lung microbiome

so, here's another microbiome article -- as mentioned in previous blogs, i do find this microbiome stuff fascinating and have sent out articles on gut and lung microbiomes in the past, in part because it gives us a mechanistic window into the rather profound relationship between the environment and disease (eg, the TMAO study showing that for red meat eaters, as opposed to vegan eaters, there is a change in the gut microbiota so that if given a red meat meal, more cardiotoxic TMAO is generated --see cad red meat TMAO nature medicine 2013 in dropbox, or doi:10.1038/nm.3145), and i think this microbiome focus provides even greater imperative to avoid overuse of antibiotics (which profoundly change the microbiota) and possibly increase use of probiotics. recent review article in Lancet has current insights into lung microbiome and disease (see lung microbiome and disease lancet 2014 in dropbox, or Lancet 2014; 384: 691–702​). brief summary of key points:

--microbes normally enter the lungs continuously through inhalation of air with 10⁴-10⁶ bacterial cells per m³, and microaspiration of microbe-dense upper airway (which happens all the time even in healthy people)

--microbes are removed regularly by mucociliary clearance, cough and local immunity (innate and adaptive)

--the above changes dramatically in disease (eg, impaired mucociliary clearance, increased aspiration, increased mucous which provides nutrient-rich bacterial growth medium, impaired local immunity, and the effects of antibiotics given)

--COPD: exacerbations clearly related to virus (eg inoculation with rhinovirus causes exacerbation), but also exacerbations sometimes assoc with new strains of bacteria introduced into respiratory tree, and overall studies have found that exacerbations overall are associated with selective increase in specific bacteria (hemophilus, pseudomonas, moraxella), and that even after viral exposure, there is a shift of bacterial species (towards the Proteobacteria phylum, which includes hemophilus, pseudomonas, klebsiella), and this microbiota change can persist for at least 6 weeks after a viral infection. though important to remember that the role of antibiotics in COPD treatment is controversial.

--asthma: even more than in COPD, associated with viruses and not bacterial infection.some data of increased prevalence of chlamydia and mycoplasma with exacerbations. respiratory microbiome is different in asthmatic vs nonasthmatic patients, even in asymptomatic asthmatic patients, with abundance of Proteobacteria. some data that airway hyperresponsiveness tracks with bacterial diversity and composition (esp increase in Proteobacteria)

--cystic fibrosis: more diversity in microbiota than previously suspected. exacerbations not associated with increased bacterial density or decreased microbiome diversity (as happens in pneumonia). microbiota changes between baseline and exacerbation, esp in pseudomonas

--bronchiectasis: some data that microbiota dominated by Proteobacteria. similar to cystic fibrosis

--idiopathic pulm fibrosis: some recent studies have found potential role of bacterial lung microbiome in progression and exacerbations of IPF

--so, their conclusion: the issue is not presence of bacteria in above clinical conditions, but "dysbiosis" -- changes in the microbiota/ dysregulation of immune response, which can be from a viral or allergic trigger, and perhaps the effects of the inflammatory response.

--2 RCTs have shown benefit from enteric probiotics in decreasing frequency of cystic fibrosis exacerbations

i did send out an interesting article on increasing dietary fiber in mice leading to changes in the microbiome in both the gut and lung, and decrease in allergic inflammation and improved lung function (see asthma microbiome nature medicine 2014 in the dropbox, or doi:10.1038/nm.3444),