In a substantial development in understanding the role of breast milk and immunity in babies, Chinese researchers demonstrated for the first time that some proteins, including casein found in breast milk, promote the development of microbiota in the guts of babies, thereby indirectly influencing the immunity-regulating activity of breast milk proteins.

In the study recently published in Frontiers in Microbiology, the scientists demonstrated that variation in the protein content of breast milk between women explains much of the variance in the abundance of essential beneficial microorganisms in their guts, implying that these proteins play a regulatory role in the immunological function of the gut microbiome in humans.

Breast milk has evolved over 320 million years to suit all of the physiological demands of babies, containing not just nutrients but also hormones, antimicrobials, digestive enzymes, and growth factors.

Furthermore, numerous preclinical studies have found that proteins included in breast milk, including casein and milk fat globule membrane proteins, not only provide energy and molecular building blocks but also directly promote immunity, the researchers said.

Likewise, because of their position in the gut microbiota, breast milk proteins may have a dual immune-boosting function, directly stimulating the immune system and indirectly influencing the number of gut microorganisms, which in turn, influence immunity.

Commenting on the findings of the study, joint senior author Dr Ignatius Man-Yau Szeto from the Yili Maternal and Infant Nutrition Institute in Beijing said, "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 and necessary for health."

"These findings suggest that maternal proteins play a role in the early immune and metabolic development of immunity in babies," he added.

For their study, Dr Szeto and his team looked at the protein composition of 23 Chinese mothers as well as the diversity and number of beneficial gut microorganisms in their infants' faeces using liquid chromatography techniques.

Focusing on nine proteins found in breast milk, the researchers found that casein, alpha-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 after delivery.

They further found that the bacterial species Bifidobacterium, Escherichia coli, Streptococcus, and Enterobacter dominated the gut microbiome of the newborns.

Explaining their work, Co-senior author Dr Ai Zhao from Tsinghua University said, "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 have not yet been fully discovered, so we wanted to examine their potential role in regulating the microbiome of infants," Dr Zhao added.

The strongest associations were discovered between breast milk protein concentrations and two beneficial bacteria that were relatively rare within the guts of babies' microbiome, namely Clostridium butyricum and Parabacteroides distasonis, both of which are used as probiotics for humans and domestic animals.

"The results of this study suggest that specific proteins in breast milk can influence the abundance of certain gut microbes in infants, playing a significant role in early immune and metabolic development," the authors concluded.

Pointing out that further studies are necessary to substantiate their findings, Dr Szeto said, "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," he added.