Pectin modulates intestinal immunity in a pig model via regulating the gut microbiota-derived tryptophan metabolite-AhR-IL22 pathway.

ABSTRACT

BACKGROUND: Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator, promoting intestinal development and regulating intestinal flora in the gut. However, the relevant mechanisms remain obscure. In this study, pigs were fed a corn-soybean meal-based diet supplemented with either 5% microcrystalline cellulose (MCC) or 5% pectin for 3 weeks, to investigate the metabolites and anti-inflammatory properties of the jejunum. RESULT: The results showed that dietary pectin supplementation improved intestinal integrity (Claudin-1, Occludin) and inflammatory response [interleukin (IL)-10], and the expression of proinflammatory cytokines (IL-1ß, IL-6, IL-8, TNF-α) was down-regulated in the jejunum. Moreover, pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets. Pectin specifically increased the abundance of Lactococcus, Enterococcus, and the microbiota-derived metabolites (skatole (ST), 3-indoleacetic acid (IAA), 3-indolepropionic acid (IPA), 5-hydroxyindole-3-acetic acid (HIAA), and tryptamine (Tpm)), which activated the aryl hydrocarbon receptor (AhR) pathway. AhR activation modulates IL-22 and its downstream pathways. Correlation analysis revealed the potential relationship between metabolites and intestinal morphology, intestinal gene expression, and cytokine levels. CONCLUSION: In conclusion, these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway, which is activated through tryptophan metabolites.