Changes in fecal lipidome after treatment with ivacaftor without changes in microbiome or bile acids

Rosara Bass; Ceylan Tanes; Kyle Bittinger; Yun Li; Hongzhe Lee; Elliot S Friedman; Imhoi Koo; Andrew D Patterson; Qing Liu; Gary D Wu; Virginia A Stallings

doi:10.1016/j.jcf.2023.09.010

Changes in fecal lipidome after treatment with ivacaftor without changes in microbiome or bile acids

J Cyst Fibros. 2023 Oct 7:S1569-1993(23)00915-3. doi: 10.1016/j.jcf.2023.09.010. Online ahead of print.

Authors

Rosara Bass¹, Ceylan Tanes², Kyle Bittinger², Yun Li³, Hongzhe Lee³, Elliot S Friedman⁴, Imhoi Koo⁵, Andrew D Patterson⁵, Qing Liu⁶, Gary D Wu⁴, Virginia A Stallings⁷

Affiliations

¹ Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA; Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA. Electronic address: bassr@chop.edu.
² Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.
³ Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Dr., Philadelphia, PA 19104, USA.
⁴ Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
⁵ Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 322 Life Sciences Building, University Park, PA 16802, USA.
⁶ Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
⁷ Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA; Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.

PMID: 37813785
PMCID: PMC10998923 (available on 2025-04-07)
DOI: 10.1016/j.jcf.2023.09.010

Abstract

Background: Alterations in gastrointestinal health are prominent manifestations of cystic fibrosis (CF) and can independently impact pulmonary function. Ivacaftor has been associated with robust improvements in pulmonary function and weight gain, but less is known about the impact of ivacaftor on the fecal microbiome, lipidome, and bile acids.

Methods: Stool samples from 18 patients with CF and gating mutations (ages 6-61 years, 13 pancreatic insufficient) were analyzed for fecal microbiome and lipidome composition as well as bile acid concentrations at baseline and after 3 months of treatment with ivacaftor. Microbiome composition was also assessed in a healthy reference cohort.

Results: Alpha and beta diversity of the microbiome were different between CF and reference cohort at baseline, but no treatment effect was seen in the CF cohort between baseline and 3 months. Seven lipids increased with treatment. No differences were seen in bile acid concentrations after treatment in CF. At baseline, 403 lipids and unconjugated bile acids were different between pancreatic insufficient (PI-CF) and sufficient (PS-CF) groups and 107 lipids were different between PI-CF and PS-CF after 3 months of treatment.

Conclusions: The composition and diversity of the fecal microbiome were different in CF as compared to a healthy reference, and did not change after 3 months of ivacaftor. We detected modest differences in the fecal lipidome with treatment. Differences in lipid and bile acid profiles between PS-CF and PI-CF were attenuated after 3 months of treatment.

Keywords: Bile acids; Cystic fibrosis; Intestine; Ivacaftor; Lipidome; Microbiome; Stool.

Abstract

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