Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2020 Jan 22;1(1):CD012949.
doi: 10.1002/14651858.CD012949.pub2.

Probiotics for people with cystic fibrosis

Michael J Coffey  1   2 , Millie Garg  1 , Nusrat Homaira  1   3 , Adam Jaffe  1   3 , Chee Y Ooi  1   4
Affiliations
Meta-Analysis

Probiotics for people with cystic fibrosis

Michael J Coffey et al. Cochrane Database Syst Rev. .

Abstract

Background: Cystic fibrosis (CF) is a multisystem disease and the importance of growth and nutrition has been well established, given its implications for lung function and overall survival. It has been established that intestinal dysbiosis (i.e. microbial imbalance) and inflammation is present in people with CF. Probiotics are commercially available (over-the-counter) and may improve both intestinal and overall health.

Objectives: To assess the efficacy and safety of probiotics for improving health outcomes in children and adults with CF.

Search methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last register search: 20 January 2020. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 29 January 2019.

Selection criteria: Randomised or quasi-randomised controlled trials (RCTs) assessing efficacies and safety of probiotics in children and adults with CF. Cross-over RCTs with a washout phase were included and for those without a washout period, only the first phase of each trial was analysed.

Data collection and analysis: We independently extracted data and assessed the risk of bias of the included trials; we used GRADE to assess the certainty of the evidence. We contacted trial authors for additional data. Meta-analyses were undertaken on outcomes at several time points.

Main results: We identified 17 trials and included 12 RCTs (11 completed and one trial protocol - this trial was terminated early) (464 participants). Eight trials included only children, whilst four trials included both children and adults. Trial duration ranged from one to 12 months. Nine trials compared a probiotic (seven single strain and three multistrain preparations) with a placebo preparation, two trials compared a synbiotic (multistrain) with a placebo preparation and one trial compared two probiotic preparations. Overall we judged the risk of bias in the 12 trials to be low. Three trials had a high risk of performance bias, two trials a high risk of attrition bias and six trials a high risk of reporting bias. Only two trials were judged to have low or unclear risk of bias for all domains. Four trials were sponsored by grants only, two trials by industry only, two trials by both grants and industry and three trials had an unknown funding source. Combined data from four trials (225 participants) suggested probiotics may reduce the number of pulmonary exacerbations during a four to 12 month time-frame, mean difference (MD) -0.32 episodes per participant (95% confidence interval (CI) -0.68 to 0.03; P = 0.07) (low-certainty evidence); however, the 95% CI includes the possibility of both an increased and a reduced number of exacerbations. Additionally, two trials (127 participants) found no evidence of an effect on the duration of antibiotic therapy during the same time period. Combined data from four trials (177 participants) demonstrated probiotics may reduce faecal calprotectin, MD -47.4 µg/g (95% CI -93.28 to -1.54; P = 0.04) (low-certainty evidence), but the results for other biomarkers mainly did not show any difference between probiotics and placebo. Two trials (91 participants) found no evidence of effect on height, weight or body mass index (low-certainty evidence). Combined data from five trials (284 participants) suggested there was no difference in lung function (forced expiratory volume at one second (FEV1) % predicted) during a three- to 12-month time frame, MD 1.36% (95% CI -1.20 to 3.91; P = 0.30) (low-certainty evidence). Combined data from two trials (115 participants) suggested there was no difference in hospitalisation rates during a three- to 12-month time frame, MD -0.44 admissions per participant (95% CI -1.41 to 0.54; P = 0.38) (low-certainty evidence). One trial (37 participants) reported health-related quality of life and while the parent report favoured probiotics, SMD 0.87 (95% CI 0.19 to 1.55) the child self-report did not identify any effect, SMD 0.59 (95% CI -0.07 to 1.26) (low-certainty evidence). There were limited results for gastrointestinal symptoms and intestinal microbial profile which were not analysable. Only four trials and one trial protocol (298 participants) reported adverse events as a priori hypotheses. No trials reported any deaths. One terminated trial (12 participants and available as a protocol only) reported a severe allergic reaction (severe urticaria) for one participant in the probiotic group. Two trials reported a single adverse event each (vomiting in one child and diarrhoea in one child). The estimated number needed to harm for any adverse reaction (serious or not) is 52 people (low-certainty evidence).

