Streptomycin Seen to Ease Airway Hyper-Responsiveness in CF Mouse Model

A study reported that treating a mouse model of cystic fibrosis (CF) with the antibiotic streptomycin eased the animals’ airway hyper-responsiveness. The improvement in airway function was accompanied by an altered immune profile and changes in a certain bacteria in the gut.

The study, titled “Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model,“ by Mark Bazett and colleagues from McGill University, Canada, was published in the journal Scientific Reports on Jan. 12, 2016.

In addition to the lung disease, CF patients often have symptoms involving the gut and the bones. The intestinal disease is characterized by bacterial overgrowth in the small intestine and a bacterial imbalance observed in the feces.

Mice lacking the CFTR gene (which is linked to CF) showed all the pathological changes characterizing CF, including airway hyper-responsiveness, and bone and intestinal complications.

Previous studies have shown that the gut microbiome can also influence lung and bone disease in mouse models. Researchers believe that changes in the gut microbiome could result in an altered immune activation, which potentially affects disease in other organs.

The research team treated both normal mice and mice lacking CFTR with the antibiotic streptomycin. As controls, they kept untreated mice, both mutant and normal.

Untreated CFTR-deficient mice had more bacterial growth in the gut compared to normal mice. The bacteria were mainly of different Lactobacillus types. Streptomycin reduced the overgrowth in the mutant mice to the same levels observed in the normal mice, whereas treatment did not affect the levels in the normal mice. The team also noticed that the levels of Lactobacillus species in the CFTR mutants were normalized after treatment.

Streptomycin treatment did not affect the levels of gut or bone disease in the mice, but, importantly, it reduced the levels of airway hyper-responsiveness. The team also performed correlation analyses, indicating that gut bacterial load weakly correlated with an increased airway resistance response, but the results were not statistically significant.

The study also reported that the CFTR-deficient mice had an altered immune profile, mainly characterized by abnormal levels of T cells producing the cytokine IL-17.

Streptomycin treatment did not affect the numbers of white blood cells in the lungs of either type of mice, but the researchers noticed that it decreased the amount of IL-17 producing T cells and caused an increase in other kinds of white blood cells.

This study was the first to show that the gut microbiome may influence airway mechanics in CF, offering new insights into CF pathology.