Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is the most common lethal, multisystemic genetic disorder in Caucasians. Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) protein are responsible for impairment of epithelial anionic transport, leading to impaired fluid regulation and pH imbalance across multiple organs. Gastrointestinal (GI) manifestations in CF may begin in utero and continue throughout the life, resulting in a chronic state of an altered intestinal milieu. Inherent dysfunction of CFTR leads to dysbiosis of the gut. This state of dysbiosis is further perpetuated by acquired factors such as use of antibiotics for recurrent pulmonary exacerbations. Since the gastrointestinal microbiome and their metabolites play a vital role in nutrition, metabolic, inflammatory, and immune functions, the gut dysbiosis will in turn impact various manifestations of CF-both GI and extra-GI. This review focuses on the consequences of gut dysbiosis and its metabolic implications on CF disease and possible ways to restore homeostasis.

Keywords: cystic fibrosis; diversity; dysbiosis; gut microbiota; metabolites; microbiome; probiotics.

Figure 1

Patterns of gut dysbiosis in cystic fibrosis and their impact on the disease manifestations (created with BioRender.com). (↓—decrease; ↑—increase; F. prausnitzii = Faecalibacterium prausnitzii; E. faecalis = Enterococcus faecalis; E. coli = Escherichia coli; GABA = gamma aminobutyric acid)

Figure 2

Functions of gut microbiota (Created with https://biorender.com/ (accessed on 18 February 2021)). (SCFAs = short-chain fatty acids).

Figure 3

Gut dysbiosis in cystic fibrosis and therapies that aim to modulate the dysbiosis.