Authors' conclusions: Probiotics significantly reduce faecal calprotectin (a marker of intestinal inflammation) in children and adults with CF, however the clinical implications of this require further investigation. Probiotics may make little or no difference to pulmonary exacerbation rates, however, further evidence is required before firm conclusions can be made. Probiotics are associated with a small number of adverse events including vomiting, diarrhoea and allergic reactions. In children and adults with CF, probiotics may be considered by patients and their healthcare providers. Given the variability of probiotic composition and dosage, further adequately-powered multicentre RCTs of at least 12 months duration are required to best assess the efficacy and safety of probiotics for children and adults with CF.

PubMed Disclaimer

Conflict of interest statement

Drs Chee Y. Ooi, Michael J. Coffey and Adam Jaffe are conducting an international, multicentre, double‐blind, randomised, placebo‐controlled trial on probiotics for infants and children with cystic fibrosis (Australian and New Zealand Clinical Trials Registry Number: ACTRN12616000797471).

Dr Chee Y. Ooi is a consultant for Vertex Pharmaceuticals Incorporated and a member of the advisory board for Evolution Health. Dr Adam Jaffe has received funding from Vertex Pharmaceuticals for membership to a medical advisory committee and an honorarium to host an educational event.

Millie Garg and Dr Nusrat Homaira have no known conflicts.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012949

