About 30% of patients with cystic fibrosis report liver abnormalities and 10% of these patients go on to experience severe liver disease. Traditionally, cystic fibrosis-related liver disease was thought to be caused primarily by defective bile secretion due to the dysfunctional CFTR protein, which limited treatment options. Yale’s recent study led by Romina Fiorotto, PhD, and Mario Strazzabosco, MD, PhD, has identified a connection between the gut microbiome and the development of liver disease in cystic fibrosis patients.
Roughly 100 trillion microorganisms form the human gut microbiome, aiding in digestion, immunity, metabolism, and other bodily processes. Researchers have previously found that disturbances to this microbiome contribute to the development of many diseases. This study analyzed the gut and liver in preclinical cystic fibrosis models. Significantly, these models showed harmful gut microbiota, increased intestinal permeability, and inflammation. The researchers found that these intestinal changes were pivotal for developing cystic fibrosis-related liver disease. Notably, the study demonstrated that restoring intestinal CFTR function or using antibiotics to correct imbalances in microorganisms can help reduce liver inflammation.
These findings shed new light on the crucial role of the gut microbiota in the promotion of cystic fibrosis-related liver disease and open new avenues for preventing or treating this disease. In addition, this study represents an important proof of concept for the role of intestinal microbiome imbalances in diseases of the biliary tree.
To learn more, read the paper, “Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice.”
Bertolini A, Nguyen M, Zehra SA, Taleb SA, Bauer-Pisani T, Palm N, Strazzabosco M, Fiorotto R. Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice. J Hepatol. 2024 Mar 28:S0168-8278(24)00225-3. doi: 10.1016/j.jhep.2024.03.041. Epub ahead of print. PMID: 38554847.