Changes in Fecal Microbiota with CFTR Modulator Therapy: A Pilot Study

Overview

Journal J Cyst Fibros

Publisher Elsevier

Specialty Pulmonary Medicine

Date 2021 Jan 4

PMID 33390317

Citations 12

Authors

C E Pope

A T Vo

H S Hayden

E J Weiss

S Durfey

S McNamara

A Ratjen

B Grogan

S Carter

L Nay

M R Parsek

P K Singh

E F McKone

M L Aitken

M R Rosenfeld

L R Hoffman

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Longitudinal profiling of the intestinal microbiome in children with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

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

Bass R, Tanes C, Bittinger K, Li Y, Lee H, Friedman E J Cyst Fibros. 2023; 23(3):481-489.

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The gut-lung axis in the CFTR modulator era.

Lussac-Sorton F, Charpentier E, Imbert S, Lefranc M, Bui S, Fayon M Front Cell Infect Microbiol. 2023; 13:1271117.

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Tezacaftor/Ivacaftor therapy has negligible effects on the cystic fibrosis gut microbiome.

Marsh R, Santos C, Hanson L, Ng C, Major G, Smyth A Microbiol Spectr. 2023; :e0117523.

PMID: 37607068 PMC: 10581179. DOI: 10.1128/spectrum.01175-23.

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