Swine inflammation and necrosis syndrome is associated with plasma metabolites and liver transcriptome in affected piglets

Swine Inflammation and Necrosis Syndrome (SINS) can lead to severe clinical signs, especially in tails, ears, teats and claws in pigs. Clinical and histopathological findings in newborn piglets with in-tact epidermis indicate a primarily endogenous etiology, and microbial-associated molecular pat-terns (MAMPs), such as lipopolysaccharide (LPS) are assumed to play a central role in the devel-opment of the syndrome. We hypothesized that swine inflammation and necrosis syndrome (SINS) is indirectly triggered by gut-derived MAMPs entering the circulatory system via the liver and thereby causing derangements on liver metabolism. To test this hypothesis, metabolomes, candidate genes of the liver and liver transcriptomes of 6 piglets with high-grade clinical signs of SINS (SINS high) were examined and compared with 6 piglets without significant signs of SINS (SINS low). Several hepatic pro-inflammatory genes and genes involved in stress response were induced in piglets of the SINS high group. The most striking finding from hepatic transcript pro-filing and bioinformatic enrichment was that the most enriched biological processes associated with the approximately 220 genes induced in the liver of the SINS high group were exclusively related to metabolic pathways, such as fatty acid metabolic process. Within the genes (≈ 390) re-pressed in the liver of the SINS high group, enriched pathways were ribosome biogenesis, RNA processing, RNA splicing, spliceosome and RNA transport. The transcriptomic findings were supported by the results of the metabolome analyses. These results provide the first evidence for the induction of an inflammatory process in the liver of piglets suffering from SINS, accompanied by lipid metabolic derangement. For microarray analysis, n = 6 RNA samples each of the group SINS low and group SINS high were used for hybridization to the Affymetrix GeneChip Porcine Gene 1.0 Sense Target array.