Abstract
Recent work in our lab has uncovered an interesting connection between regeneration and the skin microbiome. Culturing tadpoles of the species Xenopus laevis in the antibiotic gentamicin has been shown to reduce the rate of successful tail regeneration following amputation. The addition of heat killed Escherichia coli to these gentamicin treated tadpoles rescued the successful regeneration phenotype. Furthermore, 16s rRNA sequencing showed that the skin microbiome of tadpoles in which regeneration was successful was distinct from those where regeneration failed. Successful regenerates correlated with high gram-negative skin microbiota levels, supporting the suggestion that gram-negative bacteria may play a role in regenerative success. This previous work also showed that activity in the NF-κB pathway increased upon amputation of the tadpole tail, indicating an immune response was triggered by the amputation process.
These discoveries led to the generation of a hypothesis: the exposure of host immune cells to skin microbes during tail amputation induces an immune response that is required to trigger regeneration in Xenopus laevis tadpoles. The primary immune receptor responsible for the recognition of gram-negative bacteria is Toll-like receptor 4 (Tlr4), which has evolved to recognise a major structural component in the outer membrane of gram-negative bacteria called Lipopolysaccharide (LPS). It is this interaction between host Tlr4 and bacterial LPS that may provide the link between skin microbiome and regeneration. This connection between skin microbiome and regenerative success of a complex appendage in a vertebrate system has not been published anywhere in the current literature and is incredibly exciting. Furthering our understanding in the rapidly evolving field of regeneration is crucial if we wish to one day apply this knowledge in a medical context.