Changes in fecal microbiota with CFTR modulator therapy: A pilot study

Ce, Pope; Vo, AT; Hs, Hayden; Weiss, Eli; Durfey, Samantha L; McNamara, Sharon; Ratjen, Anina; Grogan, Brenda; S, Carter; Nay, Laura; Parsek,; Pk, Singh; McKone, E.F.; Aitken, ML; Rosenfeld,; Lr, Hoffman

doi:10.1016/j.jcf.2020.12.002

Cited by 22 publications

(36 citation statements)

References 26 publications

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“…Pancreatic status is difficult to separate from CFTR genotype, as pancreatic status can be used as an indicator of CFTR dysfunctional severity ( 59 ). Of the few studies to examine the influence of pancreatic sufficiency on the intestinal microbiota, most have observed a modest influence ( 53 , 59 , 126 ). In a study by Nielsen et al, pwCF with pancreatic sufficiency trend toward higher alpha-diversity and have significant alterations in some taxa that are typically intermediate relative to the healthy and pancreatic insufficient CF cohorts.…”

Section: Drivers Of Microbiota Alterationsmentioning

confidence: 99%

“…Burke et al observed significant changes as well, but in different taxa; Ruminococcus and Anaerotruncus are increased in a pancreatic sufficient group compared to pancreatic insufficient pwCF ( 53 ). Pope et al found significant increases in Proteobacteria and Bacteroidetes and significantly decreased Actinobacteria in a pancreatic sufficient group ( 126 ). Of note, the milder mutations that lead to CF with pancreatic sufficiency are rarer than severe mutations, and the largest of these studies included only 12 individuals in the pancreatic sufficient group, which likely contributes to the lack of consistency and significant observable alterations.…”

Section: Drivers Of Microbiota Alterationsmentioning

confidence: 99%

“…Several studies have examined the impacts of modulator therapies on the airway microbiota, with apparently modest improvements in pathogen burden and changes in lung microbiota in some but not all studies ( 158 – 160 ). However, there are two studies to date that look specifically at the effects of modulators on the gut microbiota of both children and adults with CF ( 24 , 126 ). These studies examine the effects of ivacaftor and ivacaftor/lumacaftor.…”

Section: Remediating the Cf Microbiotamentioning

confidence: 99%

“…Ivacaftor treatment was shown to decrease fecal calprotectin in a small CF cohort, as well as to significantly increase the relative abundance of Akkermansia ( 24 ). An exploratory analysis by Pope et al examined changes in the intestinal microbiota of both pancreatic sufficient and insufficient patients upon initiation of ivacaftor and ivacaftor/lumacaftor, respectively ( 126 ). This study did not find any significant changes after modulator initiation for alpha-diversity, microbiota composition, or fecal fat in either group.…”

Section: Remediating the Cf Microbiotamentioning

confidence: 99%

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The Gut-Lung Axis in Cystic Fibrosis

Price

O’Toole

2021

J Bacteriol

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Cystic Fibrosis (CF) is a heritable, multi-organ disease that impacts all tissues that normally express CFTR protein. While importance of the airway microbiota has long been recognized, the intestinal microbiota has only recently been recognized as an important player in both intestinal and lung health outcomes for persons with CF (pwCF). Here, we summarize current literature related to the gut-lung axis in CF, with a particular focus on three key ideas: Mechanisms through which microbes influence the gut-lung axis, drivers of microbiota alterations, and the potential for intestinal microbiota remediation.

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Section: Drivers Of Microbiota Alterationsmentioning

confidence: 99%

Section: Drivers Of Microbiota Alterationsmentioning

confidence: 99%

Section: Remediating the Cf Microbiotamentioning

confidence: 99%

Section: Remediating the Cf Microbiotamentioning

confidence: 99%

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The Gut-Lung Axis in Cystic Fibrosis

Price

O’Toole

2021

J Bacteriol

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“…The few GI-specific studies to date have also been very limited in sample sizes and varied in their study populations. For example, Pope et al [197] did not observe any significant changes in the gut microbiota following the initiation of Ivacaftor or Lumacaftor/Ivacaftor, contrary to the aforementioned findings by Ooi et al [65] and Kristensen et al [196]. However, the study by Pope et al [197] involved a cohort of all PS patients with an R117H allele, whereas Ooi et al [65] included predominantly PI patients with a G551D mutation, and Kristensen et al [196] studied a cohort of primarily PI patients with an S1251N mutation.…”

Section: Cf Intestinal Disease In the Era Of Cftr Modulator Therapiesmentioning

confidence: 99%

Intestinal Inflammation and Alterations in the Gut Microbiota in Cystic Fibrosis: A Review of the Current Evidence, Pathophysiology and Future Directions

Tam

Dorst

McKay

et al. 2022

JCM

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Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disease. While its burden of morbidity and mortality is classically associated with pulmonary disease, CF also profoundly affects the gastrointestinal (GI) tract. Chronic low-grade inflammation and alterations to the gut microbiota are hallmarks of the CF intestine. The etiology of these manifestations is likely multifactorial, resulting from cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, a high-fat CF diet, and the use of antibiotics. There may also be a bidirectional pathophysiological link between intestinal inflammation and changes to the gut microbiome. Additionally, a growing body of evidence suggests that these GI manifestations may have significant clinical associations with growth and nutrition, quality of life, and respiratory function in CF. As such, the potential utility of GI therapies and long-term GI outcomes are areas of interest in CF. Further research involving microbial modulation and multi-omics techniques may reveal novel insights. This article provides an overview of the current evidence, pathophysiology, and future research and therapeutic considerations pertaining to intestinal inflammation and alterations in the gut microbiota in CF.

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Nutritional status in the era of highly effective CFTR modulators

Bass,

Alvarez

2024

Pediatric Pulmonology

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Advances in cystic fibrosis (CF) diagnostics and therapeutics have led to improved health and longevity, including increased body weight and decreased malnutrition in people with CF. Highly effective CFTR modulator therapies (HEMT) are associated with increased weight through a variety of mechanisms, accelerating trends of overweight and obesity in the CF population. Higher body mass index (BMI) is associated with improved pulmonary function in CF, yet the incremental improvement at overweight and obese BMIs is not clear. Improvements in pulmonary health with increasing BMI are largely driven by increases in fat‐free mass (FFM), and impact of HEMT on FFM is uncertain. While trends toward higher weight and BMI are generally seen as favorable in CF, the increased prevalence of overweight and obesity has raised concern for potential risk of traditional age‐ and obesity‐related comorbidities. Such comorbidities, including impaired glucose tolerance, hypertension, cardiac disease, hyperlipidemia, fatty liver, colon cancer, and obstructive sleep apnea, may occur on top of pre‐existing CF‐related comorbidities. CF nutrition recommendations are evolving in the post‐modulator era to more individualized approaches, in contrast to prior blanket high‐fat, high‐calorie prescriptions for all. Ultimately, it will be essential to redefine goals for optimal weight and nutritional status to allow for holistic health and aging in people with CF.

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Changes in fecal microbiota with CFTR modulator therapy: A pilot study

Cited by 22 publications

References 26 publications

The Gut-Lung Axis in Cystic Fibrosis

The Gut-Lung Axis in Cystic Fibrosis

Intestinal Inflammation and Alterations in the Gut Microbiota in Cystic Fibrosis: A Review of the Current Evidence, Pathophysiology and Future Directions

Nutritional status in the era of highly effective CFTR modulators

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