Finally, we found that YHGTD downregulated the TLR4/MyD88/NF-κB signaling pathway in both the striatum and colon.<h4>Conclusion</h4>YHGTD alleviated TD symptoms through neuroprotective and anti-inflammatory mechanisms, accompanied by alterations in the microbiota composition, supporting its potential as a therapeutic option for TD. This evidence concerns the gene TLR4 and thanatophoric dysplasia.