In vitro faecal fermentation metabolites of 2′-fucosyllactose protect against intestinal epithelial injury: Infant enterotype effects

In this study, we conducted in vitro fermentation with infant faecal inocula dominated by Bifidobacterium longum, Bifidobacterium breve, and Bacteroides enterotypes, and assessed the efficacy of the metabolome associated with 2′-fucosyllactose (2′-FL) fermentation on lipopolysaccharide-induced epithelial cell barrier damage on Caco-2 cells. The results revealed that propionate and butyrate were more prominent in the Bacteroides-dominated group, whereas the Bifidobacterium-dominated group was associated with an increased molar fraction of lactate (∼16 mM). Additionally, our study demonstrated that 2′-FL faecal metabolites (FMs) decreased the production of inflammatory cytokines, and promoted tight junction gene expression by inhibiting the TLR4/NF-κB/MLCK signalling pathway and activating the Nrf2/HO-1 pathway. The 2′-FL FMs from Bacteroides-dominated enterotypes had a unique advantage in regulating the TLR4/NF-κB/MLCK signalling pathway, which can be attributed to the effects of propionate and butyrate.