Treatment with the antibiotic vancomycin increases the severity of allergic asthma in young mice, researchers in Canada have revealed in a new study published in EMBO reports. The results are consistent with the "hygiene hypothesis" that links the loss of beneficial bacteria in the community of microorganisms in the gut, collectively known as the microbiota, to the onset of asthma.
Allergic asthma affects more than 100 million people worldwide and its prevalence is increasing, particularly among children in industrialized countries. Improved sanitation and widespread antibiotic use have been cited as possible reasons for the increase.
"We administered antibiotics to mice of different ages to determine if there was a link between the makeup of the microbial community in the gut and the extent of experimentally induced allergic asthma," said Dr. Brett Finlay, Professor at the Michael Smith Laboratories at the University of British Columbia, Canada. "Treatment of young mice with the antibiotic vancomycin reduced the diversity of microbes in the gut, significantly altered the composition of the bacterial population, and increased the susceptibility of young animals to experimentally induced asthma."
Many studies have suggested that the colonization of the gut early in life plays a substantial role in shaping the development of the immune system. More than 100 trillion bacteria, including more than 1000 bacterial species, colonize the human gut. If the balance of the microbial community in the gut is disrupted, the ability of the body to resist the onset of disease may be compromised.
Dr. Finlay remarked: "Although the precise link between the immune responses in the gut and lung remain unclear, we think that vancomycin selects for a community of microbes in the gut that somehow disrupts the inflammatory and regulatory immune responses at the two different sites. In mice, the restructuring of the intestinal microbial population during infancy after antibiotic treatment is enough to lead to exacerbated asthma."
The scientists used genome sequencing of the microbial population to reveal the diversity of the microbial community. The severity of asthma was assessed by different molecular assays and direct examination of lung tissue.
Said Finlay: "Our results confirm that the early months of life are a crucial time in which the gut microbial community may influence key immunological events that alter the sensitivity of the body's immune system to the response to allergens."
The work is part of the CIHR Canadian Microbiome Initiative, which was created to provide an opportunity for Canadian researchers to contribute to international efforts to understand the role of the human microbiome in health and disease.
- Shannon L Russell, Matthew J Gold, Martin Hartmann, Benjamin P Willing, Lisa Thorson, Marta Wlodarska, Navkiran Gill, Marie-Renιe Blanchet, William W Mohn, Kelly M McNagny, Brett B Finlay. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO reports, 2012; DOI: 10.1038/embor.2012.32
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