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Bruzzese 2007 {published data only (unpublished sought but not used)}
    1. Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, Marco G, Maiuri L, et al. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clinical Nutrition (Edinburgh, Scotland) 2007;26(3):322‐8. [CFGD Register: GN115a] - PubMed
    1. Guarino A, Giannattasio A. Probiotics in cystic fibrosis: help from old friends. Pediatric Pulmonology 2008;43 Suppl 31:130. [CFGD Register: GN115b]
Bruzzese 2014 {published data only (unpublished sought but not used)}
    1. Bruzzese E, Callegari ML, Raia V, Viscovo S, Scotto R, Ferrari S, et al. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial. PloS one 2014;9(2):e87796. [CFGD Register: GN115c] - PMC - PubMed
    1. EUCTR2009‐011289‐27‐IT. Probiotics in Cystic Fibrosis ‐ ND. apps.who.int/trialsearch/Trial3.aspx?trialid=EUCTR2009‐011289‐27‐IT (date of registration 27 April 2009).
    1. NCT01961661. Probiotics on intestinal inflammation in cystic fibrosis [Effect of probiotics on intestinal inflammation and microflora in cystic fibrosis: a pilot study]. clinicaltrials.gov/ct2/show/NCT01961661 (first posted 11 October 2013).
Bruzzese 2018 {published data only (unpublished sought but not used)}
    1. Bruzzese E, Raia V, Ruberto E, Scotto R, Giannattasio A, Bruzzese D, et al. Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: a randomised placebo controlled trial. Journal of Cystic Fibrosis 2018;17(3):375‐82. [CFGD Register: GN267; DOI: 10.1016/j.jcf.2017.10.014] - DOI - PubMed
    1. NCT01956916. Probiotics in cystic fibrosis [Effects of LGG administration in children with cystic fibrosis: a randomized controlled trial]. clinicaltrials.gov/ct2/show/NCT01956916 (first posted 8 October 2013).
de Freitas 2018a {published data only}
    1. Freitas MB, Moreira EA, Oliveira DL, Tomio C, Rosa JS, Moreno YM, et al. Effect of synbiotic supplementation in children and adolescents with cystic fibrosis: a randomized controlled clinical trial. European Journal of Clinical Nutrition 2018;72(5):736‐43. [PUBMED: 29277839] - PubMed
del Campo 2009 {published data only}
    1. Campo R, Garriga M, Agrimbau J, Lamas A, Maiz L, Canton, et al. Improvement of intestinal comfort in cystic fibrosis patients after probiotics consumption. Journal of Cystic Fibrosis 2009;8 Suppl 2:S789. [Abstract no: 356; CFGD Register: GN226a]
del Campo 2014 {published data only (unpublished sought but not used)}
    1. Garriga M, Blas A, Burreros M, Guallarte P, Perez‐Aragon A, Lamas A, et al. Probiotic intake improves the gastrointestinal health of cystic fibrosis patients. Journal of Cystic Fibrosis 2013;12 Suppl 1:S6. [Abstract no.: WS3.6; CFGD Register: GN243b]
    1. Campo R, Garriga M, Perez‐Aragon A, Guallarte P, Lamas A, Maiz L, et al. Improvement of digestive health and reduction in proteobacterial populations in the gut microbiota of cystic fibrosis patients using a Lactobacillus reuteri probiotic preparation: a double blind prospective study. Journal of Cystic Fibrosis 2014;13(6):716‐22. [CFGD Register: GN243a] - PubMed
Di Benedetto 1998 {published data only (unpublished sought but not used)}
    1. Benedetto L, Raia V, Pastore A, Albano F, Spagnuolo MI, Vizia B, et al. Lactobacillus casei strain GG as adjunctive treatment to children with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 1998;26(5):542. [CFGD Register: GN268]
Di Nardo 2014 {published data only}
    1. Nardo G, Oliva S, Menichella A, Pistelli R, Biase RV, Patriarchi F, et al. Lactobacillus reuteri ATCC55730 in cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2014;58(1):81‐6. [CFGD Register: GN244] - PubMed
    1. NCT01737983. Effect of Lactobacillus reuteri in cystic fibrosis [Lactobacillus reuteri reduces pulmonary exacerbations and upper respiratory tract infections in CF patients with mild‐to‐moderate lung disease. LR administration might have a beneficial effect on the disease course of cystic fibrosis.]. clinicaltrials.gov/ct2/show/NCT01737983 (first posted 30 November 2012).
Fallahi 2013 {published data only}
    1. Fallahi G, Motamed F, Yousefi A, Shafieyoun A, Najafi M, Khodadad A, et al. The effect of probiotics on fecal calprotectin in patients with cystic fibrosis. Turkish Journal of Pediatrics 2013;55(5):475‐8. [CFGD Register: GN248] - PubMed
    1. Yousefi A, Shafieyoun A, Fallahi G, Rezaei N. Probiotics on fecal calprotectin of cystic fibrosis. Reply. Turkish Journal of Pediatrics 2014;56(3):333. - PubMed
Jafari 2013 {published data only}
    1. Jafari SA, Mehdizadeh‐Hakkak A, Kianifar HR, Hebrani P, Ahanchian H, Abbasnejad E. Effects of probiotics on quality of life in children with cystic fibrosis; a randomized controlled trial. Iranian Journal of Pediatrics 2013;23(6):669‐74. [CFGD Register: GN269] - PMC - PubMed
NCT01201434 {published and unpublished data}
    1. NCT01201434. Effect of probiotics on sputum inflammation and pulmonary infections in patients with cystic fibrosis [The effect of probiotics on sputum bacteria, sputum inflammation, and pulmonary infections in patients with cystic fibrosis: a double‐blind placebo‐controlled trial]. clinicaltrials.gov/ct2/show/NCT01201434 (first posted 14 September 2010).
Van Biervliet 2018 {published and unpublished data}
    1. Biervliet S, Hauser B, Verhulst S, Stepman H, Delanghe J, Warzee JP, et al. Probiotics in cystic fibrosis (CF) patients: a double blind cross‐over placebo controlled study. Pilot study from the ESPGHAN Working Group on Pancreas/CF. Clinical Nutrition ESPEN 2018;27:59‐65. [CFGD Register: GN266b] - PubMed
    1. Biervliet S, Hauser B, Verhulst S, Stepman H, Delanghe J, Warzee JP, et al. Probiotics in cystic fibrosis (CF) patients: a double blind cross‐over study. Journal of Cystic Fibrosis 2017;16 Suppl 1:S42. [CFGD Register: GN266a]

