Use of probiotics in cystic fibrosis

Complementary therapies are gaining popularity among the cystic fibrosis (CF) cohort, with recent estimates suggesting up to 75% of children with CF use these therapies alongside conventional medicine.^1,2 Therefore, it is important for dietitians to keep up-to-date with these types of therapies so as to best guide their patients on the evidence for use. 

Probiotics

One such complementary therapy – probiotics – is being used increasingly by patients with CF. A probiotic is an orally administered live bacterial load thought to beneficially affect the gastrointestinal (GI) microbial balance. The normal balance and composition of bacteria in the GI tract can be disturbed during periods of illness, compromised dietary intake, infection and antibiotic use. These disturbances are thought to affect gut microflora composition by altering the availability of different substrates for bacterial fermentation. As such, probiotics are thought to help redress the balance by adding back live beneficial bacteria. Alterations in the gut microbiota have been associated with inflammatory conditions such as IBS, IBD and allergic respiratory disease.

The benefit of probiotics in CF is yet to be proven but evidence is gathering in the non-CF population that probiotic use may have a role in reducing illness. A number of studies have found that probiotics decrease the symptom severity of acute paediatric gastroenteritis.^3,4 An adult study in 2010 found the probiotic strain, L rhamnosus GG, helped prevent respiratory infections,⁵ however that said, no study in the paediatric population has replicated this finding.⁶

There is also evidence gathering of a role in reducing GI inflammation. One study in IBS patients with an abnormal IL-10/IL12 ratio – (indicative of a pro-inflammatory TH-1 state), used the strain B infantis 35624 daily for eight weeks and found an alleviation in GI symptoms and a normalisation of the ratio of anti-inflammatory to pro-inflammatory cytokines.⁷

Probiotic efficacy has been demonstrated in the treatment of antibiotic and Clostridium difficile-related diarrhoea.^{8, 9} Most probiotics need to be continued to see a long-term benefit as four weeks post-cessation of treatment, they tend to have left the gut.⁸

It is also worth noting that not all probiotics are created equally and purported efficacy of probiotics cannot be applied equally across different strains as the mode of action and worth are often strain-specific.¹⁰

Probiotics in the CF population

Respiratory exacerbations

Chronic infection and inflammation are key clinical consequences of CF. Chronic infection and disease appear early in the CF lung. Despite the lungs being ‘normal’ at birth, the dysfunction of the CF transmembrane regulator gene leads to altered passage of salt and water across cell membranes, eventually causing thickened secretions that go on to obstruct the small airways. Over time, these obstructions cause infection and inflammation. 

While physiotherapy, bronchodilators and steroids aim to open the airways again, antibiotics are frequently needed to restore lung function. A reduction in the incidence of respiratory exacerbations has been shown in people with CF taking the lactobacillus GG strain.^{11, 12, 13} However, reductions in frequency of respiratory exacerbations did not translate into improvements in lung function.^11,12 Another small pilot study in children with CF demonstrated reduced frequency of hospital admissions in those supplemented with probiotics.¹⁴

GI inflammation

The gut microbiota in those with CF is thought to be different than those without CF. Over the past five years, imbalances in the CF gut have been identified in a number of studies showing an increase in pathogenic bacteria and a reduction in beneficial bacteria. A number of pilot studies in paediatric patients with CF have demonstrated a reduction in GI inflammatory markers post one to six-month course of lactobacillus supplementation.^{15, 16} Another study found that following probiotic supplementation, there was a partial restoration of the normal intestinal microbiota.¹⁷

Probiotics in practice with the CF patient

Probiotics have certainly entered the mainstream of healthcare thinking and are more often than not a consideration in those with compromised gut function and increasingly extraintestinal health such as respiratory health. 

Probiotics have a long safety record, with the strains of lactobacilli and bifidobacteria (already normal residents of the human GI tract) being the most studied.^{18, 19} There is the possibility that long-term probiotic use may have the potential for transfer of antibiotic resistance but this risk seems to be low. A large review in immune-compromised adults found no significant adverse effects related to use. However, in patients with severe respiratory disease, it is probably wise to use probiotics with caution until there is more vigorous evidence regarding their safety.⁹ The Food Safety Authority of Ireland has not approved any health claims for probiotics and any terms that imply a probiotic function are not permitted in Ireland.

If you decide to recommend probiotics to particular patients with CF:

• Use a probiotic for which there is evidence. Lactobacilli and bifidobacteria strains have the most evidence for dietitians

• Avoid using probiotics post-transplant or in those who are severely immune-compromised

• Use reputable products which contain adequate numbers of bacteria

• Encourage consistent daily intake for best effect

• Be aware of the financial impact on patients. For example the probiotic Alflorex (strain 35624 B Infantis) is available to CF patients on their long-term illness card in Ireland. Otherwise the monthly cost of probiotics is typically €30 per month or €360 per year 

• Advise patients to finish the probiotics or try another brand if there is no discernible benefits observed after a four-week trial

There is good rationale for trying probiotics in the treatment of those with CF experiencing antibiotic-related diarrhoea and Clostridium diffcile-related diarrhoea

Effects of probiotics in CF have demonstrated numerous benefits on health outcomes, but it is important to be aware that the studies to date are not of a consistently high enough quality to make any far-reaching recommendations. Dietitians should monitor their patients carefully on probiotics and look for improvements in outcome pre and post -supplementation to discern efficacy and justify use. In the CF cohort, the most likely improvements will relate to reduction in symptoms such as abdominal pain, bloating, wind and frequency and consistency of bowel motions. The emerging evidence for use of probiotics in this patient group, while still deserving of further study, is nonetheless promising.

References

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