Azithromycin may attenuate allergic airway inflammation associated with asthma via modulation of gut microbiota, according to findings from a mouse model published in the Journal of Allergy and Clinical Immunology.
Researchers from Korea compared cefixime vs azithromycin in ovalbumin-induced (OVA) mice with asthma during the OVA challenge period. This step was performed to induce changes in gut microbiota. Additionally, the microbiomes in bronchoalveolar lavage fluid (BALF) and feces were examined to characterize the mechanisms underlying the effect of gut microbiota on airway inflammation. A fecal microbiota transplantation (FMT) was also performed.
Mice treated with azithromycin had greater reductions in airway hyperresponsiveness as well as eosinophilia and interleukin (IL)-4/IL-5/L-13 in BALF compared with the cefixime-treated model and OVA-none group. According to the investigators, these findings suggest azithromycin therapy may function against airway hyperresponsiveness as well as airway inflammation in patients with allergic asthma.
Each group had significant alterations in gut microbial composition. In the fecal analysis, both azithromycin and cefixime were associated with reductions in the bacterial load but not in bacterial diversity. Azithromycin and cefixime almost eliminated Bacteroidaceae, the dominant gut microbiota in the control and OVA-none groups. Clostridiales, including Ruminococcaceae and Lachnospiraceae, were increased with azithromycin. There were no similar increases with cefixime.
Significant reductions were observed in airway hyperresponsiveness as well as eosinophil counts and Th2 cytokines in BALF following FMT. Post-FMT airway epithelium thickness and mucus production also decreased. The investigators suggested that this finding indicates the modulation effect of gut microbiota on airway inflammation during asthma exacerbations.
A potential limitation of this study was the inclusion of only mice, which restricts the generalizability of the findings across people with allergic asthma.
According to the researchers, these findings provide a preliminary glimpse into “the close interaction between airway inflammation and gut microbiota in allergic asthma controls.”
Park HK, Choi Y, Lee DH, et al. Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma [published online February 6, 2020]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2020.01.044