References to studies excluded from this review

Bruzzese 2004 {published data only}
    1. Bruzzese E, Raia V, Gaudiello G, Polito G, Buccigrossi V, Formicola V, et al. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Alimentary Pharmacology & Therapeutics 2004;20(7):813‐9. [DOI: 10.1111/j.1365-2036.2004.02174.x] - DOI - PubMed

References to studies awaiting assessment

IRCT201201258778N3 {published data only}
    1. IRCT201201258778N3. Effect of probiotics on intestinal inflammation in CF patients whit age more than 4 years [Effect of probiotics on intestinal inflammation in CF patients whit age more than 4 years based on fecal calportectine a double blind clinical trial]. https://en.irct.ir/trial/9275 (first received 12 March 2012). [CFGD Register: GN279; WHO ICTRP: www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201201258778N3]
IRCT201205219823N1 {published data only}
    1. IRCT201205219823N1. Probiotic effect on growth and quality of life in children with cystic fibrosis. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT201205219823N1 (first received 25 July 2012). [CFGD Register: GN280]

References to ongoing studies

ACTRN12616000797471 {published data only}
    1. ACTRN12616000797471. Probiotics and the EARly Life effects on intestinal bacteria and inflammation in children with Cystic Fibrosis (“PEARL‐CF”). www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370881 (first posted 17 June 2016).
IRCT2017011732004N1 {published data only}
    1. IRCT2017011732004N1. Effect of synbiotic supplementation in comparison with placebo on anthropometric indices, quality of life and clinical outcome in children with cystic fibrosis. en.irct.ir/trial/25032 (first posted 14 February 2017).
NCT01837355 {published data only}
    1. NCT01837355. Modulation of intestinal and pulmonary inflammation by lactobacillus diet supplementation in pediatric cystic fibrosis (MoHuM‐1). clinicaltrials.gov/ct2/show/NCT01837355 (first posted 23 April 2013).
RBR‐5byrsc {published data only}
    1. RBR‐5byrsc, Universidade Federal de Santa Catarina ‐ Florianópolis, S. C. Brazil, Universidade Federal de Santa Catarina ‐ Florianópolis, S. C. Brazil, Universidade Federal de Santa Catarina ‐ Florianópolis, S. C. Brazil. Effect of supplementation with a synbiotic on markers of the inflammatory response in children and adolescents with cystic fibrosis. apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR‐5byrsc (first posted 11 March 2016).

