Abstract

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Next to progressive airway disease, CF is also associated with intestinal inflammation and dysbiosis. Ivacaftor, a CFTR potentiator, has improved pulmonary and nutritional status but its effects on the intestinal microbiota and inflammation are unclear. Hence, we assessed the changes on the intestinal microbial communities (16S rRNA variable 3 gene region) and inflammatory markers (calprotectin and M2-pyruvate kinase [M2-PK]) in 16 CF individuals (8 children and 8 adults) before and after (median 6.1 months) ivacaftor. Stool calprotectin significantly decreased following ivacaftor (median [IQR]: 154.4 [102.1–284.2] vs. 87.5 [19.5–190.2] mg/kg, P = 0.03). There was a significant increase in Akkermansia with ivacaftor. Increased abundance of Akkermansia was associated with normal stool M2-PK concentrations, and decreased abundances of Enterobacteriaceae correlated with decreased stool calprotectin concentrations. In summary, changes in the gut microbiome and decrease in intestinal inflammation was associated with Ivacaftor treatment among individuals with CF carrying at least one gating CFTR mutation. Thus, CFTR-modifying therapy may adequately improve the aberrant pathophysiology and milieu of the CF gut to favor a more healthy microbiota, which in turn reduces intestinal inflammation.

Details

Title
Impact of CFTR modulation with Ivacaftor on Gut Microbiota and Intestinal Inflammation
Author
Ooi, Chee Y 1   VIAFID ORCID Logo  ; Syed, Saad A 2 ; Rossi, Laura 2 ; Garg, Millie 3 ; Needham, Bronwen 3   VIAFID ORCID Logo  ; Avolio, Julie 4 ; Young, Kelsey 4 ; Surette, Michael G 2 ; Gonska, Tanja 5 

1  School of Women’s and Children’s Health, Medicine, The University of New South Wales, Sydney, NSW, Australia; Molecular and Integrative Cystic Fibrosis (miCF) Research Centre, Sydney Children’s Hospital, Randwick, NSW, Australia; Department of Gastroenterology, Sydney Children’s Hospital, Randwick, NSW, Australia 
2  Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada 
3  School of Women’s and Children’s Health, Medicine, The University of New South Wales, Sydney, NSW, Australia 
4  Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada 
5  Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada; Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada 
Pages
1-8
Publication year
2018
Publication date
Dec 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-36364-6
ProQuest document ID
2155897864
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.