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Thursday, January 8, 2015

The Microbiome in Asthma

Newly developed culture-independent methods for microbial detection are deepening the understanding of their role in lung disease. A persuasive body of evidence suggests that the microbiome of the lower airways differs distinctly in the obstructive lung disease, including asthma. Huang and Boushey provide their perspective on the findings of studies of differences in the airway microbiome in patients with asthma vs. healthy subjects, and of studies of relationships between environmental microbiota, gut microbiota, immune function, and the development of asthma (J Allergy Clin Immunol 2015; 135: 25-30). Additionally, they provide a rationale for approaches involving directed manipulation of the gut and airway microbiome for treatment and prevention of allergic asthma.

Alterations in respiratory tract immune function are at least theoretically linked to the immunomodulatory activity of gut microbiota through the concept of a “common mucosal response”. This proposes that antigen presentation at one mucosal site stimulates migration of lymphoid cells to other mucosal sites, shaping immune responsiveness at those sites as well. Studies in mice provide strong support for the concept that bacterial community composition of the gut can shape developing immune function to foster or protect against allergic sensitization.   Similarly, studies focused exclusively on lung microbiota suggest that establishment of a lung microbiome occurs and is a dynamic process after birth. The authors discuss relationships of gut microbiota in response to viral respiratory infection, and provide findings that bacteria regulate immune defense against viral infections in mouse models. For example, interaction between exposure to allergens and microbial exposure has been seen in inner city children. Surprisingly, children with the highest rates of atopic sensitization and recurrent, presumably virus induced wheeze were found in children exposed to the lowest levels of cockroach, mouse and cat allergen and the lowest levels of bacterial diversity in their first year of life. On the contrary, the lowest rates of atopy and wheezing were found in those who had been exposed to the highest levels of these allergens and bacterial diversity. These results suggest that the bacteria served as a tolerance-inducing adjuvant for allergens.

The authors emphasize that dissecting the role of the microbiome in asthma is challenged by the heterogeneity of the disease at multiple levels. These levels include asthma’s clinical and inflammatory heterogeneity, genetic factors that contribute to asthma risk, and the multiplicity of immune pathways involved in asthma. To progress to clinical studies of oral or aerosol administration of microbiota for treatment and especially for prevention of asthma which will necessarily involve enrollment of pregnant women or of newborn infants will likely require overcoming ethical, legal, and cultural hurdles as high as the scientific ones we currently face.

Question for the authors:
The studies described in your review focus on the early development of the mucosal microbiota. Is there evidence that manipulating the microbiota in adults with allergic asthma may be a potential therapeutic?

We are a long way from human studies of the effects on allergic or asthmatic symptoms of manipulating the microbiota in adults with the condition. So the evidence available is largely from studies of mice, like Karimi et al’s study showing that dietary supplementation with L. reuteri increased Treg cell number and activity and reduced the allergic inflammation induced by allergen challenge in previously sensitized and challenged BALB/c mice (Am J Respir Crit Care Med Vol 179. pp 186–193, 2009).  Nothing comparable has been done in humans with established allergic asthma.

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