Lactoferrin (Lf) is a small molecule, as far as proteins go, with a bunch of glucose side chains, and is properly called a glycoprotein. Its structure is like a spring that coils onto itself which allows it to trap and hold minerals within its many folds. Lactoferrin is found abundantly in mothers’ milk, especially the first milk or colostrum that helps protect the newborn but is also present in other bodily fluids like tears, saliva, sweat, urine etc. signifying its importance as an important defence molecule. Lactoferrin plays an important role in a wide range of diseases which briefly can
The importance of the gut microbiome on multiple areas of our health is well-established. The gut microbiome, its diversity and the presence of specific species, has been linked to immune function (including inflammation), mental health, digestive health, nutrient status, and overall metabolic function. A mother’s gut microbiome plays a huge role during pregnancy as it greatly influences her baby’s immune system development and reactions. In doing so, it affects the incidence of atopic diseases in childhood such as asthma, eczema and allergies.1
Some of the earliest evidence of the link between bacteria exposure and the development of allergic diseases came from studying farming communities. Children who experienced early life exposure to farms, especially cattle, had a decreased risk of developing allergic reactions, including asthma and eczema, when compared to children living in suburban areas.1
Since then, research has been geared toward identifying the bacterial organisms and their mechanisms which modify immune responses and provide overall protection from atopic diseases. This helps establish therapies for pregnant mothers and their infants such as probiotics and non-digestible fibers that affect bacterial colonization.
Setting Up the Infant Immune System
An infant’s immune system is like a program that has to be written. It needs to learn the appropriate response to specific stimuli: which microbes are harmful and which are harmless or helpful. It also needs to allow the fetus to continue developing and growing without its immune system attacking the mother who provides nutrients, oxygen, hormones, signalling molecules and immune components through shared circulation.
There are several mechanisms in place to assist this: When maternal cells in the shared circulation reach the fetus’ lymph nodes they activate a specific type of white blood cell called regulatory T cells. It’s these specific T cells that protect the mother from immune attack.1
Immune components pass to the fetus as early as 13 weeks’ gestation, providing passive immunity for the fetus, but also to help the fetus develop its own immune system.1
After delivery, the newborn’s immune system is in a “TH2-dominant” state, where “TH” refers to helper T cells. This is important because the immune system has to start by learning not to fire inflammatory responses against harmless or even helpful bacteria. A TH2 state allows bacteria to colonize the infant’s gut. When this learning process is disrupted we see inflammation, tissue damage and improper immune system development.2
As the infant grows, the immune system will eventually shift to a TH1-dominant state so that as that child’s immune system can react appropriately with inflammation when it’s exposed to a pathogen.2
The mother can continue to provide compounds that affect the baby’s gut microbiome and immune system via breastmilk. In one study, breastfeeding was associated with higher amounts of Bifidobacteria in infant stool.3 This is likely due to the presence of prebiotics, called oligosaccharides, in human milk which help the gut microbiome to develop.3 These Bifidobacteria likely influence the activity of regulatory T cells and other components which affect immune reactions.3 Interestingly, infants with allergic diseases have significantly lower amounts of fecal Bifidobacteria.3
In addition to having fewer Bifidobacteria, children with allergic diseases also tend to have fewer Bacteroides and more Staphylococcus aureus and Clostridium difficile bacteria.2 This bacterial dysbiosis has been shown to increase the incidence of eczema at 18 months of age.2 Another study showed that having limited bacterial diversity and an abundance of Staphylococci bacteria at one month of age was associated with the development of hay fever by school age.2
Factors Affecting the Infant Gut Microbiome: Prebiotics and Dietary Fiber
As one of the factors that affects the gut microbiome, the maternal diet has been shown to influence allergy development later in childhood, as well as breastmilk composition.4 Some of the dietary components that have this effect include polyunsaturated fatty acids (such as Omega-3s), probiotics (either from fermented foods or from supplementation), and prebiotic fibres.4
Prebiotic fibres, often called “FOS” for fructooligosaccharides and “GOS” for galactooligosaccharides, can modify the gut microbiome. Specifically, these oligosaccharides are fermented by Lactobacilli, Bifidobacteria and other protective microbes and therefore increase the colonization and abundance of these bacteria.5
Put into clinical context, one study showed that supplementing formula-fed babies with a combination of FOS and GOS for the first 6 months of life led to lower rates of eczema compared to placebo.3 Another study found that the use of prebiotics reduced the incidence of atopic dermatitis by 44% at one year of age.3
In an animal study, when pregnant mothers were supplemented with prebiotics throughout their pregnancy it decreased the incidence and symptoms of dermatitis and allergic airway disease.1
A fibre-rich diet has a similar effect. When we consume dietary fiber, bacteria in the small intestine ferment these fibres which leads to the production of short-chain fatty acids (SCFAs). SCFAs influence the function of regulatory T cells and inflammation.1 When pregnant mice were fed a high-fibre diet, with resulting high SCFA levels, there was a corresponding increase in regulatory T cell levels compared to mice fed a fiber-free diet and those fed a control diet.1 Mice on the high fiber diet actually suppressed the ability for their offspring to develop allergic airway diseases.1
Effects of Early Antibiotic Exposure
A significant amount of development of the gut microbiome occurs in an infant’s first six months of life. This early process has long lasting effects on the immune system.
