As discussed in the other blogpost CFTR gene cystic fibrosis (CF) is caused by a
defect in the CFTR gene. This gene is weakly expressed in the stomach, but more
strongly along the intestinal tract, the lungs and the pancreas.1 A
deficient CFTR function causes gastric acid in the intestine not to neutralize
properly. This results in a poor digestive function in the intestine.
Gastrointestinal tract manifestations in CF patients include meconium ileus
(MI), distal intestinal obstruction syndrome (DIOS), gastroesophageal reflux
disease (GER) and small bowel bacterial overgrowth.2.
 |
| Figure 1 O’Dwyer DN et al. The gut-lung axis.8 |
Research in gut-lung interaction in CF patients
As mentioned earlier, the gut microbiota are a more densely colonized surface of the human body than the lung microbiota. A study by Madan5 in children
with cystic fibrosis showed that there is constant cross-talk between the gut
and lung. This cross-talk between the gut and the lung is also known as the
gut-lung axis, which is defined as the immunological signalling that takes
place between the gastrointestinal tract and the respiratory tract and that is initiated
by changes in the microbial diversity. In the study, seven subjects with cystic
fibrosis were enrolled within a month of birth. The subjects were followed for
9 to 21 months, beginning at birth. Respiratory samples were taken using an
oropharyngeal swab and where then assessed using culture-independent evaluation
of respiratory microbes. Intestinal samples were taken using the stool of the
subjects. Overall, 59 samples were taken and analysed: 33 intestinal samples
and 26 respiratory samples. 16S rRNA gene pyrosequencing of the 59 samples was
then conducted. Madan3 found 8 genera for the intestinal and
respiratory microbiome samples. The most abundant species for the respiratory
samples were Streptococcus, Veillonella,
and Prevotella. For the intestine
this included Bacteroides,
Bifidobacterium and Veillonella. After
the samples were analysed for abundance, they were analysed for inter- and intra-individual
variation in the microbial composition and diversity in both samples. It
appeared that there was lower interindividual variation in the respiratory
tract than in the intestines. Madan3 also found some concordance
between the genera in both the gut and the respiratory tract when studying the
intraindividual variation and concluded from this that some bacteria were seen
in the gut prior to colonization of the respiratory tract. He also found that factors
such as diet have an impact on both the composition of the gut and lungs. Breast
milk seemed to have a greater impact on the microbiota in the respiratory tract
providing significant amount of Bifidobacterium
and Lactobacillus, while the
introduction of solid food, as expected, had a greater impact on the gut.
Study critics
As observed in the study by Madan, it is seen that patients with cystic fibrosis have both a dysbiotic airway and gut microbiota, which is usually the result of a loss in bacterial diversity due to the outgrowth of other pathogenic bacteria5. However, the outgrowth of a particular species in the polymicrobial community in the CF respiratory or intestinal tract is not necessarily sufficient in causing a disease. The pathogenic bacteria are able to live in a carrier state, without causing disease in the host7. Another discussion point of this study is the way samples were collected; the samples that are supposed to represent the respiratory tract microbiome were actually taken by an oropharyngeal swab. You may understand this swab matches the upper respiratory tract, but not the lower respiratory tract. As mentioned in another blogpost, these locations of the respiratory tract have different microbiota. Therefore, the question remains whether the results concluded from the study are correctly interpreted.
Study critics
As observed in the study by Madan, it is seen that patients with cystic fibrosis have both a dysbiotic airway and gut microbiota, which is usually the result of a loss in bacterial diversity due to the outgrowth of other pathogenic bacteria5. However, the outgrowth of a particular species in the polymicrobial community in the CF respiratory or intestinal tract is not necessarily sufficient in causing a disease. The pathogenic bacteria are able to live in a carrier state, without causing disease in the host7. Another discussion point of this study is the way samples were collected; the samples that are supposed to represent the respiratory tract microbiome were actually taken by an oropharyngeal swab. You may understand this swab matches the upper respiratory tract, but not the lower respiratory tract. As mentioned in another blogpost, these locations of the respiratory tract have different microbiota. Therefore, the question remains whether the results concluded from the study are correctly interpreted.
Future studies
In my opinion, it is important to do more research on the dysbiosis of the airway and gut microbiome in cystic fibrosis patients to fully understand the cause of recurrent infections in these patients and the correlation that the dysbiosis of the lung has to that of the gut. As seen in the study by Madan changes on the microbiome caused by nutrition could also be of importance for potential treatment of CF patients, without the use of antibiotics. This should, therefore, also be further investigated in future studies.
Written by Malak Al-Gawahiri
References:
1.
De Lisle RC, Borowitz D. The
Cystic Fibrosis Intestine. Cold Spring Harb Perspect Med. 2013 Sep; 3(9):
a009753. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753720/
. Last seen on Oct. 15th 2017.
2.
Sabharwal S. Gastrointestinal
Manifestations of Cystic Fibrosis. Gastroenterol Hepatol (N Y). 2016 Jan;
12(1): 43–47. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865785/
. Last seen on Oct. 15th 2017.
3.
Savage DC. Microbial ecology of
the gastrointestinal tract. Annu Rev Microbiol 1977;31:107–133. Available at: https://www.ncbi.nlm.nih.gov/pubmed/334036
. Last seen on Oct. 15th 2017.
4.
Sze MA et al. The lung tissue
microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med
2012;185:1073–1080. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22427533
. Last seen on Oct. 15th 2017.
5.
Madan JC, Koestler DC, Stanton
BA, Davidson L, Moulton LA, Housman ML, Moore JH, Guill MF, Morrison HG, Sogin
ML, et al. Serial analysis of the gut and respiratory microbiome in cystic
fibrosis in infancy: interaction between intestinal and respiratory tracts and
impact of nutritional exposures. MBio 2012;3:1–10. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428694/
. Last seen on Oct. 15th 2017.
6.
Marsland BJ et al. The Gut-Lung
Axis in Respiratory Disease. Ann Am Thorac Soc. 2015 Nov;12 Suppl 2:S150-6.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/26595731
. Last seen on Oct. 15th 2017.
7.
Rogers GB. Comparing the
microbiota of the cystic fibrosis lung and human gut. Gut Microbes. 2010
Mar-Apr; 1(2): 85–93. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023585/
. Last seen on Oct. 15th 2017.
8.
O’Dwyer DN et al. The Lung
Microbiome, Immunity and the Pathogenesis of Chronic Lung Disease. J Immunol.
2016 Jun 15; 196(12): 4839–4847. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894335/
. Last seen on Oct. 15th 2017.