Written by: Sandeep Ravindran, Ph.D. | Issue # 74 | 2018
- The first six months of life offer a window of opportunity for preventing allergies, and as a result there’s been a lot of interest in the effects of human milk on allergies.
- A recent review finds that although modulating human milk composition may have the potential to prevent allergies in early life, studies have so far shown conflicting evidence about the protective role of breastfeeding on allergies.
- Breastfeeding is associated with a reduced risk of eczema in the short term but not at 6-7 years of age.
- The conflicting data may be due to variations in study methodologies and outcome measures, as well as heterogeneity in human milk composition.
- Large, standardized studies that account for several constituents of human milk at the same time could help uncover its potential protective effects on allergies.
The past few decades have seen a steady rise in the worldwide prevalence of allergic diseases, which has spurred research aimed at figuring out ways to prevent allergies [1]. The first six months of life are thought to offer a window of opportunity for preventing allergies. “Nowadays, most researchers and clinicians are trying to aim at this window of opportunity,” says Dr. Daniel Munblit of Imperial College London, Sechenov University, and inVIVO Planetary Health.
One area that researchers are focusing on is the effect of breastfeeding on allergy risk [2-4]. “With regards to breast milk, since ideally speaking this should be the only food for the baby in this first six months of life, it seems reasonable to aim at human milk composition to improve it or somehow modify it to reduce the risk of allergic disease development,” notes Munblit.
Human milk is known to be very complex, with variable levels of immune-active molecules, proteins, polyunsaturated fatty acids, oligosaccharides, metabolites, vitamins, and other nutrients and microbial content, and many of these components interact in ways that can affect immunity [5-8]. Breastfeeding is also known to alter the infant gut microbiome and subsequent immune development [8,9]. “It looks like breast milk potentially can have an impact on immunity,” says Munblit. “Overall, I think that breastfeeding is beneficial in a number of ways.”
Interventions that could modify human milk to influence infant immune responses could potentially help reduce the risk of allergies in early life. However, a recent review by Munblit and his colleagues reports that studies have so far shown conflicting evidence about the protective role of breastfeeding on the risk of allergies [10]. The review suggests that the conflicting data may be explained by variations in study methodologies and outcome measures, as well as heterogeneity in human milk composition. Researchers will likely need to conduct more standardized studies that look at human milk as a whole, rather than as individual components, to decipher any potential protective effects of human milk on allergies.
Munblit was a masters student at Imperial College London when he first started looking into the association between human milk and allergic diseases, and he continued to work on this topic during and after his PhD. “My main interest is in the immunological components of human milk,” he says.
Several components of human milk are known to influence immunity and could play a role in reducing the risk of allergies. “Talking about breast milk composition, there are some immunological molecules like TGF-beta and soluble CD14 that can potentially make a difference,” notes Munblit. Milk lipids, particularly polyunsaturated fatty acids such as the omega-3 fatty acids, including docosahexaenoic acid, have also been shown to have anti-inflammatory effects in chronic inflammatory diseases such as asthma [11].
Other components of human milk, such as sugars called oligosaccharides, have been associated with a direct protection against infections and may help reduce the incidence of allergic diseases in breastfed infants later in life [12,13]. Dietary supplementation with specific oligosaccharides has also been shown to reduce the risk of developing allergies in infants [14,15].
Human milk is also known to shape the infant’s gut microbiome, which can influence the risk of non-communicable diseases in later life, including allergies [16-18]. The gut microbiome of children with allergies also differs in composition and diversity from those without allergies [19].
However, despite its known beneficial effects on infant immunity, there is conflicting evidence about the protective role of breastfeeding in relation to the development of allergies. Many studies have tested breastfeeding associations with the onset of allergic sensitization, eczema, and asthma, and the results have been inconsistent.
“With regards to allergic diseases, the results are quite mixed,” says Munblit. “For example, we can see that breastfeeding is associated with a reduced risk of eczema in the short term, but then when you look long term, by six or seven years of age, this effect disappears,” he notes [20,21]. “I don’t know why it happens, maybe there are some additional confounding factors that we don’t take into account,” says Munblit. “There’s still a lot unknown, despite breastfeeding research being embraced for decades, maybe even centuries.”
A systematic review and meta-analysis of eczema research suggests that children under the age of two who were exclusively breastfed for more than 3–4 months were at lower risk of eczema development, but this protective effect was no longer evident after the age of two [20]. Another large observational study assessing more than 200,000 children worldwide reported that breastfeeding offered some protection against severe eczema but failed to find evidence of a protective effect on eczema development at six to seven years of age [21].
Studies assessing the association between breastfeeding and food allergy have also had conflicting results. Some studies reported a reduced risk of food allergy development while others suggested a greater risk after breastfeeding [22-25].
