Faecal Microbiota Transplantation Reduces Susceptibility to Epithelial Injury and Modulates Tryptophan Metabolism of the Microbial Community in a Piglet Model

Faecal microbiota transplantation [FMT] has shown promise as a treatment for inflammatory bowel disease [IBD]. Using a piglet model, our previous study indicated that exogenous faecal microbiota can increase the expressions of tight junction proteins, mucin and antimicrobial peptide in the intestinal mucosa, suggesting a beneficial effect of FMT on gut barrier and gastrointestinal health. However, specific connections between FMT-induced microbial changes and modulation of the intestinal barrier remain to be fully illustrated. Here, we aimed to determine the potential role of metabolic function of gut microbiota in the beneficial effects of FMT. The influence of FMT on the maintenance of intestinal homeostasis was assessed by early-life gut microbiota intervention on newborn piglets and subsequent lipopolysaccharide [LPS] challenge. Analysis of the gut microbiome and metabolome was carried out by 16S rRNA gene sequencing and multiple mass spectrometry platforms. FMT modulated the diversity and composition of colonic microbiota and reduced the susceptibility to LPS-induced destruction of epithelial integrity and severe inflammatory response. Metabolomic analysis revealed functional changes of the gut metabolome along with a significant increase of the typical microbiota-derived tryptophan catabolite indole-3-acetic acid in the colonic lumen. In concordance with the metabolome data, metagenomics prediction analysis based on 16S rRNA gene sequencing also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with indole alkaloid biosynthesis, cytochrome P450 and intestinal homeostasis, which coincided with up-regulation of cytokine interleukin-22 and enhanced activation of aryl hydrocarbon receptor in the recipient colon. Our data reveal a regulatory effect of FMT on tryptophan metabolism of gut microbiota in the recipient colon, which may play a potential role in maintenance of the intestinal barrier.