When I stumbled into human milk research during my PhD, part of my wonder at the subject was how little I had known during medical and paediatric training about the constituents of human milk. Like many medics, and two-thirds of the UK population, I had assumed that infant formula was biochemically so similar to mother’s milk that there was little difference in development and long-term health caused by how a baby was fed.
Realising the truth has been somewhat like Alice falling down the rabbit hole.
Human milk is alive. It changes with the time of day, seasons, potentially even the sex of the child. As a living fluid, it contains stem cells from the mother’s breast tissue, which are absorbed by the baby’s gut and find their way into many of their organs. We don’t as yet know their function, or whether it is simply a consequence of the huge increase in breast stem cell populations during pregnancy and early lactation.
Human milk contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. My work at Imperial College is starting to look at milk in intense detail, understanding how it changes over a normal course of lactation (at least two years), and how those changes could lead to the personalisation of donor milk provision for very sick babies in hospital neonatal units. Breastfeeding also has a significant impact on the mother’s physiology, and yet very little science has examined how this happens.
Furthermore, the impact of mother’s milk on the developing immune system is starting to come to light. How the immune system works and interacts with the microbiome of each organ, is now recognised as a principal driver of health. Rather than just being the response to infections, inflammation may underpin cancer, cardiovascular disease, mental health conditions, autoimmune disease, and dementias. A range of maternal immune cells find their way into milk, bolstering the baby’s developing immune system, protecting them directly from pathogens, and helping to train the infant’s immunity to recognise friendly bacteria from harmful ones.
Milk is more than just antibodies.
The infant gut evolved to expect to digest human milk – and it is a critical interface between the environment and the immune system. When a baby is born, the number of immune tools they possess is relatively small – they are immunocompromised. The lining of their gut is designed to allow two-way communication in the earliest weeks, and this communication seems to help train the immune system to recognise bacterial friends from foe. Infant dendritic cells just beneath the lining of the intestine poke tendrils through into the lumen, sampling the bacteria within the gut that are passengers in milk. They chop up these bacterial proteins and present them to other types of immune cells, which then remember potential threats for a lifetime. When solid food, or anything that is not human milk, is ingested, the lining of the gut closes up, blunting this sampling process. When babies start taking solids, this is a neat way to ‘seal’ the gut lining – nobody wants a chunk of cucumber in their gut tissue. However, the gut lining does not differentiate between the infant starting to take sticks of cucumber or purees at six months or formula with cow milk protein at one week. The closure is irreversible, meaning theoretically, a baby’s immune system is stunted. The effect is greater the earlier and higher the intervention with formula, or anything else that is not human milk.
Recent findings have shown that human milk components may also protect children from obesity. Child obesity is increasing rapidly globally and brings an increased risk of adult obesity and related diseases (type II diabetes, hypertension, and heart disease, amongst others). Risk factors for obesity in childhood are complex, including parental health before conception, during pregnancy and the age and type of weaning. However, recent results from the prospective, large cohort CHILD study in Canada showed that babies who are not breastfed have an increased risk of being overweight by the age of one year. While studies had hinted at this earlier, the effect was thought to be explained by inadvertent overfeeding when using bottles and infant formulas having higher protein levels than human milk. A few months ago, scientists published a remarkable new mechanism, and it all comes down to a small group of fatty acids, almost unique to human milk.
Humans contain broadly two types of fat cells – those that store energy (white fat or white adipose tissue [WAT]) and those that create heat (‘thermogenic’ brown [BAT] or beige fat cells [BeAT]). Thermogenic fat cells help babies and infants to maintain their body temperature without shivering. They produce 300 times more heat than any other tissue! Beige fat cells are found in humans in the neck, along the spine, in the skin of the abdomen and the armpit. Most BeAT cells will convert into energy-storing white fat during late infancy and teenage years, but some remain tucked away in fatty tissue in adults, surrounded by white fat. When adults live in extremely cold conditions or develop diseases like cancer that causes rapid weight loss, white fat cells can convert into BeAT cells to produce heat. Interestingly, the presence of BeAT cells also helps sugar metabolism, reducing levels of insulin sensitivity seen in type II diabetes. Making sure BeAT cells are around for as long as possible in childhood may be a way to combat obesity. The authors of this new study show using a number of techniques that certain fats found only in human milk stop BeAT cells converting into WAT in babies and young infants. These fats (alkylglycerol ether lipids, AKGs) are not found in infant formula or adult diets. Feeding to one year seems to preserve BeAT cells to adolescence.
There is no doubt that the complexity of breast milk is not just the sum of its parts, but the inter-relationship between each constituent, and is influenced by the needs and environment of the child and the mother. The key is the soup, not the ingredients, and this could never be replicated. Not every component is even known yet, and not every one of the molecules that are known, are understood, let alone their function in the unique environment of each mother and child’s microbiome, metabolome and epigenome.
But there is even more going on here – potentially even communication between the baby and the mother before they can talk on a fundamental level. Anecdotally, mothers share pictures of their expressed milk before and after a child becomes ill – the colour clearly changes. What might be the mechanism? One idea is that during suckling, the vacuum created allows a small amount of saliva to be sucked back into the breast ducts, presumably carrying a range of signalling molecules, viruses, and bacteria. A sample of the baby’s oral health. Also, there will be messenger molecules called microRNAs, which are short lengths of RNA designed to stick onto parts of the genome and affect gene expression. Exactly how these molecules work in the breast to alter the composition of the milk is not known, but the baby could literally be ordering their next meal with every feed.
Mothers want to breastfeed – over 85% will say so during pregnancy, and it is an instinct probably driven in utero by the developing foetus as a survival mechanism that literally changes women’s brains. The UK has some of the lowest breastfeeding rates in the world, and supplying all the science in the world will not help unless the right support is in place. As new mothers, we have largely lost the skills and cultural awareness of how to breastfeed, position a baby, be looked after, and supported over those critical first few days. With cuts to lactation support services, mothers are now largely reliant on volunteer services to fill in the gaps. The UK has not invested in a national milk bank service, which would ensure the most vulnerable, premature babies have assured access to screened donor milk while mothers are recovering from birth or illness. And there will always be mothers who cannot breastfeed through cancer, the need to take medication that prevents breastfeeding, or other reasons where breasts just don’t work. These families need support too, and access to donor milk, if they wish.
I hope to be able to share more insights into the remarkable science of human milk over the years to come, and through our work at the Human Milk Foundation and the Hearts Milk Bank, ensure that many more babies are able to receive human milk.
Dr Natalie Shenker
UKRI Future Leaders Fellow, Imperial College
Cofounder: The Human Milk Foundation, Hearts Milk Bank