Characteristics of Lactococcus petauri GB97 lysate isolated from porcine feces and its in vitro and in vivo effects on inflammation, intestinal barrier function, and gut microbiota composition in mice

ABSTRACT Weaning in piglet management is important to improve pork production. Controlling gut inflammation and colitis is important in managing growth performance in piglets after weaning. Previously, we found that treatment with a lysate of Lactococcus petauri GB97 (LPL97) from porcine feces alleviated lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Here, we aimed to evaluate the exact role of LPL97 in modulating inflammation, epithelial barrier function, and gut microbiota composition, both in vitro and in vivo, in an experimental dextran sulfate sodium (DSS)-induced colitis mouse model. Compared to control colitis mice, LPL97 inhibited shortening of the colon, percentage body weight reduction, and mucosal damage. Moreover, LPL97 treatment downregulated the serum levels of pro-inflammatory factors and their mRNA expression in colon tissue but increased the levels of anti-inflammatory cytokine. LPL97 also reduced intestinal permeability by increasing the expression levels of tight junction (TJ) proteins in colon tissues. Additionally, 16S rRNA gene analysis demonstrated the effect of LPL97 treatment on DSS-induced inflammation via microbiome changes in the mouse intestine. At the genus level, the relative abundance of Mucispirillum, Intestinimonas, Staphylococcus, and Pseudomonas, which was significantly higher in the DSS-treated group than in the control group, decreased significantly in the LPL97 group compared to that in the DSS group. This study provides evidence that LPL97 can prevent intestinal inflammation and strengthen the integrity of the intestinal barrier by altering the gut microbiota, suggesting its promising potential for prophylaxis and treatment of colitis in pig farming. IMPORTANCE Weaning is a crucial step in piglet management to improve pork production. During the weaning phase, disruption of epithelial barrier function and intestinal inflammation can lead to decreased absorption of nutrients and diarrhea. Therefore, maintaining a healthy intestine, epithelial barrier function, and gut microbiota composition in this crucial phase is strategic for optimal weaning in pigs. We isolated a lysate of Lactococcus petauri GB97 (LPL97) from healthy porcine feces and evaluated its anti-inflammatory activities, barrier integrity, and gut microbial changes in LPS-induced murine macrophages and DSS-induced colitis mice. We found that LPL97 regulated the immune response by downregulating the TLR4/NF-κB/MAPK signaling pathway both in vitro and in vivo. Furthermore, LPL97 alleviated the disruption of intestinal epithelial integrity and gut microbiota dysbiosis in colitis mice. This study indicates that LPL97 has the potential to be developed as an alternative feed additive to antibiotics for the swine industry. Weaning is a crucial step in piglet management to improve pork production. During the weaning phase, disruption of epithelial barrier function and intestinal inflammation can lead to decreased absorption of nutrients and diarrhea. Therefore, maintaining a healthy intestine, epithelial barrier function, and gut microbiota composition in this crucial phase is strategic for optimal weaning in pigs. We isolated a lysate of Lactococcus petauri GB97 (LPL97) from healthy porcine feces and evaluated its anti-inflammatory activities, barrier integrity, and gut microbial changes in LPS-induced murine macrophages and DSS-induced colitis mice. We found that LPL97 regulated the immune response by downregulating the TLR4/NF-κB/MAPK signaling pathway both in vitro and in vivo. Furthermore, LPL97 alleviated the disruption of intestinal epithelial integrity and gut microbiota dysbiosis in colitis mice. This study indicates that LPL97 has the potential to be developed as an alternative feed additive to antibiotics for the swine industry.