Antibiotic use is not uncommon in both pregnancy and early infancy. Their use is often assigned for urinary tract infections, respiratory infections, for the prevention of Group B streptococcus (GBS), and to prevent infections associated with birthing (such as during a caesarean section).2 In infants, antibiotics are most commonly used for acute ear infections, respiratory infections and fever.2
Although effective for killing or inactivating pathogenic bacteria, antibiotics can affect multiple bacterial species, including the beneficial and protective bacteria that reside in the gut. By reducing the bacterial diversity in the gut, it increases the susceptibility of pathogenic growth, changes in metabolism, and immune system impairment.2
In both cases, infant-use and maternal-use, antibiotic exposure can change the infant’s gut microbiome and the effect is greater with each course of treatment.2 For example, a systematic review found associations between prenatal antibiotic exposure and the incidence of childhood asthma of which ranged from 6%-14.8% with an increased risk for each additional course of antibiotics.2 A similar association was reported between early antibiotic exposure and childhood hay fever.2
Preventing Infant and Childhood Allergies
As the gut microbiome plays such an enormous role in immune development and allergic reactivity, substances which benefit the gut microbiome have been used to prevent atopic and allergic disease development. Many studies, including meta-analyses of clinical trials, have shown that supplementing with probiotics both during pregnancy and postpartum is effective for preventing food sensitivities and eczema, especially in infants who have a parent with an allergic disease.1
Not surprising, infants delivered by caesarean section may have a better response to supplementation with probiotics pre-and post-natal due to their reduced exposure to the mother’s flora during delivery.1
Probiotics are supplements taken with the goal of delivering specific bacterial species and strains to the gut to elicit a beneficial health response. It’s important to note that not all probiotics are equal, and that the specific strains used will ultimately change the overall outcome. When it comes to immune development and the incidence of allergic diseases, it’s crucial to use the correct strain(s).
Studies have showed that giving probiotics to mothers in the last weeks before birthing, and to the infant for the first few months, leads to reductions in eczema.3
In a double-blind randomized placebo-controlled trial, 188 mothers were given 100-million CFU of Lactobacillus reuteri ATCC55730 daily from week 36 of their pregnancy until delivery. Infants were then given the same probiotic supplement daily for the first year of life. Eight percent of the infants in the probiotic group had IgE-associated eczema from ages 12 to 24 months compared to 20% in the placebo group.6 Allergy skin prick test reactivity was also lower in the probiotic group compared to placebo (14% vs. 31%).6
Lactobacillus rhamnosus GG is another strain that has been studied in infant atopic diseases. In a double-blind, randomized placebo-controlled trial, mothers were given the L. rhamnosus probiotic at the end of pregnancy and to the infant for the first six months of life. The frequency of eczema in the probiotic group was 23% compared to 46% in the placebo group.7
However, one study actually showed a negative reaction to a probiotic: Researchers gave infants Lactobacillus acidophilus (LAVRI A1) daily for the first six months of life and found that it actually increased sensitization to food allergens, and notably to cow’s milk.8
A huge factor in the development of allergic diseases is the gut microbiome, including the diversity of species in the gut and the abundance of specific species. The foundation of this microbiome starts during gestation and is affected by the composition of the mother’s microbiome. Research has shown that prebiotics such as GOS, and certain species of probiotics, can modify and help colonize the gut with protective and helpful bacteria. Mothers, especially those with allergic diseases, may be able to use prebiotics and probiotics to help prevent their infants from developing improper immune reactions and atopic diseases in childhood.
- Vuillermin PJ, Macia L, Nanan R, et al. (2017). The maternal microbiome during pregnancy and allergic disease in the offspring. Semin Immunopathol. 39(6): 669-675
- Baron R, Taye M, Besseling-van der Vaart I, et al. (2020). The relationship of prenatal antibiotic exposure and infant antibiotic administration with childhood allergies: a systemic review. 20(1): 312
- Heine RG. (2018). Food allergy prevention and treatment by targeted nutrition. Ann Nutr Metab. 72 Suppl 3: 33-45
- van Neerven RJJ and Savelkoul H. (2017). Nutrition and allergic diseases. Nutrients. 9(7): 762
- Azcarate-Peril MA, Ritter AJ, Savaiano D, et al. (2017). Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals. PNAS. 114(3): E367-75
- Abrahamsson TR, Jakobsson T, Bottcher MF, et al. (2007). Probiotics in prevention of IgE associated eczema: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 119(5): 1174-80
- Kalliomaki M, Salminen S, Arvilommi H, et al. (2001). Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial. Lancet. 357(9262): 1076-9
- Taylor AL, Dunstan JA, Prescott SL. (2007). Probiotic supplementation for the first 6 months of life failed to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immune. 119(1): 184-91