Additional references

Anathan 2016
    1. Ananthan A, Balasubramanian H, Rao S, Patole S. Probiotic supplementation in children with cystic fibrosis‐a systematic review. European Journal of Pediatrics 2016;175(10):1255‐66. - PubMed
Anderson 2017
    1. Anderson JL, Miles C, Tierney AC. Effect of probiotics on respiratory, gastrointestinal and nutritional outcomes in patients with cystic fibrosis: a systematic review. Journal of Cystic Fibrosis 2017;16(2):186‐97. - PubMed
Antosca 2019
    1. Antosca KM, Chernikova DA, Price CE, Ruoff KL, Li K, Guill MF, et al. Altered stool microbiota of infants with cystic fibrosis shows a reduction in genera associated with immune programming from birth. Journal of Bacteriology 2019;201(16):pii: e00274‐19. [DOI: 10.1128/JB.00274-19; PUBMED: 31209076] - DOI - PMC - PubMed
Arrieta 2014
    1. Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Frontiers in Immunology 2014;5:427. [PUBMED: 25250028] - PMC - PubMed
Burke 2017
    1. Burke DG, Fouhy F, Harrison MJ, Rea MC, Cotter PD, O'Sullivan O, et al. The altered gut microbiota in adults with cystic fibrosis. BMC Microbiology 2017;17(1):58. [PUBMED: 28279152] - PMC - PubMed
CF Foundation 2017
    1. CF Foundation. About cystic fibrosis. www.cff.org/What‐is‐CF/About‐Cystic‐Fibrosis (accessed 09 June 2017).
Corey 1988
    1. Corey M, McLaughlin FJ, Williams M, Levison H. A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. Journal of Clinical Epidemiology 1988;41(6):583‐91. [PUBMED: 3260274] - PubMed
Covidence 2019 [Computer program]
    1. Veritas Health Innovation. Covidence. Melbourne, Australia: Veritas Health Innovation, accessed 30 January 2019.
de Clercq 2017
    1. Clercq N, Frissen MN, Groen AK, Nieuwdorp M. Gut microbiota and the gut‐brain axis: new insights in the pathophysiology of metabolic syndrome. Psychosomatic Medicine 2017;79(8):874‐9. [DOI: 10.1097/PSY.0000000000000495; PUBMED: 28557822] - DOI - PubMed
de Freitas 2018b
    1. Freitas MB, Moreira EA, Tomio C, Moreno YM, Daltoe FP, Barbosa E, et al. Altered intestinal microbiota composition, antibiotic therapy and intestinal inflammation in children and adolescents with cystic fibrosis. PloS One 2018;13(6):e0198457. [PUBMED: 29933382] - PMC - PubMed
Debyser 2016
    1. Debyser G, Mesuere B, Clement L, Weygaert J, Hecke P, Duytschaever G, et al. Faecal proteomics: a tool to investigate dysbiosis and inflammation in patients with cystic fibrosis. Journal of Cystic Fibrosis 2016;15(2):242‐50. [PUBMED: 26330184] - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JP, Altman DG, editor(s) on behalf of the CSMG. Chapter 9: Analysing data and undertaking meta‐analysis. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Derwa 2017
    1. Derwa Y, Gracie DJ, Hamlin PJ, Ford AC. Systematic review with meta‐analysis: the efficacy of probiotics in inflammatory bowel disease. Alimentary Pharmacology & Therapeutics 2017;46(4):389‐400. [PUBMED: 28653751] - PubMed
Dhaliwal 2015
    1. Dhaliwal J, Leach S, Katz T, Nahidi L, Pang T, Lee JM, et al. Intestinal inflammation and impact on growth in children with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2015;60(4):521‐6. - PubMed
Duytschaever 2011
    1. Duytschaever G, Huys G, Bekaert M, Boulanger L, Boeck K, Vandamme P. Cross‐sectional and longitudinal comparisons of the predominant fecal microbiota compositions of a group of pediatric patients with cystic fibrosis and their healthy siblings. Applied and Environmental Microbiology 2011;77(22):8015‐24. [PUBMED: 21926193] - PMC - PubMed
Faith 2013
    1. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, et al. The long‐term stability of the human gut microbiota. Science (New York, N.Y.) 2013;341(6141):1237439. [PUBMED: 23828941] - PMC - PubMed
