How To Avoid The Atopic March

Summary

  • The atopic march begins early in life with eczema. It then continues through childhood and into adulthood. The conditions that we see in the atopic march include eczema, food allergies, and asthma and/or allergic rhinitis.
  • Your baby relies on "old friends," or lost beneficial bacteria, to help train their immune system.
  • Beneficial bacteria protect against the atopic march.
  • To make sure your baby has beneficial bacteria, be sure to support microbiome seeding with a vaginal birth and breastfeeding. You may also want to periodically test your baby’s gut to check for butyrate-producers.

The atopic march refers to eczema, food allergies, and asthma. This cluster of chronic conditions has everything to do with your baby’s immune system and its development. Typically, one problem - starting with atopic eczema - tends to follow another.

What is the atopic march?

The atopic march describes the flow from one allergic disease to another.

Often, the atopic march begins early in life with eczema. It then continues through childhood and into adulthood. The cluster of conditions that we see in the atopic march includes:

  • Atopic eczema
  • IgE-mediated food allergies
  • Asthma and/or allergic rhinitis [1], [2]

IgE-mediated allergies are often called “atopy.” Atopy refers to how the immune system might react to an allergen, evoking a strong response. This then leads to the overproduction of an antibody known as IgE (immunoglobulin E) [1].

IgE antibodies travel to cells that release chemicals, causing signs of an allergic reaction.

An IgE response occurs within 5 - 30 minutes and usually shows up in the nose, lungs, and throat, or on the skin. During an IgE response, you may see:

  • Sneezing
  • Coughing
  • Rashes
  • Wheezing and asthma attacks

An IgE-mediated allergy includes eczema, IgE-mediated food allergies, asthma, and allergic rhinitis.

The first step of the atopic march

Broadly speaking, IgE-mediated allergies can often be traced back to eczema early in life.

Eczema is tough to treat. When it goes unresolved, the immune system remains in an alert state. This is the first step of the atopic march. Then, other forms of allergic conditions tend to follow.

And indeed, researchers have reported that babies with eczema within the first year of life are 11x more likely to develop peanut allergy at 12 months old [3]. This means that 1 in 5 babies with eczema will develop peanut allergy in comparison to the 1 in 25 healthy babies who have never had eczema.

Children with eczema are also 6x more likely to develop egg allergy [3]. What’s more, studies show that 50% of children with food allergies during their first 4 years are more likely to develop respiratory allergies at 4 years old [4].

Your baby’s immune system relies on “old friends”

Your baby’s first 1,000 days includes nine months of pregnancy and the first two years. During this time, researchers have noted that exposure to allergens matters. This is also when your baby’s microbiome goes through a unique period of development and maturation.

The old-friend hypothesis, introduced in 2003, tells us that humans have lost beneficial bacteria over the past century. These “old friends” are an intrinsic part of our microbiome and help to train the immune system from the moment we are born [5].

This loss comes on the heels of better hygiene and very clean environments.

While we want to control the growth of unfriendly bacteria and avoid infection, it’s also thought that these missing microbes help the immune system to discern between harmless and harmful substances. This is known as the hygiene hypothesis [6], [7].

For example, it’s been found that children of full-time and part-time farmers have a lower risk for pollen allergies and atopic sensitization [8]. Because farmers are in regular contact with soil and diverse bacterial communities, this may help to protect against allergies, including asthma [9], [10].

Beneficial bacteria protect against the atopic march

Whether we’re missing our “old friends” or modern living in urban spaces has taken a toll on our microbes, research suggests that the atopic march of eczema, allergies, and asthma may be linked to a baby’s gut microbiome.

When we look a little closer at patterns of colonization in babies, we see that the presence or absence of certain bacteria may influence the trajectory of a baby’s immune development.

For example, missing beneficial bacteria have been linked to the development of eczema [11]-[18]. This includes bacteria that make a short-chain fatty acid called butyrate. Butyrate has anti-inflammatory effects. It can also help to promote immune tolerance and protect against allergies.

In 2019, researchers from the University of Chicago, Argonne National Laboratory and the University of Naples Federico II in Italy found a cause-and-effect relationship between the early microbiome and food allergies [19].

