David Dorward; Ph.D.; National Institute of Allergy and Infectious Diseases (NIAID)
Pneumonia, a bacterial infection of the lungs, is a prominent health threat worldwide. True to its name, the bacterium Klebsiella pneumoniae is a key cause of pneumonia, particularly in healthcare settings. Unfortunately, a number of K. pneumoniae strains are multi-drug resistant, which limits the repertoire of antibiotics capable of treating infection. Discovering therapeutics to combat these feisty microbes is a pressing need.
Where should we look for such therapies? A recent study suggests the gut microbiota might be a good place to start.
Scientists found that mice whose gut microbiota were depleted by antibiotics developed more severe K. pneumoniae infection compared to mice with an intact microbial community. Interestingly, alveolar macrophages (a type of immune cell that resides in the lung and “eats” microbial invaders) isolated from antibiotic-treated mice were less able to engulf and eliminate K. pneumoniae cells. These results suggest the gut microbiota play a role in K. pneumoniae lung clearance. The question is, how?
As gut bacteria go about the business of living, they release small molecules, called metabolites, that circulate throughout the body and interact with our cells to keep us healthy. The scientists observed decreases in several microbiota-derived metabolites in the guts of antibiotic-treated mice.
Interestingly, if mice were fed these metabolites prior to K. pneumoniae infection, they developed fewer bacteria in their lungs and less severe disease. Furthermore, the metabolites increased the ability of alveolar macrophages to consume K. pneumoniae and increased cell activity involved in bacterial clearance, thus supporting the idea that these compounds help macrophages fight K. pneumoniae infection.
These exciting observations provide a basis for developing gut microbiota-associated therapies to prevent or treat pneumonia. More broadly, they add to the mounting body of evidence that gut microbes do important work both inside and outside their intestinal home.