FAO/WHO 2002
    1. Food, Agriculture Organization of the United Nations. World Health Organization. Guidelines for the evaluation of probiotics in food: report of a joint FAO/WHO Working Group on drafting guidelines for the evaluation of probiotics in food. 2002. http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf (accessed prior to 25 September 2017). [FAO/WHO 2002]
Farrell 2008
    1. Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation Consensus Report. Journal of Pediatrics 2008;153(2):S4‐S14. - PMC - PubMed
Fouhy 2017
    1. Fouhy F, Ronan NJ, O'Sullivan O, McCarthy Y, Walsh AM, Murphy DM, et al. A pilot study demonstrating the altered gut microbiota functionality in stable adults with Cystic Fibrosis. Scientific Reports 2017;7(1):6685. [PUBMED: 28751714] - PMC - PubMed
Fuchs 1994
    1. Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. New England Journal of Medicine 1994;331(10):637‐42. - PubMed
Garg 2017
    1. Garg M, Leach ST, Coffey MJ, Katz T, Strachan R, Pang T, et al. Age‐dependent variation of fecal calprotectin in cystic fibrosis and healthy children. Journal of Cystic Fibrosis 2017;16(5):631‐6. [PUBMED: 28416415] - PubMed
Garg 2018
    1. Garg M, Leach ST, Pang T, Needham B, Coffey MJ, Katz T, et al. Age‐related levels of fecal M2‐pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10 years old. Journal of Cystic Fibrosis 2018;17(1):109‐13. [PUBMED: 28754328] - PubMed
Gibson 2017
    1. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature reviews. Gastroenterology & hepatology 2017;14(8):491‐502. [PUBMED: 28611480] - PubMed
Goldenberg 2013
    1. Goldenberg JZ, Ma SS, Saxton JD, Martzen MR, Vandvik PO, Thorlund K, et al. Probiotics for the prevention of Clostridium difficile‐associated diarrhea in adults and children. Cochrane Database of Systematic Reviews 2013, Issue 5. [DOI: 10.1002/14651858.CD006095.pub3; PUBMED: 23728658] - DOI - PubMed
Goldenberg 2015
    1. Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic‐associated diarrhea. Cochrane Database of Systematic Reviews 2015, Issue 12. [DOI: 10.1002/14651858.CD004827.pub4; PUBMED: 26695080] - DOI - PubMed
Hao 2015
    1. Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database of Systematic Reviews 2015, Issue 2. [DOI: 10.1002/14651858.CD006895.pub3; PUBMED: 25927096] - DOI - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011a
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2011b
    1. Higgins JP, Altman DG, Sterne JA, editor(s) on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2011c
    1. Higgins JP, Deeks JJ, Altman DG, editor(s), on behalf of the CSMG. Chapter 16: Special topics in statistics. In: Higgins JP, Green S, editor(s). Cochrane Handbook of Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hoen 2015
    1. Hoen AG, Li J, Moulton LA, O'Toole GA, Housman ML, Koestler DC, et al. Associations between gut microbial colonization in early life and respiratory outcomes in cystic fibrosis. Journal of Pediatrics 2015;167(1):138‐47.e1‐3. [PUBMED: 25818499] - PMC - PubMed
Jadin 2011
    1. Jadin SA, Wu GS, Zhang Z, Shoff SM, Tippets BM, Farrell PM, et al. Growth and pulmonary outcomes during the first 2 y of life of breastfed and formula‐fed infants diagnosed with cystic fibrosis through the Wisconsin Routine Newborn Screening Program. American Journal of Clinical Nutrition 2011;93(5):1038‐47. [PUBMED: 21430114] - PMC - PubMed
Kaakoush 2016
    1. Kaakoush NO, Pickford R, Jaffe A, Ooi CY. Is there a role for stool metabolomics in cystic fibrosis?. Pediatrics International : Official Journal of the Japan Pediatric Society 2016;58(8):808‐11. - PubMed
Lee 2012
