Studies have demonstrated that people with CF with pancreatic insufficiency (PI) have fecal dysbioses. Evidence suggests the causes of these dysbioses are multifactorial, and that important drivers include antibiotic exposure, dietary intake, and CF gastrointestinal tract dysfunction, including nutrient malabsorption. In this pilot study, we tested whether initiation of the CFTR modulator treatments ivacaftor (in a cohort of pancreatic sufficient (PS) people with CF and an R117H CFTR variant) or lumacaftor/ivacaftor (in a cohort of PI people with CF and an F508del variant) changed fecal measures of malabsorption or fecal microbiomes. While we identified no statistically significant fecal changes with either treatment, we detected trends in the PI cohort when initiating lumacaftor/ivacaftor towards decreased fecal fat content and towards fecal microbiomes that more closely resembled the fecal microbiota of people without PI. While these findings support a model in which nutrient malabsorption resulting from CF-induced PI drives fecal dysbiosis, they must be validated in future, larger studies of fecal microbiome and malabsorption outcomes with highly effective CFTR modulator therapies.

研究表明，患有胰腺功能不全 (PI) 的 CF 患者存在粪便菌群失调。有证据表明，这些生态失调的原因是多因素的，重要的驱动因素包括抗生素暴露、饮食摄入和 CF 胃肠道功能障碍，包括营养吸收不良。在这项初步研究中，我们测试了是否启动 CFTR 调节剂治疗ivacaftor（在一组胰腺充足（PS）患有 CF 和 R117H CFTR 变体的人群中）或 lumacaftor/ivacaftor（在一组患有 CF 和 F508del 的 PI 人群中）变体）改变了吸收不良或粪便微生物组的粪便测量值。虽然我们发现两种治疗都没有统计学上显着的粪便变化，当开始使用 lumacaftor/ivacaftor 时，我们在 PI 队列中发现了降低粪便脂肪含量和更接近于没有 PI 的人的粪便微生物群的粪便微生物群的趋势。虽然这些发现支持了一个模型，其中 CF 诱导的 PI 导致的营养吸收不良会导致粪便生态失调，但它们必须在未来通过高效 CFTR 调节剂疗法对粪便微生物组和吸收不良结果进行更大规模的研究进行验证。