Which Factors Influence Atopic March?

In recent years, several factors have been identified to either contribute to or prevent atopic march. Do you know what they are?

Atopic march (in French)is defined as the progression of an atopic disorder into an allergic disease, such as allergic rhinitis, asthma, or food allergy. Here is a list of factors thought to influence this progression.

Eczema: a risk factor

Eczema, also known as atopic dermatitis, is the first stage of atopic march leading to the development of allergic diseases. It, therefore, constitutes a risk factor.

But why?

Inflammation caused by eczema creates defects in the skin barrier, which facilitates the passage of allergens and therefore favors sensitization to those allergens [1]. This is referred to as epicutaneous exposure (in French).

The earlier eczema appears (ex: within the first few months of a child’s life), the higher the risk of developing an allergic disease [2].

Air pollution: a risk factor

Living in a large city and being exposed to air pollution on a daily basis is believed to promote the development of atopy in young children, according to a 2015 Canadian study.

These Canadian researchers examined the association between the airborne concentration of NO2, an air pollutant, and the presence of atopy in nearly 2,500 one-year-olds living in the cities of Toronto, Vancouver, Edmonton, and Winnipeg. Their findings: exposure to NO2 during the first year of life was associated with a higher rate of atopy when the child reached one year of age.

Antacid intake during pregnancy: a risk factor

It appears that maternal antacid intake during pregnancy increases the risk of the unborn child developing asthma [3]. The hypothesis is that by neutralizing gastric acid, antacids prevent proper digestion of allergenic proteins in the mother’s stomach. In doing so, the allergens could cross the placenta and cause fetal sensitization, thereby increasing the risk of atopy and the development of allergic diseases. Further research is needed to confirm these findings.

Composition of the intestinal flora: risk and preventive factors

The intestinal flora develops during the first few months of an individual’s life. This is when the intestine is colonized by different types of bacteria, good or bad. Therefore, the risk of allergen sensitization varies, depending on the types and diversity of bacteria that take up residence in a child’s intestine.

There is still a lot of research to be done on the intestinal flora in order to identify the bacterial species that influence atopic march. A few studies have already provided us with some possible explanations:

• In 2012, researchers observed low microbial diversity in the intestinal flora of one-month-old children who were later diagnosed with atopic dermatitis [4].
• Three years later, Canadian researchers observed that low microbial diversity in the intestinal flora of young children, combined with a high ratio of bacteria from the Enterobacteriaceae / Bacteroides families, is associated with a higher prevalence of food allergen sensitization [5].
• Some bacterial species may influence the risk of developing eczema. For example, in 18-month-old children with atopic dermatitis, researchers have observed a low diversity of bacteria from the Bacteroides family, but an abundance of other species, including the Clostridium family [6].  It’s important to point out that several factors seem to influence the composition of the intestinal flora during the first months of a child’s life. Here are a few:
• The birth method. A natural birth (i.e. a vaginal birth) is believed to allow the newborn to be colonized by the bacteria naturally present in the mother’s intestinal and vaginal flora. Its intestinal flora would therefore be more diversified than that of a baby born by caesarean section in a sterile environment [7].
• Infant diet. In all likelihood, breastfed babies would have a less diversified bacterial flora than babies fed with a commercial formula [8]. However, the presence of various metabolic substrates in breast milk would allow the “good” bacteria to proliferate, which would have a preventive effect on atopic march in breastfed children.

Click  for more information on intestinal flora (in French).

Needless to say there are several more factors that influence the atopic march, such as genetics, having several siblings and living on a farm or with pets, to name a few. The complexities related to allergic conditions pose many questions that science continues to answer bit by bit over time. One can hope that the answers to come will identify factors over which we have control.

[1] Heratizadeh, A., Wichmann, K., Werfel, T. (2011). Food allergy and atopic dermatitis: How are they connected? Current Allergy and Asthma Reports, 11(4):284-291.
[2] Reynolds, L. A. et Finlay, B. B. (2017). Early life factor that affect allergy development. Nature, 17:518-528
[3] Hak, E. et coll. (2013). Use of acid-suppressive drugs in pregnancy and the risk of childhood asthma: Bidirectional cross-over study using the general practice research database. Drug Safety, 36(11):1097-1104.
[4] Abrahamsson, T. R. et coll. (2012). Low diversity of the gut microbiota in infants with atopic eczema. Journal of Allergy and Clinical Immunology, 129(2): 434-440.
[5] Azad, M. B. et coll. (2015). Infant gut microbiota and food sensitization: associations in the first year of life. Clinical & Experimental Allergy, 45:632-643.
[6] Nylund, L. et coll. (2013). Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiology, 13:12
[7] Jakobsson HE et coll. (2014). Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut, 63(4):559-66.
[8] Azad, M. B. et coll. (2013). Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. Canadian Medical Association Journal, 185(5):385-394.