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We are thankful for the letter of Drs Dickson and Cox in response to our paper on the effect of the intestinal microbiota on host responses during pneumococcal pneumonia.1 We do agree that we cannot rule out that the antibiotics we used in our experiments could have influenced the microbiota in the airways and we do underwrite the importance of studying local host–microbe interactions within the respiratory tract during pneumonia. However, some points need to be addressed.
The relative importance of the microbiota of the lower airways, the area where alveolar macrophages reside, is a matter of debate. A study in humans showed that the microbiota that was sampled from the lower airways was mostly a reflection of contamination of the bronchoscope during passage through the upper airways.2 We think the articles cited by Dickson et al are of importance, but do not translate directly to our study. Segal et al showed that bacterial loads in bronchoalveolar lavage fluid are almost identical to those in sterile saline; this study therefore does not seem to be a very good one to support the idea that the lower airways harbour an important microbiota. Rogers et al investigated the microbiota present in the sputum, which is not necessarily representative of the microbiota in the lower airways. Slater et al investigated patients who have received azithromycin, which is an entirely different class of antibiotic. Finally, Gollwitzer et al studied neonatal mice, whose immune system is still developing and are therefore probably much more sensitive to these kinds of microbial disturbances. All of our experiments were conducted using mice between 10 and 12 weeks of age.
It should be emphasised that we used a cocktail of antibiotics (ampicillin, neomycin, vancomycin and metronidazole in drinking water of the mice) that mainly affect the gut microbiota. Neomycin and vancomycin are hardly absorbed by the gut. Penicillins such as ampicillin have recently been shown to have a relatively minor effect on the microbiota.3 ,4 Metronidazole mainly targets anaerobic bacteria, which are unlikely to be abundant in the lower airways. Faecal microbiota transplantation (FMT) was given by oral gavage: we administered the faecal substance into the stomach using a clean cannula. No bacteria other than Streptococcus pneumoniae were cultured from lung homogenates. FMT in gut microbiota-disrupted mice led to a normalisation of pulmonary bacterial counts, tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection, underscoring the effects of gut microbiota modulation on the host defence against pneumococcal pneumonia. We do acknowledge that we could only partially reverse the phenotype using FMT.
In summary, our study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. Changes in the lower respiratory tract microbiota are unlikely to be the main cause of the observed effect. Nonetheless, the potential role of the lung microbiota in the host defence against bacterial pneumonia will be a key topic for future research.
Contributors JML, TJS and WJW contributed equally to this letter.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
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