Manipulating the microbiome alters regenerative outcomes in Xenopus laevis tadpoles via lipopolysaccharide signalling

Wound Rep Reg, 2022 · DOI: 10.1111/wrr.13003 · Published: January 28, 2022

Regenerative Medicine Immunology Genetics

Simple Explanation

Xenopus laevis tadpoles can regenerate tails, but this ability varies during a specific refractory period. The study investigates how manipulating the tadpole skin microbiome, particularly through antibiotics, affects tail regeneration. The research focuses on lipopolysaccharides (LPS) from bacteria and their interaction with Toll-like receptor 4 (TLR4), exploring if LPS signaling influences regeneration outcomes. The study reveals that specific Gram-negative bacteria and their LPS can significantly enhance tail regeneration, while blocking TLR4 signaling impairs regeneration quality, suggesting a crucial role for the microbiome in tissue repair.

Study Duration

7 days post amputation

Participants

Xenopus laevis tadpoles (stage 46)

Evidence Level

Not specified

Key Findings

1
The tadpole skin microbiome varies significantly between sibships and is altered by raising tadpoles in the antibiotic gentamicin.
2
Six Gram-negative genera, including Delftia and Chryseobacterium, were over-represented in tadpoles that underwent tail regeneration.
3
LPS from commensal Chryseobacterium spp. XDS4 or from a Delftia spp. isolate can rescue regeneration in gentamicin-raised tadpoles.

Research Summary

This study investigates the role of the skin microbiome in tail regeneration of Xenopus laevis tadpoles during the refractory period, showing that microbiome composition varies between tadpole sibships and can be altered by antibiotic treatment. The research identifies specific Gram-negative bacteria, such as Delftia and Chryseobacterium, whose lipopolysaccharides (LPS) promote tail regeneration, and demonstrates that antagonistic LPS or CRISPR/Cas9 editing of TLR4 reduces regeneration quality. The findings suggest that LPS from Gram-negative bacteria enhances regenerative outcomes through a signaling pathway involving TLR4, highlighting the potential for microbiome manipulation to improve wound healing and regeneration.

Practical Implications

Therapeutic potential of LPS

LPS from specific bacteria can be used to enhance regenerative processes.

Microbiome-based therapies

Manipulating the microbiome composition to promote regenerative outcomes is a viable option.

Targeting TLR4

Targeting TLR4 signaling may improve medicinal and veterinary outcomes in wound healing and regeneration.

Study Limitations

1
TLR4 inhibition was not absolute, possibly due to competition from remaining TLR4 agonist microbes.
2
CRISPR/Cas9 editing did not achieve 100% editing in any tadpole, leading to mosaicism.
3
Parentage and antibiotic exposure of tadpoles is not always declared in other studies making comparisons difficult.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine