Integrated Metabolomic and transcriptomic analyses reveal deoxycholic acid promotes transmissible gastroenteritis virus infection by inhibiting phosphorylation of NF-κB and STAT3.

BACKGROUND: Acute diarrhea, dehydration and death in piglets are all symptoms of transmissible gastroenteritis virus (TGEV), which results in significant financial losses in the pig industry. It is important to understand the pathogenesis and identify new antiviral targets by revealing the metabolic interactions between TGEV and host cells. RESULTS: We performed metabolomic and transcriptomic analyses of swine testicular cells infected with TGEV. A total of 1339 differential metabolites and 206 differentially expressed genes were detected post TEGV infection. The differentially expressed genes were significantly enriched in the HIF-1 signaling pathway and PI3K-Akt signaling. Integrated analysis of differentially expressed genes and differential metabolites indicated that they were significantly enriched in the metabolic processes such as nucleotide metabolism, biosynthesis of cofactors and purine metabolism. In addition, the results showed that most of the detected metabolites involved in the bile secretion was downregulated during TGEV infection. Furthermore, exogenous addition of key metabolite deoxycholic acid (DCA) significantly enhanced TGEV replication by NF-κB and STAT3 signal pathways. CONCLUSIONS: We identified a significant metabolite, DCA, related to TGEV replication. It added TGEV replication in host cells by inhibiting phosphorylation of NF-κB and STAT3. This study provided novel insights into the metabolomic and transcriptomic alterations related to TGEV infection and revealed potential molecular and metabolic targets for the regulation of TGEV infection.

Lycopene Alleviates Deoxynivalenol-induced Toxicity in Porcine Intestinal Epithelial Cells by Mediating Mitochondrial Function.

Deoxynivalenol (DON) is widely found in food and feed, posing a threat to human and animal health. Lycopene (Lyc) is a natural plant extracts with significant antioxidant properties. This study was conducted to investigate the protective effects of Lyc on IPEC-J2 cells upon DON exposure. The detection of cell viability and trypan blue staining showed that Lyc alleviated cell damage and decreased cell apoptotic rate induced by DON. The analysis of reactive oxygen species (ROS) level and antioxidant parameter measurements showed that Lyc significantly down-regulated the content of ROS and restored antioxidant enzyme activity. Furthermore, mitochondrial membrane potential (ΔΨm) detection, mitochondrial DNA copy number (mtDNAcn) assay and adenosine triphosphate (ATP) concentration detection showed Lyc improved mitochondrial function after DON exposure. The results of transcriptome analysis, ROS detection and CCK8 assay suggested that Lyc may activated the oxidative phosphorylation (OXPHOS) to improve mitochondrial function. Conclusively, our results suggested that Lyc alleviated DON-induced oxidative stress by improving mitochondrial function through OXPHOS signaling pathway.

Expression Analysis and the Roles of the Sec1 Gene in Regulating the Composition of Mouse Gut Microbiota.

The Sec1 gene encodes galactose 2-L-fucosyltransferase, whereas expression during development of the Sec1 gene mouse and its effect on the composition of the gut microbiota have rarely been reported. In this study, we examined Sec1 gene expression during mouse development, constructed Sec1 knockout mice, and sequenced their gut microbial composition. It was found that Sec1 was expressed at different stages of mouse development. Sec1 knockout mice have significantly higher intraperitoneal fat accumulation and body weight than wild-type mice. Analysis of gut microbial composition in Sec1 knockout mice revealed that at the phylum level, Bacteroidetes accounted for 68.8%and 68.3% of gut microbial composition in the Sec1-/- and Sec1+/+ groups, respectively, and Firmicutes accounted for 27.1% and 19.7%, respectively; while Firmicutes/Bacteroidetes were significantly higher in Sec1-/- mice than in Sec1+/+ mice (39.4% vs. 28.8%). In verucomicrobia, it was significantly higher in Sec1-/- mice than in Sec1+/+ group mice. At the family level, the dominant bacteria Prevotellaceae, Akkermansiaceae, Bacteroidaceae, and Lacilltobacaceae were found to be significantly reduced in the gut of Sec1-/- mice among Sec1+/+ gut microbes, while Lachnospiraceae, Ruminococcaceae, Rikenellaceae, Helicobacteraceae, and Tannerellaceae were significantly increased. Indicator prediction also revealed the dominant bacteria Akkermansiaceae and Lactobacillaceae in Sec1+/+ gut microorganisms, while the dominant bacteria Rikenellaceae, Marinifilaceae, ClostridialesvadinBB60aceae, Erysipelotrichaceae, Saccharimonadaceae, Clostridiaceae1, and Christensenellaceae in Sec1-/- group. This study revealed that the Sec1 gene was expressed in different tissues at different time periods in mice, and Sec1 knockout mice had significant weight gain, significant abdominal fat accumulation, and significant changes in gut microbial flora abundance and metabolic function, providing a theoretical basis and data support for the study of Sec1 gene function and effects on gut microbiota-related diseases.