The Mean of Milk: A Review of Human Milk Oligosaccharide Concentrations throughout Lactation

Abstract

Human milk oligosaccharides (HMOs) are non-digestible and structurally diverse complex carbohydrates that are highly abundant in human milk. To date, more than 200 different HMO structures have been identified. Their concentrations in human milk vary according to various factors such as lactation period, mother’s genetic secretor status, and length of gestation (term or preterm). The objective of this review is to assess and rank HMO concentrations from healthy mothers throughout lactation at a global level. To this aim, published data from pooled (secretor and non-secretor) human milk samples were used. When samples were reported as secretor or non-secretor, means were converted to a pooled level, using the reported mean of approximately 80/20% secretor/non-secretor frequency in the global population. This approach provides an estimate of HMO concentrations in the milk of an average, healthy mother independent of secretor status. Mean concentrations of HMOs were extracted and categorized by pre-defined lactation periods of colostrum (0–5 days), transitional milk (6–14 days), mature milk (15–90 days), and late milk (>90 days). Further categorizations were made by gestational length at birth, mother’s ethnicity, and analytical methodology. Data were excluded if they were from preterm milk, unknown sample size and mothers with any known disease status. A total of 57 peer-reviewed articles reporting individual HMO concentrations published between 1996 and 2020 were included in the review. Pooled HMO means reported from 31 countries were analyzed. In addition to individual HMO concentrations, 12 articles reporting total HMO concentrations were also analyzed as a basis for relative HMO abundance. Total HMOs were found as 17.7 g/L in colostrum, 13.3 g/L in transitional milk, and 11.3 g/L in mature milk. The results show that HMO concentrations differ largely for each individual HMO and vary with lactation stages. For instance, while 2′-FL significantly decreased from colostrum (3.18 g/L ± 0.9) to late milk (1.64 g/L ± 0.67), 3-FL showed a significant increase from colostrum (0.37 g/L ± 0.1) to late milk (0.92 g/L ± 0.5). Although pooled human milk contains a diverse HMO profile with more than 200 structures identified, the top 10 individual HMOs make up over 70% of total HMO concentration. In mature pooled human milk, the top 15 HMOs in decreasing order of magnitude are 2′-FL, LNDFH-I (DFLNT), LNFP-I, LNFP-II, LNT, 3-FL, 6′-SL, DSLNT, LNnT, DFL (LDFT), FDS-LNH, LNFP-III, 3′-SL, LST c, and TF-LNH.

Safety of 3’‐sialyllactose (3’‐SL) sodium salt produced by derivative strains of Escherichia coli BL21 (DE3) as a Novel Food pursuant to Regulation (EU) 2015/2283

“…As reported in previous EFSA opinions (EFSA NDA Panel, 2019b, 2020a,b, 2021, human milk contains a family of structurally related oligosaccharides, known as HMOs, which is the third largest fraction of solid components. The highest concentrations of HMOs occur in human colostrum (20-25 g/L), and concentrations between 5 and 20 g/L occur in mature human milk (Thurl et al, 2010;Bode, 2012;Urashima et al, 2018).…”

“…Table 4: Estimated daily intake levels of 3'-SL from average (800 mL) and high (1,200 mL) human milk intakes for infants of 6.7 kg bw, based on mean and high concentrations of 3'-SL of 0.19 g/L and 0.70 g/L, respectively, in mature human milk (Soyyılmaz et al, 2021) Daily intake levels (mg/kg bw) from 800 mL of human milk Daily intake levels (mg/kg bw) from 1,200 mL of human milk…”

In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis

“…A review of HMO concentrations in mature human milk, pooled from 57 studies published between 1966 and 2020, identified the 15 oligosaccharides that were in greatest abundance [54]. All 15 HMOs were predicted within the model, and a biosynthetic network was constructed (Supplementary Figure S1), in which all of the enzymes except the cIGnT activity (10) were used.…”

Human Milk Oligosaccharides: A Comprehensive Review towards Metabolomics

“…The most abundant HMOs include the 2′-fucosyllactose (2′-FL) which belongs to the fucosylated group. Lacto- N -tetraose (LNT) has been recently demonstrated to be the second most abundant HMO [ 27 ]. Others include the Lacto- N -neotetraose (LNnT), which belong to the neutral non-fucosylated [ 28 ].…”