Human milk oligosaccharides tied to infant growth

Levels of several human milk oligosaccharides (HMOs), such as 2’-fucosyllactose (2’FL) and lacto-N-tetraose (LNT), appear to correlate with measures of growth in breastfed infants, according to a recent Philippine study.

Twenty-four different HMOs were measured in 41 mother-infant dyads, from 0.75 through 4 months of infant age. The concentrations of most HMOs declined steadily through the first 4 months of age, except for three that remained relatively constant: alpha-tetrasaccharide (A-tetra), lactodifucotetraose (LDFT), and lacto-N-neodifucohexaose (LNnDFH). [Sci Rep 2022;12:17304]

Meanwhile, 3’-galactosyllactose (3’GL) levels were hardly detectable, while 6’-galactosyllactose (6’GL) and 3-fucosyllactose (3FL) increased over time.

Seven HMOs were found to be significantly associated with growth parameters. Of these, LDFT, LNnDFH, 2’FL, 6’GL, and lacto-N-difucohexaose-I (LNDFH-I) were positively associated with at least one growth parameter. In contrast, monofucosyllacto-N-hexaose-III (MFNLH-III) and 3FL showed an inverse interaction with growth metrics.

For example, head circumference and head circumference-for-age z-score at 6 months were associated with greater areas under the curve (AUC) for LDFT, LNDFH-I, and LNnDFH for the first 4 months of lactation. Additionally, the AUC for LNnDFH over this lactation time span was also positively associated with length and length-for-age z-score at 6 months of infant age.

For 2’FL, AUC over the first 4 months of lactation correlated significantly with length gain and length gain-for-age z-score through 6 months of age. A similar interaction was reported between 6’GL and weight gain and weight-gain-for age z-score.

Meanwhile, AUC for 3FL through the first 4 lactation months was tied with slower length gain and length gain-for-age z-score through 6 months of infant age.

Similarly, MFLNH-III AUC during the first 4 months was inversely associated with head circumference and head circumference-for-age z-score, weight and weight-for-age z-score, length and length-for-age z-score, and length gain and length gain-for-age z-score through the first 6 months of growth.

“For the first time, we report here the concentration of 24 structurally distinct HMOs measured longitudinally over the first 4 months of lactation in a cohort of Filipino mothers and their exclusively breastfed infants,” the researchers said.

“Although this cohort was relatively small, our exploratory analysis revealed indications of a possible relation between specific HMOs in breastmilk and exclusively breastfed infant growth measures, mainly head circumference and body length,” they added.

Of note, most of the obtained interactions, though statistically significant, were weak in magnitude, indicating the need for caution when extrapolating to other mother-infant populations and for future analyses in this context.

The study included enrolled 41 mother-infant dyads for a prospective and observational analysis of HMO profile. Only those with healthy, term, and singleton births were eligible. All infants were exclusively breastfed and would have been so for up to 6 months of age. Those with major congenital malformations, significant pre- or postnatal disease, and admitted to the neonatal intensive care unit were excluded.

“These findings may be especially relevant in Asian populations such as the Filipino infants examined herein where growth often tends to be closer to the lower end of the [World Health Organization] reference range and infants are more likely to experience growth faltering,” the researchers said.

“Future research should confirm these associations in diverse populations, including those with some degree of under- or malnutrition, and with longer follow-up periods,” they added.

Assessments of gut microbiota and digestive health would also be valuable to elucidate mechanisms by which HMO profiles affect growth, according to the researchers.