Comparative lipidomic study reveals distinct triacylglycerol composition and molecular species in human milk and...

The structural organization of fatty acids within triacylglycerols (TAGs), particularly at the sn-2 position, determines their metabolic fate. Whether the TAG architecture in human milk, the sole nutrition for infants, is distinct from that in maternal and fetal circulation remains unclear.

We conducted a comparative lipidomic analysis to characterize the molecular and regioisomeric profiles of TAGs across human milk (at 3 lactation stages) and paired maternal/cord plasma.

TAGs from milk (colostrum, transitional, mature; n = 87) and plasma (maternal and cord; n = 58) of 29 mother-infant dyads were analyzed using ultraperformance supercritical fluid chromatography quadrupole time-of-flight mass spectrometry. Regioisomers were quantified via a validated computational model.

Human milk TAGs exhibited a unique compositional and structural profile compared with circulatory TAGs. A key finding was the preferential positioning of docosahexaenoic acid (DHA) at the sn-2 position in major human milk TAGs (e.g., >65% in DHA/O/O), whereas in cord plasma, DHA in analogous TAGs was exclusively at the sn-1/3 positions (P < 0.001). Similarly, palmitic acid (16:0) was predominantly at sn-2 in milk TAGs (>90% in major species) but not in plasma (<35%). Cord plasma was enriched in long-chain polyunsaturated fatty acids (8.2% compared with 2.5% in maternal plasma, P < 0.05; all tests 2-sided) carried by distinct TAG species.

Human milk shows a unique TAG architecture characterized by a conserved sn-2 enrichment of both DHA and palmitic acid, fundamentally different from the TAG regioisomer profiles in maternal-fetal circulation. This sn-2-DHA-rich structure in milk lipids may represent a tailored metabolic design to support neonatal development.