Inhibitory effect of gut microbiota-fermented trisaccharide GuFGa (Glc-Fuc-Gal) on Campylobacter jejuni: insights from transcriptomic and metabolomic analyses

Abstract

Fucose-rich carbohydrates, such as 2'-fucosyllactose and fucoidan, are recognized as anti-infective components that protect the host from pathogens. In this study, the response of the common enteric pathogen Campylobacter jejuni to a specific fucose-containing trisaccharide (GuFGa, β-D-Glcp-(1 → 4)-[β-D-Galp-(1 → 3)]-α-ʟ-Fucp) fermented with human fecal microbiota was investigated using metabolomic and transcriptomic analyses. The protective effect of GuFGa-derived microbial metabolites against C. jejuni was assessed in vitro using a cell-based model. No directly inhibitory effect of GuFGa was observed with the growth of C. jejuni during single-strain cultivation. However, the supernatant of GuFGa fermented with human fecal microbiota (F-GuFGa) reduced the relative abundance of C. jejuni by tenfold within the microbial community. Transcriptome data showed that 128 differentially expressed genes of C. jejuni induced by F-GuFGa treatment were mainly enriched in oxidative phosphorylation and bacterial secretion systems (type IV). Fecal fermentation of GuFGa altered 452 differentially abundant metabolites, which were mainly enriched in phenylalanine and tryptophan metabolism. Correlation analysis indicated that the expression of type IV secretion system genes was significantly negatively correlated with the abundance of phenylacetic acid (PAA) and D-3-phenyllactic acid (D-PLA) (P < 0.05). Adhesion of C. jejuni to Caco-2 cells was reduced by treatment with F-GuFGa, PAA and D-PLA, with the highest inhibition rate observed for F-GuFGa (44.4%), followed by D-PLA (33.3%). This study provides a new perspective for developing GuFGa and similarly fucose-rich oligosaccharides as innovative dietary interventions to inhibit bacterial infections and improve gut health.

Keywords

Fucose-rich oligosaccharide / Gut microbiota / Campylobacter jejuni / Aromatic acid / In vitro fermentation / Caco-2 cell

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