For this study, scientists transplanted bacteria from eight babies into germ-free (or sterile) mice. Four babies were healthy and the other four had been diagnosed with cow’s milk allergy. Mice that received bacteria from babies with cow’s milk allergy later had a severe allergic response when exposed to cow’s milk. However, mice that received bacteria healthy babies showed no signs of an allergic response when exposed to cow’s milk.

This study helps to show how a baby’s microbiome early in life can help to protect against the development of food allergies. Once again, a key player is the short-chain fatty acid, butyrate - along with the bacteria that make it.

How to avoid atopic eczema, allergies, and asthma

With allergies on the rise worldwide, there’s a strong interest in seeing the risk of allergies and atopic conditions drop [20]. But we’re not there yet.

So far, science points to the early microbiome and immune development. The trouble is that many lifestyle factors get in the way of establishing a healthy microbiome. Like over-sanitization and distance from “old friends” that help to tone a baby's immune response. Or a lack of social structures that support breastfeeding parents. Even factors like hospital care or how we do C-section birth could use some updates.

While we piece together how to encourage healthy immune development, here’s what you can do to protect your baby’s beneficial bacteria:

References

[1] Hill, D. A. & Spergel, J. M. The Atopic March: Critical Evidence and Clinical Relevance. Ann Allergy Asthma Immunol 120, 131–137 (2018).

[2] Justiz Vaillant, A. A., Modi, P. & Jan, A. Atopy. in StatPearls (StatPearls Publishing, 2020).

[3] Martin, P. E. et al. Which infants with eczema are at risk of food allergy? Results from a population-based cohort. Clin Exp Allergy 45, 255–264 (2015).

[4] Chiu, C.-Y. et al. Sensitization to Food and Inhalant Allergens in Relation to Atopic Diseases in Early Childhood: A Birth Cohort Study. PLOS ONE 9, e102809 (2014).

[5] Rook, G. A. W., Martinelli, R. & Brunet, L. R. Innate immune responses to mycobacteria and the down-regulation of atopic responses. Current Opinion in Allergy and Clinical Immunology 3, 337–342 (2003).

[6] Strachan, D. P. Hay fever, hygiene, and household size. BMJ 299, 1259–1260 (1989).

[7] Scudellari, M. News Feature: Cleaning up the hygiene hypothesis. Proc Natl Acad Sci U S A 114, 1433–1436 (2017).

[8] Riedler, J., Eder, W., Oberfeld, G. & Schreuer, M. Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin Exp Allergy 30, 194–200 (2000).

[9] Depner, M. et al. Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma. Nature Medicine 26, 1766–1775 (2020).

[10] Riedler, J. et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358, 1129–1133 (2001).

[11] Galazzo, G. et al. Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood. Gastroenterology 158, 1584–1596 (2020).

[12] Fujimura, K. E. et al. Neonatal gut microbiota associates with childhood multi–sensitized atopy and T–cell differentiation. Nat Med 22, 1187–1191 (2016).

[13] Cait, A. et al. Reduced genetic potential for butyrate fermentation in the gut microbiome of infants who develop allergic sensitization. J Allergy Clin Immunol 144, 1638-1647.e3 (2019).

[14] Park, Y. M. et al. Imbalance of Gut Streptococcus, Clostridium, and Akkermansia Determines the Natural Course of Atopic Dermatitis in Infant. Allergy Asthma Immunol Res 12, 322–337 (2020).

[15] Wang, H. et al. Dysfunctional gut microbiota and relative co-abundance network in infantile eczema. Gut Pathog 8, 36 (2016).

[16] Wopereis, H. et al. Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development. J Allergy Clin Immunol 141, 1334-1342.e5 (2018).

[17] West, C. E. et al. Gut microbiome and innate immune response patterns in IgE-associated eczema. Clin Exp Allergy 45, 1419–1429 (2015).

[18] Zhang, Y. et al. Variations in early gut microbiome are associated with childhood eczema. FEMS Microbiol Lett 366, (2019).

[19] Feehley, T. et al. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat Med 25, 448–453 (2019).

[20] Platts-Mills, T. A. E. The allergy epidemics: 1870-2010. Journal of Allergy and Clinical Immunology 136, 3–13 (2015).