Published Online: August 18, 2014
The incidence of lung inflammatory disease is increasing at an alarming rate, yet what makes some individuals susceptible and others resistant is largely unknown. In a new team study published in The Journal of Allergy and Clinical Immunology, S. Russell, M Gold and colleagues show that antibiotic driven alterations of the neonatal gut microbiome / bacteria can have remarkably selective effects on future susceptibility to subtypes of lung inflammatory disease.
Previously, the authors of this study showed that mice treated early in life with low doses of the antibiotic, vancomycin (but not streptomycin), developed an increased susceptibility to an allergic asthma-like disease as adults. This enhanced susceptibility was the result of a broad shift in the type of bacteria that normally colonize the intestines of mice shortly after birth. Shifting neonatal bacteria, in turn, resulted in long lasting alterations in development of the immune system and ultimately a greater susceptibility to allergic asthma in adults. In the new study, the authors extend these results to show that a different antibiotic, streptomycin (but not vancomycin), increases susceptibility to a very different type of lung inflammatory disease, hypersensitivity pneumonitis. Strikingly, the authors found a direct correlation between the frequency of certain subsets of bacteria in these mice and the severity of their disease response. As lung diseases go, allergic asthma and hypersensitivity pneumonitis couldn’t be more different: allergic asthma is a very common disease of the airways and is driven by Th2 cells, mast cells, eosinophils and IgE antibodies, while hypersensitivity pneumonitis is a more rare disease of the alveoli, driven by neutrophils and Th17 cells. Thus, these studies suggest that the bacteria that colonize the newborn intestine can have a very nuanced effect on future susceptibility to specific disease.
In aggregate, these studies provide further evidence that bacterial colonization of the intestine shortly after birth plays an extremely important role in shaping the development of the immune system. They also show that antibiotic-driven shifts in resident flora during this period can have remarkably selective effects on future susceptibility to distinct types of lung inflammation. Finally, they hint that it may be possible to facilitate colonization of the neonatal gut with beneficial bacteria as a prophylactic.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.