Impact of Altered Gut Microbiota and Its Metabolites in Cystic Fibrosis

Overview

Journal Metabolites

Publisher MDPI

Date 2021 Mar 6

PMID 33671639

Citations 30

Authors

Aravind Thavamani

Iman Salem

Thomas J Sferra

Senthilkumar Sankararaman

Affiliations

Soon will be listed here.

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.

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References

de Freitas M, Moreira E, Tomio C, Moreno Y, Daltoe F, Barbosa E . Altered intestinal microbiota composition, antibiotic therapy and intestinal inflammation in children and adolescents with cystic fibrosis. PLoS One. 2018; 13(6):e0198457. PMC: 6014676. DOI: 10.1371/journal.pone.0198457. View

Hoen A, Li J, Moulton L, OToole G, Housman M, Koestler D . Associations between Gut Microbial Colonization in Early Life and Respiratory Outcomes in Cystic Fibrosis. J Pediatr. 2015; 167(1):138-47.e1-3. PMC: 4674690. DOI: 10.1016/j.jpeds.2015.02.049. View

Madan J . Neonatal Gastrointestinal and Respiratory Microbiome in Cystic Fibrosis: Potential Interactions and Implications for Systemic Health. Clin Ther. 2016; 38(4):740-6. PMC: 5206974. DOI: 10.1016/j.clinthera.2016.02.008. View

Gelfond D, Ma C, Semler J, Borowitz D . Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig Dis Sci. 2012; 58(8):2275-81. DOI: 10.1007/s10620-012-2209-1. View

Li L, Somerset S . Associations between Flavonoid Intakes and Gut Microbiota in a Group of Adults with Cystic Fibrosis. Nutrients. 2018; 10(9). PMC: 6164979. DOI: 10.3390/nu10091264. View

Carmody R, Gerber G, Luevano Jr J, Gatti D, Somes L, Svenson K . Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe. 2014; 17(1):72-84. PMC: 4297240. DOI: 10.1016/j.chom.2014.11.010. View

Galloway-Pena J, Hanson B . Tools for Analysis of the Microbiome. Dig Dis Sci. 2020; 65(3):674-685. PMC: 7598837. DOI: 10.1007/s10620-020-06091-y. View

Dhaliwal J, Leach S, Katz T, Nahidi L, Pang T, Lee J . Intestinal inflammation and impact on growth in children with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2014; 60(4):521-6. DOI: 10.1097/MPG.0000000000000683. View

Scanlan P, Buckling A, Kong W, Wild Y, Lynch S, Harrison F . Gut dysbiosis in cystic fibrosis. J Cyst Fibros. 2012; 11(5):454-5. DOI: 10.1016/j.jcf.2012.03.007. View

10.

Garg M, Ooi C . The Enigmatic Gut in Cystic Fibrosis: Linking Inflammation, Dysbiosis, and the Increased Risk of Malignancy. Curr Gastroenterol Rep. 2017; 19(2):6. DOI: 10.1007/s11894-017-0546-0. View

11.

Werlin S, Benuri-Silbiger I, Kerem E, Adler S, Goldin E, Zimmerman J . Evidence of intestinal inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2010; 51(3):304-8. DOI: 10.1097/MPG.0b013e3181d1b013. View

12.

Francoise A, Hery-Arnaud G . The Microbiome in Cystic Fibrosis Pulmonary Disease. Genes (Basel). 2020; 11(5). PMC: 7288443. DOI: 10.3390/genes11050536. View

13.

Leung D, Yimlamai D . The intestinal microbiome and paediatric liver disease. Lancet Gastroenterol Hepatol. 2017; 2(6):446-455. DOI: 10.1016/S2468-1253(16)30241-2. View

14.

Li L, Somerset S . The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies. Clin Nutr. 2014; 33(4):571-80. DOI: 10.1016/j.clnu.2014.04.004. View

15.

Bazett M, Bergeron M, Haston C . Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model. Sci Rep. 2016; 6:19189. PMC: 4709690. DOI: 10.1038/srep19189. View

16.

Bilski J, Mazur-Bialy A, Wojcik D, Zahradnik-Bilska J, Brzozowski B, Magierowski M . The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract. Mediators Inflamm. 2017; 2017:9074601. PMC: 5339520. DOI: 10.1155/2017/9074601. View

17.

Da Silva H, Teterina A, Comelli E, Taibi A, Arendt B, Fischer S . Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. Sci Rep. 2018; 8(1):1466. PMC: 5780381. DOI: 10.1038/s41598-018-19753-9. View

18.

Wang B, Jiang X, Cao M, Ge J, Bao Q, Tang L . Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease. Sci Rep. 2016; 6:32002. PMC: 4994089. DOI: 10.1038/srep32002. View

19.

Vernocchi P, Del Chierico F, Russo A, Majo F, Rossitto M, Valerio M . Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype. PLoS One. 2018; 13(12):e0208171. PMC: 6283533. DOI: 10.1371/journal.pone.0208171. View

20.

Schippa S, Iebba V, Santangelo F, Gagliardi A, De Biase R, Stamato A . Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PLoS One. 2013; 8(4):e61176. PMC: 3629184. DOI: 10.1371/journal.pone.0061176. View