    1. Lee JM, Leach ST, Katz T, Day AS, Jaffe A, Ooi CY. Update of faecal markers of inflammation in children with cystic fibrosis. Mediators of Inflammation 2012;2012:948367. [PUBMED: 22988347] - PMC - PubMed
Li 2014
    1. Li L, Somerset S. The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies. Clinical Nutrition (Edinburgh, Scotland) 2014;33(4):571‐80. [PUBMED: 24767984] - PubMed
Madan 2012
    1. Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, et al. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. mBio 2012;3(4):e00251‐12. [PUBMED: 22911969] - PMC - PubMed
Marsland 2015
    1. Marsland BJ, Trompette A, Gollwitzer ES. The gut‐lung axis in respiratory disease. Annals of the American Thoracic Society 2015;12 Suppl 2:S150‐6. [PUBMED: 26595731] - PubMed
McCormick 2010
    1. McCormick J, Mehta G, Olesen HV, Viviani L, Macek M Jr, Mehta A. Comparative demographics of the European cystic fibrosis population: a cross‐sectional database analysis. Lancet 2010;375(9719):1007‐13. [PUBMED: 20304245] - PubMed
Metchnikoff 1908
    1. Metchnikoff E. The prolongation of life; optimistic studies. New York & London: G. P. Putnam's Sons, 1908.
Neri 2019
    1. Neri LC, Taminato M, Filho LV. A systematic review of probiotics for cystic fibrosis patients: moving forward. Journal of Pediatric Gastroenterology and Nutrition 2019;68(3):394‐99. [DOI: 10.1097/MPG.0000000000002185; PUBMED: 30358738] - DOI - PubMed
Nielsen 2016
    1. Nielsen S, Needham B, Leach ST, Day AS, Jaffe A, Thomas T, et al. Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis. Scientific Reports 2016;6:24857. [DOI: 10.1038/srep24857] - DOI - PMC - PubMed
Nikniaz 2017
    1. Nikniaz Z, Nikniaz L, Bilan N, Somi MH, Faramarzi E. Does probiotic supplementation affect pulmonary exacerbation and intestinal inflammation in cystic fibrosis: a systematic review of randomized clinical trials. World Journal of Pediatrics 2017;13(4):307‐13. [DOI: 10.1007/s12519-017-0033-6; PUBMED: 28470579] - DOI - PubMed
Ooi 2015a
    1. Ooi CY, Pang T, Leach ST, Katz T, Day AS, Jaffe A. Fecal human beta‐defensin 2 in children with cystic fibrosis: is there a diminished intestinal innate immune response?. Digestive Diseases and Sciences 2015;60(10):2946‐52. - PubMed
Ooi 2018
    1. Ooi CY, Syed SA, Rossi L, Garg M, Needham B, Avolio J, et al. Impact of CFTR modulation with ivacaftor on gut microbiota and intestinal inflammation. Scientific Reports 2018;8(1):17834. [PUBMED: 30546102] - PMC - PubMed
Pang 2015
    1. Pang T, Leach ST, Katz T, Jaffe A, Day AS, Ooi CY. Elevated fecal M2‐pyruvate kinase in children with cystic fibrosis: a clue to the increased risk of intestinal malignancy in adulthood?. Journal of Gastroenterology and Hepatology 2015;30(5):866‐71. - PubMed
Plaza‐Diaz 2017
    1. Plaza‐Diaz J, Ruiz‐Ojeda FJ, Vilchez‐Padial LM, Gil A. Evidence of the anti‐inflammatory effects of probiotics and synbiotics in intestinal chronic diseases. Nutrients 2017;9(6):pii: E555. [DOI: 10.3390/nu9060555; PUBMED: 28555037] - DOI - PMC - PubMed
Quigley 2013
    1. Quigley EM. Gut bacteria in health and disease. Gastroenterology and Hepatology 2013;9(9):560‐9. [PUBMED: 24729765] - PMC - PubMed
Quittner 2009
    1. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire‐Revised Respiratory Symptom Scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest 2009;135(6):1610‐8. - PMC - PubMed
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rogers 2016
    1. Rogers GB, Narkewicz MR, Hoffman LR. The CF gastrointestinal microbiome: structure and clinical impact. Pediatric Pulmonology 2016;51 Suppl 44:S35‐44. [PUBMED: 27662102] - PMC - PubMed
Sanders 2019
    1. Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nature Reviews. Gastroenterology & Hepatology 2019 Jul 11 [Epub ahead of print]. [DOI: 10.1038/s41575-019-0173-3; PUBMED: 31296969] - DOI - PubMed
