Integrated Multi-omics Analysis Identifies PPAR Signaling Network Associations with Metabolic-Immune Dysregulation and Intestinal Injury in PDCoV-Infected Piglets

ABSTRACT:

Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes severe diarrhea and high mortality in neonatal piglets and has demonstrated the capacity to infect human cells. However, the host response networks that govern disease outcome remain poorly understood. Here, we performed integrated transcriptomic, proteomic, and metabolomic profiling of jejunal tissues from PDCoV-infected piglets, representing the first such analysis in the primary target organ of this pathogen. Multi-omics integration identified a core host-response network characterized by concurrent activation of a potent type I interferon-mediated antiviral response and notable alterations in lipid metabolism. The peroxisome proliferator-activated receptor (PPAR) signaling pathway was among the most significantly enriched pathways, marked by coordinated upregulation of LPL, FABP3, and SCD and downregulation of SLC27A2. Metabolomic analysis demonstrated widespread degradation of membrane glycerophospholipids and alterations in the arachidonic acid–prostaglandin inflammatory axis, as evidenced by substrate consumption and accumulation of the pro-inflammatory mediator 20-hydroxy-PGE2. We propose a hypothetical working model in which PDCoV infection is associated with PPAR network modulation, potentially contributing to lipid resource reallocation and the establishment of a pro-inflammatory microenvironment that may exacerbate intestinal injury. Notably, similarities can be observed between these PDCoV-associated alterations and the metabolic-immune dysregulation reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising the hypothesis of shared pathogenic features across coronaviruses. Our findings highlight the PPAR pathway and its downstream lipid mediators as potential therapeutic targets warranting further investigation, and suggest that existing PPAR agonists may merit evaluation as candidate drugs for repurposing in future studies.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14236 | MetaboLights | 2026-04-15

REPOSITORIES: MetaboLights