154 Chapter 7 In summary, in this human proof-of-concept trial, we found no effect of short-term antibiotic-mediated gut microbiome modulation on lung inflammation of adults with allergic asthma. These findings argue against previous murine studies demonstrating a protective role of the gut microbiota in allergic asthma and contradict the hypothesis that broad-spectrum antibiotic-induced microbial disturbances induce pulmonary inflammation in patients with allergic asthma. This study underlines the importance of translating findings in animals to humans. Figure 1. A, Study design. 20 patients with asthma and house dust mite (HDM) allergy were challenged with installation of HDM plus lipopolysaccharide (LPS) by bronchoscopy. Prior to bronchoscopy, patients were randomized to receive either broad-spectrum antibiotics or no treatment. After a 36-hour wash-out period all patients were challenged through installation of HDM/LPS in one lung segment by bronchoscopy, after instillation of normal saline in a contralateral lung segment. Influx of eosinophils, neutrophils, and mediator release in the bronchoalveolar lavage fluid (BALF) were assessed seven hours later. B, Loss of Shannon diversity following antibiotic treatment. C, Relative proportion of sequence reads of the 15 most abundant families. Patients in the antibiotics group had a similar composition at baseline as patients from the control group. However, after antibiotic treatment their composition profoundly changed. D, Antibiotic-mediated gut microbiome modulation does not modify influx and composition of inflammatory cells after HDM/LPS challenge in patients with asthma and HDM allergy. In the boxplots, the rectangle spans the first quartile to the third quartile (interquartile range, IQR), the horizontal black line shows the median, and whiskers above and below the box. Data were analyzed using a Wilcoxon signed rank sum test. ***Denotes statistical significance with P<.001. ****Denotes statistical significance with P<.0001. n.s. denotes not significant.
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