The Intestinal Microbiome and Cystic Fibrosis Transmembrane Conductance Regulator Modulators: Emerging Themes in the Management of Gastrointestinal Manifestations of Cystic Fibrosis

Karb, Daniel; Cummings, Linda C.

doi:10.1007/s11894-021-00817-2

Cited by 8 publications

(6 citation statements)

References 84 publications

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“…Patients with cystic fibrosis have traditionally been treated with laxatives to prevent recurrent obstructive episodes and with agents that inhibit acid secretion to mitigate reflux symptoms and optimize digestion. These suboptimal strategies to improve CF-associated intestinal disease are now being successfully replaced by CFTR targeted therapy which improves not only the pulmonary but also the intestinal symptoms [ 54 , 88 , 112 ]. Preliminary results suggest that this improvement is not reached via an alteration of the dysbiotic gut microbiota seen in patients with CF [ 108 ].…”

Section: Strategies To Influence Luminal Alkalinity In Patients With ...mentioning

confidence: 99%

Bicarbonate secretion and acid/base sensing by the intestine

Becker,

Seidler

2024

Pflugers Arch - Eur J Physiol

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The transport of bicarbonate across the enterocyte cell membrane regulates the intracellular as well as the luminal pH and is an essential part of directional fluid movement in the gut. Since the first description of “active” transport of HCO3− ions against a concentration gradient in the 1970s, the fundamental role of HCO3− transport for multiple intestinal functions has been recognized. The ion transport proteins have been identified and molecularly characterized, and knockout mouse models have given insight into their individual role in a variety of functions. This review describes the progress made in the last decade regarding novel techniques and new findings in the molecular regulation of intestinal HCO3− transport in the different segments of the gut. We discuss human diseases with defects in intestinal HCO3− secretion and potential treatment strategies to increase luminal alkalinity. In the last part of the review, the cellular and organismal mechanisms for acid/base sensing in the intestinal tract are highlighted.

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Section: Strategies To Influence Luminal Alkalinity In Patients With ...mentioning

confidence: 99%

Bicarbonate secretion and acid/base sensing by the intestine

Becker,

Seidler

2024

Pflugers Arch - Eur J Physiol

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“…Different studies have shown statistically significant improvements, not only in lung function and FEV1, but also in the BMI [ 165 , 166 ]. The fall in pulmonary exacerbations and the lower work of breathing lead to a reduction in the REE and in energy expenditure that enables weight gain and the changes in body composition, with an increase in both fat and lean mass [ 167 , 168 , 169 ].…”

Section: Intensified Feeding Interventionmentioning

confidence: 99%

Nutritional Care in Children with Cystic Fibrosis

et al. 2023

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Patients with cystic fibrosis (CF) are prone to malnutrition and growth failure, mostly due to malabsorption caused by the derangement in the chloride transport across epithelial surfaces. Thus, optimal nutritional care and support should be an integral part of the management of the disease, with the aim of ameliorating clinical outcomes and life expectancy. In this report, we analyzed the nutrition support across the different ages, in patients with CF, with a focus on the relationships with growth, nutritional status, disease outcomes and the use of the CF transmembrane conductance regulator (CFTR) modulators. The nutrition support goal in CF care should begin as early as possible after diagnosis and include the achievement of an optimal nutritional status to support the growth stages and puberty development in children, that will further support the maintenance of an optimal nutritional status in adult life. The cornerstone of nutrition in patients with CF is a high calorie, high-fat diet, in conjunction with a better control of malabsorption due to pancreatic enzyme replacement therapy, and attention to the adequate supplementation of fat-soluble vitamins. When the oral caloric intake is not enough for reaching the anthropometric nutritional goals, supplemental enteral feeding should be initiated to improve growth and the nutritional status. In the last decade, the therapeutic possibilities towards CF have grown in a consistent way. The positive effects of CFTR modulators on nutritional status mainly consist in the improvement in weight gain and BMI, both in children and adults, and in an amelioration in terms of the pulmonary function and reduction of exacerbations. Several challenges need to be overcome with the development of new drugs, to transform CF from a fatal disease to a treatable chronic disease with specialized multidisciplinary care.

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“…Importantly, CFTR protein function modulators have also shown promise in the treatment of CF-associated GI pathologies [ 142 , 143 , 144 , 145 ]. A key reagent for the preclinical testing of these drugs has been the development of patient-derived organoids from the colorectum [ 67 , 69 ].…”

Section: Targeting Specific Cftr Mutations With Modulator Drugs Impli...mentioning

confidence: 99%

CFTR and Gastrointestinal Cancers: An Update

Bhattacharya

Blankenheim

Scott

et al. 2022

JPM

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Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine.

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The Intestinal Microbiome and Cystic Fibrosis Transmembrane Conductance Regulator Modulators: Emerging Themes in the Management of Gastrointestinal Manifestations of Cystic Fibrosis

Cited by 8 publications

References 84 publications

Bicarbonate secretion and acid/base sensing by the intestine

Bicarbonate secretion and acid/base sensing by the intestine

Nutritional Care in Children with Cystic Fibrosis

CFTR and Gastrointestinal Cancers: An Update

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