Finlay Asthma 001
Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma
Allergic asthma rates have been steadily rising in developed countries over the last several decades, arguing for an environmental etiology. Since the hygiene hypothesis was initially proposed, epidemiological studies have pointed to a role for the infant gut microbiota in immune system development that could alter allergic disease susceptibility. To assess the influence of gut microbiota on asthma, we treated neonatal mice with clinical doses of two widely used antibiotics (streptomycin and vancomycin) and evaluated resulting shifts in resident flora and subsequent susceptibility to experimental allergic asthma. Streptomycin treatment had little effect, whereas vancomycin enhanced disease severity, demonstrated by increases in airway inflammation, antigen-specific IgE, lung pathology, and airway hyperresponsiveness. Neither antibiotic had a significant effect when administered to adult mice. Analysis of the intestinal microbial communities from untreated and antibiotic-treated mice revealed that streptomycin-treated microbiota was much more similar to untreated than vancomycin-treated. Community membership in the microbiota of vancomycin-treated animals was drastically altered compared to the untreated controls, which coincided with a significant decrease in overall diversity. Interestingly, reduced colonic regulatory T cells were also observed in the vancomycin-treated animals. Consistent with the “hygiene hypothesis” our data argue for a neonatal, specific microbiota-driven increase in susceptibility to asthma.
Allergic asthma rates have increased steadily in developed countries arguing for an environmental etiology. To assess the influence of gut microbiota on experimental murine allergic asthma, we treated neonatal mice with clinical doses of two widely used antibiotics (streptomycin and vancomycin) and evaluated resulting shifts in resident flora and subsequent susceptibility to allergic asthma. Streptomycin treatment had little effect, whereas vancomycin enhanced disease severity. Neither antibiotic had a significant effect when administered to adult mice. Consistent with the “hygiene hypothesis” our data argue for a neonatal, specific microbiota-driven increase in susceptibility to experimental murine allergic asthma.