The gut-liver axis plays a limited role in mediating the liver's heat susceptibility of Chinese giant salamander.

The Chinese giant salamander (CGS, Andrias davidianus), a flagship amphibian species, is highly vulnerable to high temperatures, posing a significant threat under future climate change. Previous research linked this susceptibility to liver energy deficiency, accompanied by shifts in gut microbiota and reduced food conversion rates, raising questions about the role of the gut-liver axis in mediating heat sensitivity. This study investigated the responses of Chinese giant salamander larvae to a temperature gradient (10-30 °C), assessing physiological changes alongside histological, gut metagenomic, and tissue transcriptomic analyses. Temperatures above 20 °C led to mortality, which resulted in delayed growth. Histological and transcriptomic data revealed metabolic exhaustion and liver fibrosis in heat-stressed salamanders, underscoring the liver's critical role in heat sensitivity. While heat stress altered the gut microbiota's community structure, their functional profiles, especially in nutrient absorption and transformation, remained stable. Both gut and liver showed temperature-dependent transcriptional changes, sharing some common variations in actins, heat shock proteins, and genes related to transcription and translation. However, their energy metabolism exhibited opposite trends: it was downregulated in the liver but upregulated in the gut, with the gut showing increased activity in the pentose phosphate pathway and oxidative phosphorylation, potentially countering metabolic exhaustion. Our findings reveal that the liver of the larvae exhibits greater thermal sensitivity than the gut, and the gut-liver axis plays a limited role in mediating thermal intolerance. This study enhances mechanistic understanding of CGS heat susceptibility, providing a foundation for targeted conservation strategies in the face of climate change.