Metabolic profiling reveals spatially-distinct reprogramming of host central carbon metabolism during Trichinella spiralis infection

Abstract

The metabolic interplay between Trichinella spiralis (Ts) and its host remains a critical but underexplored aspect of trichinosis pathogenesis. Understanding how the parasite manipulates host metabolism is key to developing new diagnostic and therapeutic strategies. We employed targeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to investigate alterations in central carbon metabolism. Targeted metabolomic profiling of 23 central carbon metabolism–related metabolites were performed in serum and intestinal contents collected from Ts-infected and control C57BL/6J mice ( n = 6 per group) at 14 days post-infection. Serum (representing systemic changes) and intestinal contents (representing the local microenvironment). The infection induced distinct, spatially-specific metabolic reprogramming. In serum, we observed significant increases in sedoheptulose 7-phosphate and dihydroxyacetone phosphate, alongside a notable decrease in lactic acid. This profile suggests a systemic shift towards the pentose phosphate pathway and altered glycolysis, indicative of a host-wide immune and stress response. Conversely, the intestinal contents of infected mice showed significantly elevated levels of lactic acid and pyruvic acid, pointing to a localized inflammatory environment and intense nutrient competition. Notably, receiver operating characteristic (ROC) curve analysis identified serum lactic acid and intestinal pyruvic acid as potential biomarkers of infection. Ts infection fundamentally reprograms host central carbon metabolism in a tissue-specific manner, disrupting systemic energy balance while creating a metabolically distinct niche within the intestine. These findings provide novel insights into the metabolic pathogenesis of trichinosis and highlight key metabolites as potential targets for future diagnostic and therapeutic interventions.