Table 3.

Evidence supporting roles of hMOS in mucosal signaling and epithelial protection.

HMOS	Targets/Models	Mucosal Signaling Effects	References
Acidic	Intestine; NEC model rat	Attenuate TLR4/NF-κB/NLRP3-mediated inflammation and suppress inflammatory signals of IL-1β, IL-6, TNFα to prevent NEC development	[96]
Mixture (human colostrum isolates)	Immature intestinal tissue; aborted fetuses	Attenuate pathogen-associated molecular pattern-stimulated IL-1β, IL-6, IL-8, MCP-1 expression while promoting MIP-1-δ, MIP-1-β, TIMP-2 and PDGF the mediators of tissue repair	[86]
Mixture (human milk isolates)	Intestinal epithelial cells in vitro; human	Suppress TNFα and IL-1β induced inflammtory signals of IL-8, MIP-3α and MCP-1	[91]
	Intestinal epithelial cells in vitro; human	Enhance epithelial differentiation and promote alkaline phosphatase activity	[88]
2′FL	Intestinal cells; human, mice, pigs	Attenuate CD14 expression and suppress LPS-induced IL-8 production in ETEC exposed intestinal cells	[87]
	Intestinal epithelial cells in vitro; human	Suppress Campylobactor jejuni-induced mucosal inflammatory signals of IL-1β, IL-8, MIP-2	[94]
	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.