Guifu Decoction Orchestrates Gut Homeostasis and Inhibits PCV2-Induced Inflammation and Enteritis via the PPAR-γ/NF-κB Signaling Pathway

Abstract Background PCV2 infection in piglets reduces growth performance and increases mortality, causing serious economic losses. Guifu decoction (GFD) is a restorative Chinese medical formulation containing several individual herbs with antiviral and anti-inflammatory effects. Animal studies have revealed that GFD is protective in pigs infected with porcine circovirus (PCV2). However, the mechanism is still unclear. In this study, we aimed to evaluate the effects of GFD against PCV2 infection in mice and determine its mechanism of action, focusing on the PPAR-γ/NF-κB signaling pathway. Methods The therapeutic effect of GFD on PCV2-infected mice was assessed in terms of its prevention of ileum and lung pathology. RNA sequencing (RNA-seq) was used to determine pulmonary transcriptome profiles under various conditions. 16S rRNA sequencing was carried out to verify the role of GFD in the regulation of intestinal microbiota. Results We found that GFD treatment reduced the PCV2-induced inflammatory response and damage to the ileum. GFD strengthened the intestinal mucosal barrier and increased the expression of MUC2 mRNA. PCV2 infection reduced the diversity of intestinal microbiota, but GFD treatment increased the relative abundance of lactobacilli and decreased potentially pathogenic bacteria such as Mycoplasma. KEGG enrichment analysis of differentially-expressed genes showed activation of the PPAR-γ/NF-κB pathways; specifically, the expression of Olr1 and Scd1 genes was significantly up-regulated, while Acox2, Plin1, and Cyp4a12b genes were down-regulated. GFD treatment increased PPAR-γ protein and decreased levels of IκBα and P-IκBα, p65 and P-p65 in the PCV2-infected mouse model. Conclusions Taken together, these results indicate that GFD enhanced intestinal integrity and barrier function by altering intestinal microbiota composition, which subsequently alleviated intestinal injury and improved health. It also reduced the systemic response to the virus and subsequent inflammation through the PPAR-γ/NF-κB pathway. Our data provide novel insights into the potential pathophysiology of PCV2-induced disease in piglets and enhance our understanding of the role of the gut microbiota in the mechanism. Deducing how the GFD formulation protects against PCV2 could lead the way to the development of novel effective therapies to combat intestinal diseases and improve the health and growth performance of pigs.