2′-Fucosyllactose impacts the expression of mucus-related genes in goblet cells and maintains barrier function of gut epithelial cells

High-Level De Novo Biosynthesis of 2′-Fucosyllactose by Metabolically Engineered Escherichia coli

“…1 The health benefits of 2′-FL have been thoroughly investigated and confirmed, especially for infants, including prebiotic effect, 2 immune modulators, 3 and maintaining barrier function of gut epithelial cells. 4 The safety evaluation and clinical trials of 2′-FL have widely been studied, and it is suggested that 2′-FLcontaining infant formula is safe and well-tolerant for infants. 5 2′-FL has been approved as Generally Recognized As Safe (GRAS) by American Food and Drug Administration (FDA) and commercially added to infant formula.…”

“…Among more than 200 HMOs, 2′-fucosyllactose (2′-FL) is the most representative one and constitutes the essential component accounting for up to approximately 30% (w/w) of total HMOs . The health benefits of 2′-FL have been thoroughly investigated and confirmed, especially for infants, including prebiotic effect, immune modulators, and maintaining barrier function of gut epithelial cells . The safety evaluation and clinical trials of 2′-FL have widely been studied, and it is suggested that 2′-FL-containing infant formula is safe and well-tolerant for infants .…”

Diet, microbiota, and the mucus layer: The guardians of our health

“…Human milk oligosaccharides (HMOs) which are the most abundant components in breast milk cannot be digested by the human infant, but because of their structural similarity to mucin-glycans, they can be used as a primary carbon source by several bacterial strains (e.g., Bifidobacterium species, members from the genus Bacteroides ) implicated in the initial colonization of our intestine, with beneficial effect on our mucosal, immune, and metabolic health during later life ( 163 , 164 ). Both in vitro and in vivo studies have highlighted the ability of HMOs and HMO-compounds (i.e., 2′ -fucosyllactose) to modulate mucins expression and the secretory function of GCs ( 165 , 166 ). HMOs can directly control intestinal immunity by decoying receptors of pathogenic bacteria and viruses, thereby preventing their binding on intestinal cells and the onset of a disease ( 167 ).…”

Human Milk Oligosaccharides: Potential Applications in COVID-19

“…Furthermore, 2 FL can attenuate the expression of CD14, the co-receptor of TLR4 [87], thus supporting its antagonistic effects against TLR4-mediated mucosal inflammation. Intestinal epithelial cells in vitro; human, mice Suppress TLR4 expression and TLR4-mediated NF-κB signaling to prevent intestinal inflammation and NEC development [95] Intestinal epithelial cells in vitro; human Selectively inhibit CCL20 release from Ag-IgE complex stimulated intestinal cells in a PPARγ independent manner [97] Intestinal epithelial cells in vitro; human Induce upregulation of DEFB1 and ZO-1 genes under the peristalsis-mimic shear force and promote tight junction formation [98] Goblet cells in vitro; human Induce upregulations of mucus associated genes TFF3 and CHST5 and promote the mucus barrier function [90] Intestinal epithelial cells in vitro; human Modulate glycosylation genes of galectin and downregulate ICAM-1 to prevent pathogen adhesion [93] 3 SL Intestine; IL-10(-/-) colitis mice Promote colitis severity and modulated mucosal immunity by stimulating CD11c + dendritic cells through TLR4 pathway [70] Intestinal epithelial cells in vitro; human Induce upregulation of DEFB1 and ZO-1 genes under the peristalsis-mimic shear force and promote tight junction formation [98] 6 SL Intestinal epithelial cells in vitro Inhibit chemokine (IL-8 and CCL20) release from Ag-IgE complex stimulated intestinal cells [97] Intestine; human, mice, pigs Suppress TLR4 expression and TLR4 signaling to prevent NEC development [95] DSLNT Intestine; NEC model rat Attenuate mucosal inflammation by a selectin-independent process to prevent NEC development [99] Abbreviations: DEFB1, defensin β-1; DSLNT, disialyllacto-N-tetraose; ETEC, enterotoxigenic E. coli; MCP1, monocyte chemoattractant protein 1; MIP, macrophage inflammatory protein; NEC, necrotizing enterocolitis; NF-κB, nuclear transcription factor-κB; PDGF, platelet-derived growth factor; TFF3, trefoil factor 3; TIMP-2, tissue inhibitor of metalloproteinase-2; TJP-1, Tight junction protein-1; ZO-1, zonula occludens-1.…”

“…HMOS are known to modulate mucosal signaling cascades including TLR4 ( Table 3 ). HMOS alter gene expression in the intestinal epithelial cells which promote intestinal cell maturation, mucosal barrier function, tissue repair and tight junction integrity while attenuating LPS-induced inflammation through suppressing TLR4 signaling [ 86 , 87 , 88 , 89 , 90 ]. HMOS isolated from colostrum could directly modulate mucosal inflammatory signaling of immature human intestinal tissue by attenuating the expression of proinflammatory cytokines (i.e., IL-1β, IL-6, IL-8, and TNFα) [ 86 , 91 ].…”