Asthma, Allergy, and the Microbiome

According to 2014 statistics from the Centers for Disease Control and Prevention (CDC), the prevalence of asthma is nearly 9% among individuals under 18 years of age. Asthma is a serious respiratory condition characterized by repeated episodes of wheezing, breathlessness, chest tightness, and nighttime or early morning coughing. A 2014 CDC report indicated healthcare costs associated with pediatric asthma were $272 million in 2010 among those enrolled in the Medicaid/Children’s Health Insurance Program (Pearson et al. 2014). Unfortunately, the causes of asthma and the “cure” for this complex malady remain uncertain.

There is interesting evidence that suggests the prevalence of asthma among children raised on dairy farms is lower than that observed among city dwellers (Wlasiuk and Vercelli 2012). The PASTURE study suggested prenatal exposure to the farming environment modulated inflammatory cytokines and thus may be protective against allergies and asthma among the offspring (Pfefferle et al. 2010). The earlier PARSIFAL (Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) study indicated maternal exposure to the microbial-rich farming environment may reduce atopic sensitization and increase expression of specific genes responsible for several receptors of the innate immune system (Ege et al. 2006).

The largest immune system in the human body in its spectrum of microbes is the gut (Takahashi and Kiyono 2014, Hooper et al. 2012). The full characterization of the microbiome remains to be determined, yet its impact on our immune system is dynamic, complex, and profound. Several recent publications advance the position that modulation of the microbiome may influence the risk of developing or may affect onset of asthma and allergy during early life (Azad et al. 2015, von Mutius 2016).

Studies with germ-free mice indicate allergen-induced responses were typically greater among these animals when compared with those colonized with microflora (Marsland and Salami 2015). What may be clinically significant is that the microflora among infants delivered by C-section differs from that of newborns presented vaginally (McCoy and Köller 2015). These two variables, plus environmental factors, influence the innate biodiversity during early life and therefore modulate immune regulation, such as immunoglobulin IgE, expression and secretion of inflammatory cytokines, and presentation of a potential imbalance of Th1 and Th2 helper cells (Cahenzli et al. 2013, Jakobsson et al. 2014). Remember, Th1 immunity cells, such as macrophages, function to eliminate intracellular bacteria following stimulation by several interleukins and related substances. On the other hand, Th2 immunity cells, which partner with B-cells, ward off extracellular pathogens and are modulated by other types of cytokines, including those that stimulate the production of IgE antibodies.

It is interesting to note that the placenta may present a unique microbiome (Aagaard et al. 2014). This report suggested the placental microbiome of nonpathogenic organisms presented and the taxonomic profile is similar to that of the human oral microbiome. Importantly, this microbiome may provide critical information to understanding preterm birth (Vinturache et al. 2016, Prince et al. 2016) and possibly in utero gut colonization (Collado et al. 2016). Some speculate perturbations of placental microbiome and gut microbiome may impact the development of immune function in the neonate and ultimately affect the advance of allergic disease (Lynch and Boushey 2016).

A landmark study of this hypothesis relative to asthma was initiated among more than 300 children who presented clinical wheezing at 12 months of age (Arrieta et al. 2015). The participants were a cohort from a larger longitudinal CHILD (Canadian Healthy Infant Longitudinal Development) study that focused on the gut microbiome and asthma. The Asthma Predictive Index, which is applicable to children between 2 and 3 years of age, demonstrated a 77% chance of active asthma among children at 3 years of age versus only a 3% risk of presenting asthma among control subjects. In addition, these findings were heightened among those children who also presented atopy. The authors concluded dysbiosis in early infancy, as supported by differences in fecal microbial profiles and urinary metabolites, may be considered asthma development risk factors.

The culmination of contemporary evidence suggests that placental microbiome, prenatal (maternal) exposures, and postnatal microbial environments during early life are significant variables that contribute to asthma development. The evidence also indicates that the diversity of microbial exposures account for variations in the human microbiota and its impact on allergies, asthma onset, and immune tolerance.

Roger Clemens, DrPH, CFS, Contributing Editor
Adjunct Professor, Univ. of Southern California School of Pharmacy, Los Angeles, Calif.
[email protected]