Changes in Fecal Microbiota in Adults with Cystic Fibrosis with 6 Months of CFTR Modulator Therapy Elexacaftor/Tezacaftor/Ivacaftor (ETI)

Cystic fibrosis (CF) gastrointestinal (GI) disease carries a significant disease burden, inclusive of intestinal obstruction, pancreatic insufficiency, and CF hepatobiliary involvement. While the pathogenesis of these GI manifestations remains unknown, there is a postulated role for intestinal inflammation in driving CF GI disease. People with CF often have fecal dysbioses relative to healthy individuals without CF characterized by increased abundances of pro-inflammatory microbiota correlating with increased fecal measures of inflammation as measured by fecal calprotectin. Findings from the prospective, multi-center observational PROMISE study showed that treatment with the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) is followed by a decrease in fecal calprotectin. However, it is unknown how ETI changes the composition of the fecal microbiota and how such changes relate to fecal calprotectin, which is critical to understanding the pathogenesis of CF related GI disease. We analyzed fecal samples from PROMISE to define the relationships between dysbiosis and inflammatory measures before and after ETI.