Highly Effective Modulator Therapy: Implications for the Microbial Landscape in Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive multisystem disorder caused by mutations in the cystic fibrosis conductance regulator (CFTR) anion channel. In the lungs specifically, CFTR mutations lead to changes in mucus viscosity and defective mucociliary clearance. Moreover, people with CF (pwCF) mount an insufficient immune response to invading pathogens, which predisposes individuals to chronic airway disease associated with chronic inflammation, colonization, and recurrent infections by mainly opportunistic pathogens. These chronic infections in the CF lung are typically polymicrobial and frequently harbour multidrug-resistant pathogens, making both treatment and eradication very challenging. During the last decade, the development of highly effective CFTR modulator therapy (HEMT) has led to a breakthrough in treatment options for pwCF. While the majority of pwCF now live longer and have fewer CF exacerbations, colonisation with common respiratory pathogens persists, thereby contributing to chronic inflammation and infection. Interestingly, there are limited reports examining the lung microbiome in the post-modulator era. Since ETI treatment is still quite novel and has only been used for about five years by now, this review will be one of the first discussing the current literature on the effect of ETI on CF pathogens. In addition, we will identify unanswered questions that remain from the effect of HEMT on the CF microbiome.