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Altered microbiome may lead to liver disease in patients with cystic fibrosis

Intestinal lesions were prevalent in adolescents and young adults with cystic fibrosis and cirrhosis and associated with altered fecal microbiome and slower small bowel transit time, according to recently published data.

“While some intestinal symptoms are common in all cystic fibrosis patients, we found there are some who have disturbances in intestinal function with changes in the gut microbiome that may contribute to liver disease,” Michael Narkewicz, MD, professor of pediatrics at University of Colorado School of Medicine and Children’s Hospital Colorado, said in a press release. “We hope this finding will point toward a better understanding of why only 5% to 7% of cystic fibrosis patients develop severe liver disease and will suggest potential therapies to help those patients.”

Michael Narkewicz

Narkewicz and colleagues enrolled 11 patients with cystic fibrosis and cirrhosis and 19 with cystic fibrosis without liver disease aged 7 to 35 years to undergo a series of tests, including small bowel capsule endoscopy, intestinal permeability testing by urinary lactulose, mannitol excretion ratio, fecal calprotectin determination and fecal microbiome characterization. The purpose of the study was to determine the frequency of intestinal lesions and inflammation, alterations in intestinal permeability and characterization of the fecal microbiome in patients with cystic fibrosis with and without cirrhosis as an initial investigation of the potential role of the gut–liver axis in cystic fibrosis liver disease, according to the research.

Patients with cystic fibrosis and cirrhosis had higher gamma-glutamyltransferase compared with patients with cystic fibrosis without liver disease (59 ± 51 U/L vs. 17 ± 4 U/L), as well as lower platelet count (187 ± 126 vs. 283 ± 60) and lower weight z scores (–0.86 ± 1 vs. 0.3 ± 0.9). The patients with cystic fibrosis and cirrhosis had harsher intestinal mucosal lesions on capsule endoscopy (P = .01). Small bowel transit time took longer in patients with cystic fibrosis and cirrhosis compared with patients with cystic fibrosis without liver disease (195 ± 42 minutes vs. 167 ± 68 minutes; P < .001).

Bacteroides were lower in patients with cystic fibrosis and cirrhosis, and they were associated with a lower capsule endoscopy score, according to the research, whereas Clostridium was prevalent in these patients and associated with a higher capsule endoscopy score.

Liver disease was associated with genus-level difference in microbiome. Capsule endoscopy score, the number of red spots, recent hospital admittance for pulmonary exacerbation, previous meconium ileus surgery and a history of varices were associated with differences in fecal microbiome at the genus and phylum levels, according to the research.

“This study provides the first evidence of a link between alterations in the [cystic fibrosis] intestine, fecal microbiome and development of advanced [cystic fibrosis] liver disease,” the researchers concluded. “The evidence supporting the gut–liver axis model in related liver diseases is gaining merit; our study suggests that [cystic fibrosis] is another potential disorder in which interactions between disturbances in intestinal integrity and hepatic inflammatory and fibrogenesis pathways may be active.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.