In a recent study published in JAMA Network Open, researchers examine the impact of an exclusive human milk weight-reduction plan on the infant gut microbiome.

Study: Effect of an Exclusive Human Milk Diet on the Gut Microbiome in Preterm Infants: A Randomized Clinical Trial. Image Credit: Iryna Inshyna / Shutterstock.com

Advantages of breast milk

Receipt of a mother’s breastmilk is related to improved metabolic and cognitive outcomes, in addition to reduced neonatal morbidity rates in preterm infants. Nonetheless, a shortfall in supply necessitates using pasteurized human milk or bovine formula.

There stays a scarcity of randomized clinical trials (RCTs) which have determined the optimal complement for infants when the mother’s milk supply is insufficient. One previous meta-analysis reported reduced necrotizing enterocolitis (NEC) rates in infants exclusively fed human donor milk in comparison with formula-fed infants. Nonetheless, this difference was insignificant in studies when formula was only used as to complement.

A number of the different mechanisms by which breast milk might reduce the chance of NEC include the dearth of bovine antigens inside breast milk which will cause a response within the infant. As well as, the presence of specific functional components inside breast milk, resembling lactoferrin and human milk oligosaccharides (HMOs), may additionally exert certain helpful effects on the gut microbiota.

In regards to the study

In the current RCT, researchers determine the effect of an exclusive human milk weight-reduction plan on the gut microbiome in preterm infants. Herein, preterm infants from 4 NICUs within the U.K. were recruited for inclusion within the study inside 72 hours of life who had only received moms’ breastmilk. Infants with congenital and life-threatening conditions were excluded.

Infants were randomized to intervention (exclusive human milk weight-reduction plan) and control (standard weight-reduction plan) arms. Feeding within the control arm included using the mother’s breastmilk and preterm formula milk to compensate for the shortfall in breastmilk supply. Infants within the intervention arm were fed breastmilk and a pasteurized human milk product to make up for the breastmilk shortfall.

Control group infants received a bovine-derived fortifier, whereas those within the intervention arm received a human milk-derived fortifier. Infants continued to receive their assigned diets until 34 weeks post-menstrual age (PMA).

Morbidity and weight gain data were obtained until discharge. Then, data on demographics and outcomes were captured using medical records and the National Neonatal Research Database.

Stool samples were collected every day and analyzed at baseline, the tenth day of life (DOL), full feeds, DOL 21-28, and the ultimate sample at 34 weeks’ PMA. Stool samples were subjected to DNA extraction and sequencing, V4 16S rRNA sequencing, in addition to evaluation of Shannon diversity and bacterial richness. Multiple cross-sectional analyses were performed to discover covariates related to metagenomic profiles.

Findings

The team recruited 126 preterm infants from September 2017 to September 2019. Sixty-three infants were randomized to the control group and the remaining to the intervention arm.

Eighty-six infants were born before 28 gestational weeks. 4 infant deaths amongst controls and eight from the intervention arm were recorded at a median post-natal age of 25 and 15 days, respectively.

Ready-to-feed human or formula milk represented lower than 1% of fluid intake in infants who died. Although surgical NEC affected one infant from each cohort, NEC was not the first reason for death.

The team analyzed 472 stool samples from 116 subjects. First, the authors observed a big association between the NICU site and probiotic use with bacterial profiles. The trial group (control or intervention) was not related to bacterial profiles at any time.

Generalized linear mixed models revealed that trial groups weren’t related to bacterial richness or Shannon diversity differences. Nonetheless, evaluation of ultimate stool samples showed that Shannon diversity and richness were related to the trial group. Corynebacterium and Staphylococcus negatively correlated with DOL, whereas Veillonella, Escherichia, Enterobacter, Bifidobacterium, and Clostridium showed positive correlations.

Moreover, the relative abundance of Bifidobacterium in infants from NICUs using probiotics was higher. Moreover, Bifidobacterium abundance was negatively correlated with the variety of days on antibiotics and positively correlated with the variety of days on moms’ milk. The intervention arm was significantly related to a lower relative abundance of Lactobacillus.

Conclusions

The present study investigated the effect of an exclusive human milk weight-reduction plan on the infant gut microbiome. The researchers found no effect of the trial group on Shannon diversity or microbial richness; nonetheless, infants within the intervention arm had different microbiome profiles that weren’t replicated in weighted analyses. Thus, an exclusive human milk weight-reduction plan affected taxa like Lactobacillus with low abundance, which was lower in intervention group infants.

Journal reference:

• Embleton, N. D., Sproat, T., Uthaya, S., et al. (2023). Effect of an Exclusive Human Milk Diet on the Gut Microbiome in Preterm Infants: A Randomized Clinical Trial. JAMA Network Open 6(3):e231165. doi:10.1001/jamanetworkopen.2023.1165