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Probiotic supplementation in children with cystic fibrosis—a systematic review

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Abstract

Probiotics may benefit in cystic fibrosis (CF) as gut dysbiosis is associated with gastrointestinal symptoms and exacerbation of respiratory symptoms in CF. We conducted a systematic review of randomized controlled trials (RCTs) and non-RCTs of probiotic supplementation in children with CF, using the Cochrane methodology, preferred reporting items for systematic reviews (PRISMA) statement, and meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Primary outcomes were pulmonary exacerbations, duration of hospitalization and antibiotics, and all-cause mortality. Secondary outcomes included gastrointestinal symptoms, markers of gut inflammation, and intestinal microbial balance. A total of nine studies (RCTs, 6, non-RCTs, 3; N = 275) with some methodological weaknesses were included in the review. The pooled estimate showed significant reduction in the rate of pulmonary exacerbation (fixed effects model, two parallel group RCTs and one cross-over trial: relative risk (RR) 0.25, (95 % confidence interval (95 % CI) 0.15,0.41); p < 0.00001; level of evidence: low) and decrease in fecal calprotectin (FCLP) levels (fixed effect model, three RCTs: mean difference (MD) −16.71, 95 % CI −27.30,−6.13); p = 0.002; level of evidence: low) after probiotic supplementation. Probiotic supplementation significantly improved gastrointestinal symptoms (one RCT, one non-RCT) and gut microbial balance (decreased Proteobacteria, increased Firmicutes, and Bacteroides in one RCT, one non-RCT).

Conclusion: Limited low-quality evidence exists on the effects of probiotics in children with CF. Well-designed adequately powered RCTs assessing clinically meaningful outcomes are required to study this important issue.

What is Known:

• Gut dysbiosis is frequent in children with cystic fibrosis due to frequent exposure to pathogens and antibiotics.

• Probiotics decrease gut dysbiosis and improve gut maturity and function.

What is New:

• This comprehensive systematic review shows that current evidence on the safety and efficacy of probiotics in children with cystic fibrosis is limited and of low quality.

• Well-designed and adequately powered trials assessing clinically important outcomes are required considering the health burden of cystic fibrosis and the potential benefits of probiotics.

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Abbreviations

BMI:

Body mass index

CF:

Cystic fibrosis

FCLP:

Fecal calprotectin

FEV:

Forced expiratory volume

GI:

Gastrointestinal

LGG:

Lactobacillus GG

RCT:

Randomized controlled trial

RNO:

Rectal nitric oxide

ORS:

Oral rehydration solution

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Author’s contribution

AA is responsible for literature review, analysis, and writing the first draft. HB is responsible for literature review and analysis. SR is responsible for synthesis and checking the first and the final versions of the manuscript. SP is responsible for concept, supervision, interpretation of results, and checking the first and the final versions of the manuscript.

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Authors and Affiliations

  1. Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, 378 Bagot Road, Subiaco, Perth, WA, 6008, Australia

    Anitha Ananthan, Haribalakrishna Balasubramanian & Sanjay Patole

  2. Department of Neonatal Paediatrics, Princess Margaret Hospital for Children, Perth, WA, Australia

    Shripada Rao

  3. Centre for Neonatal Research and Education, University of Western Australia, Crawley, Australia

    Shripada Rao & Sanjay Patole

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  1. Anitha Ananthan
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  2. Haribalakrishna Balasubramanian
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Ananthan, A., Balasubramanian, H., Rao, S. et al. Probiotic supplementation in children with cystic fibrosis—a systematic review. Eur J Pediatr 175, 1255–1266 (2016). https://doi.org/10.1007/s00431-016-2769-8

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