised tissue homeostasis and regeneration during infection. TAK1/MKK/p38 signaling mediated opposing regulation of apoptosis during infection versus normal tissue regeneration. Given the complex role of inflammation in either hindering or supporting reparative wound healing and regeneration, this invertebrate model provides a basis for dissecting the duality of evolutionarily conserved inflammatory signaling in complex, multi-organ adult tissue regeneration.