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Stalled Microbiomes: Cystic Fibrosis Disrupts Early Gut Development In Infants

Findings from a new Dartmouth-led study, published in the journal mBio, highlight key differences in the gut microbiome (communities of bacteria) of infants with cystic fibrosis (CF) compared to that of healthy infants, and how these alterations may adversely affect their health. CF is a multi-organ genetic disease that causes sticky mucus to build up in the lungs and digestive system, as well as heightened inflammation in the gut and at other body sites.

"It's been known that in healthy infants, the intestinal microbiome is very dynamic and changes over time as a consequence of how they're delivered at birth, whether they're breastfed or not, and when they transition to solid food, among other factors. Then at three to five years of age, these changes stabilize into an adult-like microbiome. This process is key to healthy development," explains lead author Benjamin Ross, PhD, an assistant professor of microbiology and immunology at Dartmouth's Geisel School of Medicine.

"We didn't really know how that process played out in infants with CF, so we set out to study how the gut microbiome of infants with the disease matured and if that maturation process was different compared to healthy kids," says Ross, whose collaborators at Geisel and Dartmouth Health included George O'Toole, PhD, Juliette Madan, MD, MS, and Julie Sanville, DO.

For their study, the investigators recruited a cohort of 40 infants with CF from the Northern New England area who were cared for and followed at Dartmouth Hitchcock Medical Center between 2009 and 2019. The team used DNA sequencing techniques to analyze the bacterial composition of stool samples of the infants from birth to three years.

They then compared the types of bacteria found in the microbiomes of the local CF infant cohort with those found in healthy infants -- which were taken from large, publicly available data sets across the U.S. And in Northern Europe.

"Our major conclusion was that in CF the microbiome really doesn't change very much, so it's essentially stunted or delayed in its maturation compared to healthy kids, and this failure to mature may contribute to poor health," says Ross. "For example, we found a depletion of health-associated bacteria in the CF kids, including Faecalibacterium Prausnitzii, which is a bacterium that specializes in using dietary fiber as an energy source and is known to stimulate anti-inflammatory responses."

Ross and his colleagues are planning follow-up studies using mouse models to better understand why these alterations in the gut microbiome occur in CF and what the consequences are on health.

"We hope this work can include testing and developing interventions, such as probiotics or dietary changes, that may help mitigate the effect of the disease on the microbiome or supplement it with aspects that will help rescue microbiome deficiencies," he says.

Everything To Know About Cystic Fibrosis And What Causes It

Breathing disorders are common in the U.S. With conditions like COPD affecting some 7% of the population and asthma affecting another 10%. Digestive conditions like GERD, acid reflux, Celiac disease and IBS negatively impact countless millions more.

The genetic disorder cystic fibrosis is unique because it can cause both breathing and digestive problems. Some 40,000 people in the U.S. currently have it, "though this is likely an underestimate as many patients may have mild forms of the condition and remain undiagnosed," says Dr. Ashwin Basavaraj, system chief of pulmonary medicine at NYC Health + Hospitals.

Here's what cystic fibrosis is, what causes it and how it's usually treated once it has been diagnosed.

What is cystic fibrosis (CF) disease?

Cystic fibrosis (CF) is a progressive genetic disease that adversely affects a person's lungs, pancreas and other vital organs, says Dr. Michael Boyle, president and CEO of the Cystic Fibrosis Foundation in Bethesda, Maryland. The disease impacts the lungs by clogging airways with sticky, thick mucus, which traps bacteria and other germs and sometimes leads to inflammation, respiratory infections and even respiratory failure.

The buildup of mucus in the pancreas can also prevent the release of digestive enzymes that help the body absorb food, "leading to digestive abnormalities, malnutrition and stunted growth," says Basavaraj.

Other common symptoms of CF include coughing attacks (often with phlegm), shortness of breath, greasy and bulky stools, rectal prolapse and constipation. "People with CF are also more susceptible to sinus and respiratory infections and often require persistent use of antibiotics, leading to concerns over antibiotic resistance," adds Boyle.

CF can also affect the liver, sometimes causing liver disease, as well as impact the reproductive system, sometimes "causing infertility in men," says Basavaraj.

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What causes cystic fibrosis? Is cystic fibrosis genetic?

Cystic fibrosis is caused by mutations in a gene known as the cystic fibrosis transmembrane conductance regulator (CFTR), says Basavaraj. He explains that these mutations eventually cause a protein imbalance and water and salt in the body's cells to surface, "resulting in mucus becoming thick and sticky, and difficulty clearing airways and other organs."

In other words, people with CF are born with the disease, inheriting a copy of this gene from each parent, says Boyle.

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How is cystic fibrosis treated?

While there is no cure for CF, there are multiple treatment options. Basavaraj says such options include bronchodilators to help open airways; mucus-thinning medications to help clear up the sticky substance; high-frequency chest wall oscillation (HFCWO) devices to help clear mucus from the lungs; and pancreatic enzymes to help with digestion and nutrient absorption.

Moreover, "there are currently five FDA-approved CFTR modulator oral therapies on the market that each address the underlying cause of cystic fibrosis," adds Boyle. These were developed to be effective against specific mutations and more modulator therapies are in development.

Despite the many advantages these therapies provide, "approximately 10% of individuals cannot benefit from modulators due to their genetic mutations or ability to tolerate the treatment," says Boyle. Because of this, he says, "many people living with CF are still waiting for their breakthrough, which is why we are urgently pursuing efforts to ensure there are treatments available to them."

This article originally appeared on USA TODAY: What is cystic fibrosis?

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