Multiple studies have found associations between breastfeeding and lowered asthma prevalence in children; breastfeeding also appears to reduce the number of respiratory tract infections and risk of respiratory failure in infants [20,26-29]. However, these studies are all quite heterogeneous, with very different study designs and outcome definitions, making it difficult to draw unequivocal conclusions from them.
Breastfeeding is also associated with an increase in the size of the thymus, an essential organ for generation of T cell immunity and tolerance. Thymus size at four months of age in exclusively breast-fed infants was more than double the size in formula-fed infants, and this effect persisted at least until 10 months of age [30]. Breastfeeding between eight and 10 months also correlated with increased thymus size [31]. However, it is still unclear how this breastfeeding-related increase in thymus size occurs and how it affects immunity.
Another complication when investigating the effects of breastfeeding on allergy is that most current studies are observational, which means they can provide information about the association between the two factors but are unable to provide concrete evidence of any causal relationships. Randomized trials—where one group of infants would be randomly assigned to be breastfed while another group isn’t—would help establish causal relationships, but such studies would be unethical.
“It’s virtually impossible to randomize breastfeeding,” says Munblit. “You can’t just tell a mother, ‘I think you shouldn’t breastfeed,’” he says. The only randomized trial so far was conducted in Belarus, a country with very low breastfeeding rates, where mothers were randomized to a breastfeeding promotion group or continued standard practice [32]. The researchers found a reduced risk of early eczema with breastfeeding but no long-term protection against eczema, allergic rhinitis, and asthma at 6.5 years of age.
“One of the reasons behind all these conflicting results may be differences in methodology, because if you look the data is quite heterogeneous,” says Munblit. “There are really two very distinct types of studies: breastfeeding studies that assess breastfeeding association with regard to health outcomes, and other studies that assess human milk composition with regard to health outcomes,” he notes. “But there are no studies looking at both simultaneously,” says Munblit. “Also, for a long time there was a lot of heterogeneity in terms of breastfeeding definitions, and many people defined exclusive breastfeeding not as per the WHO definition,” he says. “Many systematic reviews and meta-analyses had to deal with many studies that were undertaken with very mixed definitions,” notes Munblit.
Human milk is also quite heterogeneous, which could explain differences between different studies [33]. “Current research lacks studies looking at breast milk composition as a whole,” says Munblit. “Those conflicting results that we see in the studies may be linked to breast milk composition, because composition varies from one woman to another, but it is not taken into account in large prospective breastfeeding studies.”
“What we need are really large sample size studies assessing multiple immunological factors, the microbiome, etc.,” says Munblit. “If we just look at the proteins in breast milk, there are more than 300, and in most of the studies only 10 or 15 are assessed, which means we are just assessing a very limited amount of immunological character,” he says. “So there’s a lot of work to be done.”
To account for the heterogeneity in human milk composition, future studies could attempt to characterize lactating women according to the constituents of their milk, forming so-called “lactotypes.” They could then examine whether different lactotypes are associated with specific immunological outcomes.
“What we hope to find are distinct lactotypes, maybe for women living in a particular geographic location, or maybe a particular lactotype, which is associated with the later development of a particular non-communicable disease,” says Munblit. “This is very preliminary, just a hypothesis, and something we would like to look at in the future,” he says.
Researchers are also increasingly beginning to consider the effects of food proteins, such as ovalbumin, in human milk, on allergies. “Maybe this is also a piece of the puzzle, because we know that food proteins are excreted into breast milk, and the degree of this excretion really varies from one mother to another,” says Munblit. “This is a really interesting topic, and we will most definitely see more data on the subject within the next year or two,” he suggests.
Researchers are interested in finding out whether interventions to modify human milk can influence allergy development in early infancy. Maternal lifestyle, including dietary habits and physical activity, can have a significant influence on the biologically active components of human milk [34-37]. Modifying one or more of these factors could potentially affect infant immunity. Probiotic administration, for example, may offer some protection against eczema [38]. But it’s still early days, and it’s unclear how well such interventions will work. “The basis of this research is quite controversial,” notes Munblit. “Some colleagues of mine believe that it is possible to modify breast milk composition, but others don’t believe that it would be possible to make this change.”
“Probiotics and prebiotics, fish oil, and fresh fish consumption are the interventions usually used for this purpose,” says Munblit. “Looking at some studies, fresh fish consumption is linked to changes in omega-3 and omega-6 fatty acid ratio in breast milk, and since it is assumed that polyunsaturated fatty acids are responsible in part for non-communicable disease risk reduction, including allergy, that brings some hope that we may influence breast milk composition by means of maternal diet changes,” he says. “We could then subsequently influence health outcomes, including allergic diseases.”
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