Key Proteins in Human Breast Milk Crucial for Baby’s Healthy Gut

The abundance of two species of bacteria known to be good for human health and used as probiotics, Clostridium butyricum and Parabacteroides distasonis, has been linked to high concentrations of key proteins in human breast milk, particularly osteopontin and κ-casein. These findings imply that proteins in breast milk alter the quantity of advantageous gut microbes in babies, playing a significant role in the early development of the immune system and metabolism.

Breast milk has been modified by more than 320 million years of mammalian evolution to suit all of the physiological requirements of babies; in addition to nutrition, it also includes hormones, antimicrobials, digestive enzymes, and growth factors.

Furthermore, a lot of the proteins found in breast milk, such as casein and the proteins found on milk fat globule membranes, not only serve as energy sources and molecular building blocks but also actively activate immunity, at least in preclinical settings.

Similarly, the gut microbiome, which is made up of bacteria, archaea, and fungi, plays an important role in immune system modulation. This suggests that the immune-boosting action of breast milk proteins could be two-fold: not only through directly activating the immune system but also indirectly by modulating the number of gut microbes, which in turn influences immunity.

A new study published in Frontiers in Microbiology by Chinese researchers provides the first evidence for the latter, indirect, immunity-regulating activity of breast milk proteins.

The scientists demonstrated that variation in the protein content of breast milk in women explains most of the variance in the abundance of essential beneficial microbes in their babies’ guts, indicating that these proteins play a regulatory role in the immune function of the gut microbiome in humans.

Here we show that the concentration of certain proteins in human breast milk predicts the abundance of specific gut microorganisms in infants, which are known to be important necessary for health. These findings suggest that maternal proteins play a role in the early immune and metabolic development of immunity of babies.”

Dr Ignatius Man-Yau Szeto, Study Joint Senior Author, Yili Maternal and Infant Nutrition Institute

Szeto and colleagues looked at the protein composition of 23 Chinese mothers using ultra-performance liquid chromatography-mass spectrometry and the diversity and abundance of beneficial gut microbes in their infants’ stools using rRNA sequencing and quantitative real-time PCR.

Focus on Nine Proteins

We focused on nine milk proteins, including osteopontin, lactalbumin, and κ-casein, because these were recently found to benefit the early development of infants. Their function and mechanisms haven’t yet been fully discovered, so we wanted to examine their potential role in regulating the microbiome of infants.”

Dr Ai Zhao, Study Co-Senior Author, Tsinghua University

Protein concentrations in breast milk were 1.6% 42 days after birth and 1.2% three months later. Casein, α-lactalbumin, and lactoferrin were the most prevalent proteins. Except for immunoglobulin A (an antibody necessary for mucous membrane immune function), the levels of all proteins tested dropped from 42 days to three months post-partum.

The bacterial species Bifidobacterium, Escherichia, Streptococcus, and Enterobacter dominated the gut microbiome of the newborns.

Link to Probiotics

The strongest correlations between the levels of two beneficial bacteria, Clostridium butyricum, and Parabacteroides distasonis, which are both used as probiotics for people and domestic animals, and the concentrations of breast milk proteins were discovered in the gut microbiomes of the infants.

Variation in the concentration of -casein in mothers’ milk, for example, explained most of the variation in the abundance of C. butyricum in their babies’ guts, whereas the change in the concentration of osteopontin explained much of the variance in the abundance of P. distasonis.

The first of these bacteria has been linked to the regulation of gut homeostasis and the prevention of inflammatory bowel disease. The second is intended to combat diabetes, colorectal cancer, and inflammatory bowel disease.

Study authors stated, “The results of this study suggest that specific proteins in breast milk can influence the abundance of certain gut microbes in infants, playing an important role in early immune and metabolic development.”

The authors noted that more research is required.

Szeto concluded, “Our findings are based on correlations, which are not enough to establish a direct causal effect. Future cohort studies and clinical trials, where breast milk or formula is fortified with functional proteins, are needed to prove this.”