Schippa 2013
    1. Schippa S, Iebba V, Santangelo F, Gagliardi A, Biase RV, Stamato A, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PloS one 2013;8(4):e61176. [PUBMED: 23613805] - PMC - PubMed
Schünemann 2011a
    1. Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH on behalf of the CA and RMG and the CSMG. Chapter 11: Presenting results and ‘Summary of findings’ tables. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Shoff 2006
    1. Shoff SM, Ahn HY, Davis L, Lai H. Temporal associations among energy intake, plasma linoleic acid, and growth improvement in response to treatment initiation after diagnosis of cystic fibrosis. Pediatrics 2006;117(2):391‐400. [PUBMED: 16452358] - PubMed
Smyth 2000
    1. Smyth RL, Croft NM, O'Hea U, Marshall TG, Ferguson A. Intestinal inflammation in cystic fibrosis. Archives of Disease in Childhood 2000;82(5):394‐9. [PUBMED: 10799435] - PMC - PubMed
Sterne 2011
    1. Sterne JA, Egger M, Moher D, editor(s), on behalf of the CBMG. Chapter 10: Addressing reporting biases. In: Higgins JP, Green S, editor(s). Cochrane Handbook forSystematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Sullivan 2015
    1. Sullivan JS, Hounchell J, Pecott‐Grimm H, Cowan K, Lahiri T. Probiotic use and antibiotic associated gastrointestinal symptoms in pediatric patients with cystic fibrosis. Pediatric Pulmonology 2015;50 Suppl 41:407. [Abstract no.: 567]
Sutherland 2018
    1. Sutherland R, Katz T, Liu V, Quintano J, Brunner R, Tong CW, et al. Dietary intake of energy‐dense, nutrient‐poor and nutrient‐dense food sources in children with cystic fibrosis. Journal of Cystic Fibrosis 2018;17(6):804‐10. [PUBMED: 29724576] - PubMed
Tabori 2017
    1. Tabori H, Arnold C, Jaudszus A, Mentzel HJ, Renz DM, Reinsch S, et al. Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings. PLoS ONE 2017;12(5):e0174463. [PUBMED: 28472055] - PMC - PubMed
Tomas 2016
    1. Tomas J, Mulet C, Saffarian A, Cavin JB, Ducroc R, Regnault B, et al. High‐fat diet modifies the PPAR‐gamma pathway leading to disruption of microbial and physiological ecosystem in murine small intestine. Proceedings of the National Academy of Sciences of the United States of America 2016;113(40):E5934‐43. [PUBMED: 27638207] - PMC - PubMed
Turck 2016
    1. Turck D, Braegger CP, Colombo C, Declercq D, Morton A, Pancheva R, et al. ESPEN‐ESPGHAN‐ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clinical Nutrition 2016;35(3):557‐77. [PUBMED: 27068495] - PubMed
Van Biervliet 2017
    1. Biervliet S, Declercq D, Somerset S. Clinical effects of probiotics in cystic fibrosis patients: a systematic review. Clinical Nutrition ESPEN 2017;18:37‐43. [PUBMED: 29132736] - PubMed
Vernocchi 2018
    1. Vernocchi P, Chierico F, Russo A, Majo F, Rossitto M, Valerio M, et al. Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype. PloS One 2018;13(12):e0208171. [PUBMED: 30521551] - PMC - PubMed
von Roon 2007
    1. Roon AC, Karamountzos L, Purkayastha S, Reese GE, Darzi AW, Teare JP, et al. Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy. American Journal of Gastroenterology 2007;102(4):803‐13. [PUBMED: 17324124] - PubMed
Werlin 2010
    1. Werlin SL, Benuri‐Silbiger I, Kerem E, Adler SN, Goldin E, Zimmerman J, et al. Evidence of intestinal inflammation in patients with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2010;51(3):304‐8. [PUBMED: 20512061] - PubMed
Yatsunenko 2012
    1. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez‐Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature 2012;486(7402):222‐7. [PUBMED: 22699611] - PMC - PubMed

Publication types

MeSH terms

Substances