Integrated microbiome-metabolome reveals thiram aggravates tibial dyschondroplasia through disturbing sphingolipid metabolism

Abstract

Abstract As a pesticide, thiram is widely used in agriculture to eliminate pests, and it also causes great environmental pollution and poses a certain threat to animal health. It’s well known that the contamination of feed with thiram in the environment can lead to tibial chondrogenesis(TD) in chickens. The imbalance of intestinal flora and related metabolites is closely related to bone development. Unfortunately, the relationship between the intestinal flora of TD broilers and serum metabolites is unclear. Our results demonstrated that broilers exposed to thiram showed typical lameness and the white cartilage thrombus in the growth plate, accompanied by hepatotoxicity and intestinal injury. We found that the intestinal flora of TD group was out of balance, the diversity was significantly increased with Corynebacterium significantly enriched. Moreover, the metabolome results showed alterations in 10 serum metabolites, with Glucosylceramide being considerably up-regulated, resulting in sphingolipid metabolism problem, which is critical in the etiology of TD. The comprehensive correlation analysis showed the relationship between intestinal microflora and Sphingolipid metabolism in TD broilers. Thiram aggravates tibial chondrodysplasia by affecting the changes in the composition and structure of the intestinal microflora of broilers and the disorder of sphingomyelin metabolism. Collectively, these findings provide novel insight into the pathogenesis of TD from the perspective of thiram-induced gut microbiota and metabolic disorders.