Antibiotics, CF Gut Dysfunction May Lead to Unbalanced Gut Microbiota

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Cystic fibrosis (CF) patients show a shift in gut microbiota composition toward more abundant, rarer populations that is significantly associated with antibiotic use, CF disease, and CF-associated changes in gut function and transit, a study shows.

These findings add to previous studies showing that CF patients have reduced gut microbiota diversity and provide potential explanations for such alterations, identifying not only disease-associated mechanisms, but also clinical factors (antibiotics) as the culprits.

Further studies are needed to better understand these associations, namely those reflecting the so-called gut-lung axis, which could help identify new therapeutic approaches, the researchers noted.

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The study, “Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis,” was published in the Journal of Cystic Fibrosis.

The excessive production of mucus seen in people with CF not only affects the lungs, but also their gastrointestinal system. An increasing number of studies have reported gut dysbiosis in CF patients across all ages.

Gut dysbiosis is an imbalance in the populations of friendly microbes naturally present in the gut, also known as gut microbiota. This microbial community helps to maintain a balanced gut function, protect against disease-causing organisms, and influence a person’s metabolism and immune system.

Gut microbiota imbalance in CF patients has been associated with “intestinal inflammation, intestinal lesions, and increased gene [activity] relating to intestinal cancers,” the researchers wrote.

In addition, previous research supports the existence of a gut-lung axis, in which both organs communicate bidirectionally through both microbial and immune interactions, shaping immune responses and interfering with the course of lung diseases.

Now, a team of researchers in the U.K. investigated the potential associations between gut microbiota and gastrointestinal function, transit, and other CF-associated factors in 10 CF patients (ages ranging from 12 to 36) and 10 age- and sex-matched healthy people (used as controls).

Participants’ stool samples were collected and analyzed through a genetic sequencing method to determine the composition and diversity of their gut microbiota. The levels of fecal calprotectin protein, a biomarker of intestinal inflammation, were also assessed.

On the same day of stool collection, patients underwent magnetic resonance imaging (MRI) scans to assess their gut function and transit and completed a three-day food diary relative to the three previous days.

Results showed that CF patients had significantly reduced gut microbiota diversity relative to healthy people, consistent with previous findings. In addition, CF was associated with a shift toward a greater abundance of rarer populations, while common populations were less abundant than in controls.

Differences between groups were found to be driven by a variety of bacterial populations, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. Some of these population changes were previously associated with poor growth and intestinal inflammation.

Both common and rarer populations were significantly more similar within the control group than in the CF group. This may be explained by CF-associated factors such as varied antibiotic use and the broad range of included CF patients with varied lifestyle factors, the team noted.

These data suggest the existence of a perturbed microbial community “harbouring greater instability, less subsequent resilience, and inherent challenges to the colonisation and establishment of [normal populations],” the researchers wrote.

Further analyses showed that changes in common bacterial populations were explained mostly by CF disease, followed by sex and body-mass index — a measure of body fat.

In contrast, the abnormally abundant rarer populations — and consequently the whole microbiota — were associated mainly with antibiotic use and CF disease, followed by gut function and transit and fecal calprotectin levels.

Increased levels of fecal calprotectin were previously associated with increased abundances of particular bacterial populations that were significantly higher in the CF group.

Dietary profiles “were similar between groups and did not contribute to significant variation in the microbiota,” the researchers wrote.

These findings highlight that the common bacterial populations observed in CF patients are largely explained by the presence of CF disease itself, perhaps related to the impaired flow of water and ions and subsequent excessive mucus that characterizes and drives the disease, the team noted.

Antibiotic use and “alterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa [rarer populations],” the researchers wrote.

“Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon,” they added.

Further and larger studies are needed to confirm and clarify these associations, as well as to better understand the gut-lung axis and its contribution to CF.

Also, as the first study to use microbiota gene sequencing with noninvasive MRI to assess underlying gut problems, “we demonstrate the potential for future collaborations between gastroenterology and microbiology … to investigate these relationships between gut function and the microbiome further,” the team concluded.