Exploring the effects of low temperature stress on the intestine-hepatopancrea axis and serum metabolites in common carp (Cyprinus carpio)

Abstract

Global climate change has intensified extreme cold events, seriously threatening aquaculture productivity. Although it is recognized that low temperature stress adversely affect the growth and immune function of fish, the specific mechanisms governing the communication between multiple organs, especially the interaction between intestines and hepatopancreas, are still not clear. To reveal the effects of low temperature stress on the intestine-hepatopancrea axis and serum metabolites in common carp (Cyprinus carpio), 120 common carp were divided into 2 groups, including normal temperature group (NT, 25 ± 1 °C) and low temperature group (LT, 5 ± 1 °C). After 48 h low temperature stress, histomorphological, serum biochemical indexes, 16S rDNA sequencing and metabolomics analysis were executed. These results showed that low temperature stress led to intestinal morphological changes (decrease in the number of goblet cells and villus erosion), increased permeability, and triggered multiple stress-related responses including oxidative stress, inflammation, apoptosis, and pyroptosis, led to microbiota dysbiosis with reduced beneficial bacteria and increased pathogenic bacteria. Hepatopancreatic damage included blurred hepatocytes boundaries, nucleus pushed to the periphery, lipid aggregates depletion, elevated the levels of ALT, AST and LDH in serum, the occurrence of oxidative stress, inflammation, apoptosis and pyroptosis. Serum metabolomics analysis showed that ABC transporters, cholesterol metabolism, primary bile acid biosynthesis, nucleotide metabolism and efferocytosis were enriched, with reduced lysophospholipids and increased taurochenodeoxycholic acid. Compensatory responses to low temperature stress included the changes in tight junction protein (ZO-1, Occludin, Claudin-3 and Claudin-7 mRNA), anti-inflammatory (TGF-β and IL-10 mRNA) and anti-apoptotic (Bcl-2 mRNA), and probiotics (Caulobacter, Akkermansia and Phenylobacterium). In conclusion, low temperature stress disrupted intestinal barrier integrity and microbiota balance, induced hepatopancreatic structural damage and disorder of cholesterol and bile acid metabolism, ultimately establishing a “intestine leakage-hepatopancreatic injury-metabolic dysregulation” vicious cycle. These findings provide novel insights into the effects of low temperature on the intestine-hepatopancrea axis.