How Microbes Took Your Breath Away: The Bacterial Roots of Asthma

New research in the journal Science Translational Medicine this past September raises concerns over the causes of childhood asthma.  Of the over 300-million people worldwide suffering from asthma, an immune-mediated inflammatory disease in the airways, a majority live in the developed world. This fact, along with other population-based studies, indicates that environment plays a vital role in asthma development, and our sterile first-world conditions may work against us.

It is believed in this case that environmental factors may alter human microbiota (the bacteria that live within us, specifically in our guts).  In their paper, “Early infancy microbial and metabolic alterations affect
risk of childhood asthma”, the research group proposes that altering microbiota in a critical window of human infancy compromises our natural protection and results in a lifelong immune reactivity.  An individual’s microbiome (the whole cast of bacteria living within us) is heavily influcenced by who we interact with, where we live, and the world immediately around us.

These bacteria don’t play a direct role in immune modulation; however, they produce a variety of metabolites during early life which are transported through the blood stream and facilitate many functions in growth and development.  For example acetate, a metabolite which has already been linked to the onset of asthma in animals, was found to vary in abundance depending on the composition of the gut microbiome.  Changes in bacterial metabolite production may also be linked to the incidence of allergies and other immune-linked disorders.

The Canada based research group assembled a cohort of 319 human subjects through the Canadian Healthy Infant Longitudinal Development (CHILD). Subjects were examined at one year of age, and their fecal microbiome was assessed. A large group experienced dysbiosis, or a dramatic change in microbiota composition, often due to antibiotic use. Subjects experiencing dysbiosis often exhibited symptoms such as atopy (being hyperallergic) or wheezing. Not only were the symptoms at one year predictive of the asthmatic state by age 3, but also they indicated the level of dysbiosis. Further, the group determined this response was time-sensitive – they defined a “critical window” being within the first 100 days of life, during which dysbiosis had a far stronger influence on development of asthma or allergies later in life.

The group went on to confirm that the dysbiosis in this critical window was responsible for the asthmatic symptoms.  They found four species of bacteria dubbed FLVR (Faecalibacterium, Lachnospira, Veillonella, and Rothia) were implicated in protection against developing immune-mediated conditions. In animal models the group demonstrated that removing and reintroducing FLVR could exacerbate and ameliorate asthma symptoms respectively.  Reintroducing FLVR also decreased the amount of responsive immune cells found in the lungs.

The model laid forth - gut microbiota produce metabolites, and these metabolites change in situations of early infant dysbiosis, which can lead to the development of asthma and other conditions. (Adapted from Thakur et al. J Pharmacol Clin Toxicol 2013.

The model laid forth – gut microbiota produce metabolites, and these metabolites change in situations of early infant dysbiosis, which can lead to the development of asthma and other conditions. (Adapted from Thakur et al. J Pharmacol Clin Toxicol 2013.

So the take-away message is that within the first 100 days of life children are most sensitive to disruptions in their microbiota, as certain bacteria like FLVR are required to produce the metabolites needed for healthy immune system formation.  This critical window is when the immune system is developing and the human body is trying to determine good from bad, and the metabolites produced in the gut play key roles in allowing your body to get it right.  Undergoing exposure to antibiotics and antibacterials, like many children in the Western world might, could induce dysbiosis, compromise their immune development, and predispose infants for diseases like asthma.

Clinically these findings inform doctors to be mindful of the importance of these first 100 days, and presents an opportunity for clinical and therapeutic intervention to maintain levels of FLVR and thus hopefully reduce the occurrence of asthma later in life.  Probiotic treatment of infants at this stage of development could drastically reduce the number children who contract asthma, making this finding potentially the biggest breakthrough in asthma research in years.


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