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. Author manuscript; available in PMC: 2017 Aug 1.
Published in final edited form as: Gut. 2016 Apr 1;66(2):384. doi: 10.1136/gutjnl-2016-311823

Letter to the editor of Gut

Robert P Dickson 1, Michael J Cox 2
PMCID: PMC5083249  NIHMSID: NIHMS824096  PMID: 27037327

Dear Editor

We read with interest the work by Schuijt et al[1] reporting that sustained treatment with broad- spectrum antibiotics increases the susceptibility of mice to pneumococcal pneumonia, an effect that is reversed via faecal microbiota transplantation (FMT). Yet we question the authors’ confidence that this effect is entirely attributable to alterations in gut microbiota.

Antibiotic therapy, as used by the authors, alters the microbiota of the upper and lower respiratory tract[2, 3]. The authors used FMT to determine that the protective effect was due to gut microbiota, yet their protocol for FMT - oral gavage with faecal material – is also a direct manipulation of the microbiota of the upper respiratory tract. Differences in respiratory microbiota correlate strongly with alterations in the abundance and behavior of alveolar inflammatory cells[4, 5].

We thus wonder why the authors conclude that the effects of antibiotics and FMT on pneumonia susceptibility were attributable specifically to alterations of lower gastrointestinal tract microbiota. The authors’ interventions surely changed the respiratory microbiota of their mice, suggesting a more direct mechanistic explanation. To provide a specific example: the differences reported in the behavior of lung-resident macrophages are plausibly explained by differences in local microbial exposure. Why, then, do the authors conclude uncategorically that “the gut microbiota enhances primary alveolar macrophage function”?

The authors’ invocation of a “gut-lung axis” may obscure the importance of local host-microbe interactions within the respiratory tract, which require fewer mechanistic assumptions and are of immediate relevance to our understanding of the pathogenesis of pneumonia.

References

  • 1.Schuijt TJ, Lankelma JM, Scicluna BP, de Sousa e Melo F, Roelofs JJTH, de Boer JD, et al. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut. 2016;65:575–83. doi: 10.1136/gutjnl-2015-309728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Slater M, Rivett DW, Williams L, Martin M, Harrison T, Sayers I, et al. The impact of azithromycin therapy on the airway microbiota in asthma. Thorax. 2014;69:673–4. doi: 10.1136/thoraxjnl-2013-204517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Rogers GB, Bruce KD, Martin ML, Burr LD, Serisier DJ. The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial. Lancet Respir Med. 2014;2:988–96. doi: 10.1016/S2213-2600(14)70213-9. [DOI] [PubMed] [Google Scholar]
  • 4.Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B, Gao Z, et al. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome. 2013;1:19. doi: 10.1186/2049-2618-1-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Gollwitzer ES, Saglani S, Trompette A, Yadava K, Sherburn R, McCoy KD, et al. Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Nat Med. 2014;20:642–7. doi: 10.1038/nm.3568. [DOI] [PubMed] [Google Scholar]

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