Fecal Microbiota Transplantation from Healthy Piglets Ameliorates Intestinal Inflammation in Mice by Modulating Recipient Metabolism

Abstract Fecal Microbiota Transplantation (FMT) has been clinically applied to treat host intestinal inflammation, such as inflammatory bowel disease (IBD). Research in livestock indicates that the gut microbiota of healthy piglets differs from that of diarrheic piglets, playing a crucial role in regulating intestinal immune development. However, the potential of FMT derived from healthy piglets to alleviate intestinal inflammation in recipients and the underlying mechanisms remain unexplored. This study utilized FMT from healthy piglets to intervene in a dextran sulfate sodium (DSS)-induced intestinal inflammation model in germ-free Kunming (KM) mice, investigating its effects on intestinal barrier function and inflammatory levels. As anticipated, the results demonstrated that FMT significantly alleviated DSS-induced intestinal inflammation. This was evidenced by reduced weight loss and lower disease activity index (DAI) scores. Furthermore, FMT improved intestinal barrier integrity, maintained homeostasis of host inflammatory cytokines, and markedly attenuated oxidative stress. Untargeted metabolomics analysis further revealed that FMT significantly increased the abundance of multiple anti-inflammatory metabolites, including 3-Methoxytyramine-betaxanthin and Sialorphin. Concurrently, FMT upregulated relevant metabolic pathways, notably Betalain Biosynthesis. Correlation analysis indicated a close association between FMT-elevated anti-inflammatory metabolites (e.g., 3-Methoxytyramine-betaxanthin) and improved markers of intestinal inflammation. This study provides novel insights into the mechanism by which pig-derived gut microbiota alleviates host intestinal inflammation through modulation of host metabolism.