The oral microbiome may harbor harmful bacteria in CF patients

P. aureginosa (green line) is the most common cause of infection for CF patients older than 18 years old.

By Ninjatacoshell (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

Cystic fibrosis is a hereditary disease characterized by thick mucus secretions that obstruct the lungs and harbor harmful bacteria in a person’s airways. A common cause of death among CF patients is bacterial infection, usually by Pseudomonas aeruginosa, that subsequently leads to inflammation and respiratory failure. Scientists at the CF Reference Center in Roscoff, France were interested in a possible link between oral bacteria and lung bacteria of CF patients.  Specifically, they wondered if the mouth could harbor P. aeruginosa, which could then go on and inflame the lungs.  The results of their study were published in the Journal of Clinical Microbiology.

The researchers in France focused their study on detecting and measuring the genetic relatedness of P. aeruginosa in saliva and sputum (mucous) samples in 10 CF patients.  Of the 10 patients, 5 were chronically colonized (CC) by P. aeruginosa, with an average age of 23.8 years, and 5 were not colonized (NC), with an average age of 16.6 years. None of the patients had gingivitis or periodontitis.

No P. aeruginosa was detected in oral or sputum samples of NC patients, while 16 samples from the CC patients contained P. aeruginosa. Of the 16 sampled, six were salivary and ten were sputum. From these samples, the researchers discovered that the genetic make-up of the strain samples within each CC patient was more similar to other samples from the same patient than to those of other patients.

Overall, this study suggests that the oral cavity is a possible reservoir of P. aeruginosa and other bacteria that can infect the lungs. While this possibility is suggested by the discovery of similar P. aeruginosa strains in both saliva and sputum, it is not clear if the oral strains can actually descend and infect the lungs. As the article mentions, a longitudinal study that could follow the changes in bacterial colonization in CF patients would be beneficial. 

The lung microbiome changes during cystic fibrosis flare-ups

Cystic fibrosis is a genetically inherited disease characterized in part by thick mucus secretion that can obstruct the lungs and aid in the harboring of bacteria in airways. A leading cause of death within persons with cystic fibrosis (CF) is infection of the lungs and inflammation that leads to respiratory failure. In a study performed by members of the Department of Pediatrics and Communicable Diseases at the University of Michigan Medical School, and published by Microbiome, sputum (mucus) samples were taken from four CF patients over a period of a days leading up to pulmonary exacerbation, a period of worsening lung infection. The hope was to identify possible bacterial changes that lead to exacerbation.

 The samples collected from individuals with cystic fibrosis – referred to as subjects A, B, C, and D – were sequenced to identify bacterial and viral content during the period leading up to and including exacerbation. At baseline, the most abundant bacteria in subject A was Staphlyococcus, in subject C Streptococcus, and in subjects B and D Burkholeria. Subject A showed to most change in bacterial communities during the week prior to exacerbation symptoms, subject B showed bacterial community change just after onset of exacerbation, and subjects C and D remained relatively stable with the onset of exacerbation. After the changes that occurred in subject A’s bacterial community it never bounced back to its pre-exacerbation population, and stabilized to one with reduced Staphylococcus and increased Pseudomonas and Prevotella. Different from subject A, subject B’s bacterial community shifted one week after the onset of exacerbation from one dominated by Burkholderia  to Pseudomonas.

 While there were many differences among the four subjects sampled in the study, there was one similarity in that the dominant taxa of subjects A, B, and C all decreased in relative abundance around the period of exacerbation. The study’s findings also suggest that rather than changes in total bacterial density, it is more likely that shifts in relative abundance of a member of a bacterial community is associated with changes in CF symptoms. Additionally, none of the respiratory viruses tested for were found present during time of exacerbation, which was surprising to the researchers.

 The results of this study do not give us any solid rules for the characteristics of bacterial communities in the lungs during time of exacerbation in cystic fibrosis patients; however it is a step in the right direction toward identifying such characteristics. Perhaps with a larger sample size we can better understand the changes in community composition that lead to changes in CF symptoms.  

Microbiome link between cystic fibrosis and liver disease

Scientists have discovered a possible link between the microbiome and liver disease in individuals with cystic fibrosis.  Cystic fibrosis (CF) is a genetic disease that can be fatal and affects 30,000 people in the United States with another 1,000 diagnosed every year. While pulmonary disease is the most common cause of death in patients with CF, liver disease results in 2.5% of deaths and occurs in up to 72% of patients with the disease.  Approximately 5-7% of  these liver diseased CF patients have cirrhosis, a disease marked by the replacement of healthy liver tissue with scar tissue, preventing the liver from properly functioning.

A team of scientists from University of Colorado Medical Center recently published a study pertaining to CF patients with liver disease  in PLoS One. They studied 11 adolescents with CF and cirrhosis as well as 19 age-matched adolescents with CF without liver disease. They found that the two groups of patients had different gut microbiomes, leading the researchers to believe that there is communication between the gut bacteria and the liver, specifically in CF patients.

Patients with CF and cirrhosis had more severe lesions in their intestines than those without liver disease. Also, specific bacteria were less abundant in cirrhosis patients (e.g. Bacteroidetes) and others more abundant (e.g. Firmicutes) compared to CF patients without liver disease.    Similar ratios have been seen in other studies of liver disease and obesity.  However, we must remember that in complex diseases like CF, the microbiome is only one component of a very dynamic ailment, and at least one other disease study has measured the opposite Bacteroidetes/Firmicutes abundances.

Despite differences in previous studies and the lack of a mechanism relating the microbiome to cirrhosis, this identification of bacterial differences between CF patients with and without liver diseases is promising. The authors of the study point out that the sample size was small and this was only meant to be a pilot study but further longitudinal studies may now be warranted to investigate the development of cirrhosis in cystic fibrosis patients.