LGG Supplement May Ease CF By Changing Gut Microbiome

Fewer flares, better lung health in children given probiotic daily for 1 year

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Children with cystic fibrosis (CF) whose intestinal microbe populations — or gut microbiome — were dominated by Bifidobacteria had fewer hospitalizations and pulmonary exacerbations, needed fewer antibiotics, and showed lower inflammation in the gut than children with a gut microbiota favoring Bacteroides, a study reported.

A dominance of Bifidobacteria in the children’s gut microbiota also was more likely to be associated with taking Lactobacillus rhamnosus GG (LGG) as a probiotic supplement.

The study, “Gut Bifidobacteria enrichment following oral Lactobacillus-supplementation is associated with clinical improvements in children with cystic fibrosis,” was published in the journal BMC Pulmonary Medicine.

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The gut microbiome consists of bacteria, fungi, and other microbes. It plays a key role in immunity, providing energy, and protecting against the overgrowth of disease-causing pathogens.

Studies have shown that changes in the makeup of the gut microbiome, known as dysbiosis, may contribute to the development of allergies and asthma. Although dysbiosis was found to occur in the gut microbiota of CF patients, a link between the gut microbiota, lung function, or clinical outcomes in this disease has not been demonstrated.

Gut microbiome altered in cystic fibrosis

Use of probiotic supplements is reported to ease intestinal inflammation and lower the number of pulmonary exacerbations, a sudden worsening in respiratory symptoms, in CF patients. But whether it impacts lung function, hospitalizations, or antibiotic use is still unclear.

A Phase 3 clinical trial, Probiotics in Cystic Fibrosis (NCT01956916), failed to show with significance that 12 months of LGG supplementation was effective in reducing exacerbations and hospital stays in children with CF.

Now, a research team at the University of California San Francisco sought to determine if the type of microbiome that develops after taking LGG supplements daily affects outcomes such as lung function, number of exacerbations, intestinal inflammation, and the need for antibiotics.

“LGG may be associated with changes in the gut microbiota in some but not all children, for several reasons including the composition of the pre-treatment gut microbiome, lack of adherence to treatment, diet, or other environmental factors,” the researchers wrote.

Stool samples were analyzed from children with CF enrolled in the Probiotics in Cystic Fibrosis study in Italy, and randomly assigned to a daily oral supplement of either LGG or a placebo.

Before treatment, fecal samples and clinical outcomes were analyzed in 22 patients who were then given LGG and 27 others randomized to a placebo. Their mean age was 8; 25 were boys and 24 were girls. At the study’s end, samples and outcomes were evaluated in 14 children treated daily for one year with LGG and 13 on a placebo.

Pre-treatment, or baseline, samples from most children were dominated by Bifidobacteria (32%) or Bacteroides (18%) bacteria,  genetic analysis showed.

“LGG supplementation was associated with Bifidobacterium-dominated fecal microbiota, whereas placebo-supplemented patients typically exhibited Bacteroides-dominated microbiota,” the team wrote.

Findings in an evaluation of 23 paired baseline and post-study samples also “suggest that daily supplementation with LGG promotes development of distinct gut microbiota, more frequently dominated by Bifidobacteria,” the scientists noted.

LGG supplementation had no effect on fecal alpha diversity, or the relative abundance of microbe species in a sample.

Fecal bacterial beta-diversity, or the similarity between samples, was then examined. Each dominant bacterial genus was associated with a distinct group of bacteria at both baseline and the 12-month visits.

At baseline, no links were found between beta diversity and clinical outcomes. But by the study’s end, several outcomes were associated with gut bacterial beta-diversity.

Further investigations revealed that the rate of pulmonary exacerbations among patients with Bifidobacterium-dominated microbiota was 0.54 less than those dominated with Bacteroides.

Children with Bifidobacterium-dominated microbiota also had better lung function, reflected in a 20% increase in forced expiratory volume in 1 second (FEV1), lower levels of fecal calprotectin — a marker of inflammation in the intestines — and fewer days of prescribed antibiotics.

“These findings suggest that daily supplementation with LGG is associated with Bifidobacteria-dominated fecal microbiota in some, but not all, CF children and that Bifidobacteria-dominated microbiota are associated with improved clinical outcomes,” the scientists wrote.

“They may also offer an explanation for the varied response across CF patient populations to probiotic supplementation and provide early evidence that gut microbiome manipulation is associated with improvements in airway disease status in CF patients,” they added.

According to the researchers, larger clinical trials are needed to confirm these findings.

The randomized and controlled trial in Italy was “the first … that treated patients daily with LGG for an extended time period of 1 year,” the team noted. But “sample size was limited at 12 months, which may have limited our ability to detect significant findings.”