Lacto-N-neotetraose (LNnT, Galβ1-4GlcNAcβ1-3Galβ1-4Glc) ranks as the #2 neutral human milk oligosaccharide after 2′-FL, comprising 8-12% of total HMOs in mature breast milk and appearing as a white hygroscopic powder essential for Bifidobacterium-selective gut colonization and infant barrier function. This type 2 chain tetrasaccharide serves as universal precursor for Lewis X (LNFP III), sialyl-Lewis X, and difucosyl HMOs, demonstrating 3-5x Bifidobacterium bifidum/longum growth stimulation versus glucose while resisting Bacteroides/Clostridium hydrolysis; commercially scalable via engineered E. coli β4GalT1/β3GnT2 (>99% purity, FDA/EFSA GRAS), it inhibits ETEC/rotavirus adhesion 75-90% through competitive receptor mimicry, upregulates tight junctions (ZO-1↑2x/claudin↑1.5x), reduces NEC risk 45-65% via TLR4/NOD2 modulation, supports hippocampal neurogenesis through ganglioside mimicry, and exhibits gastric stability pH 2.5-9 with >800 g/L solubility and 60-month shelf life ideal for infant formula fortification up to 1.5 g/L.
Appearance
White to off-white amorphous hygroscopic powder.
Ultra-high water solubility >800 g/L; clear solutions pH 6-8.
Source
8-12% total HMOs mature human milk; 4-6% colostrum.
Microbial fermentation: β4GalT1/β3GnT2 engineered E. coli.
Molecular Weight and Structure
707.63 g/mol, formula C₂₆H₄₅NO₂₁ (CAS 13007-32-4).
Galβ1-4GlcNAcβ1-3Galβ1-4Glc type 2 chain tetrasaccharide.
Sugar Specificity
B. bifidum/longum β3GnTase/β4GalTase (Km 0.2-0.8 mM).