Changes in the gut microbiome configuration could negatively affect the response to ursodeoxycholic acid (UDCA) treatment in patients with primary biliary cholangitis (PBC), according to a recently published study in Med.
“These findings suggest that baseline microbial composition may predict treatment response and offer novel insights into PBC pathogenesis,” the study concluded.
UDCA represents first-line therapy for patients with PBC. But a significant percentage of patients respond poorly to UDCA, and the lack of other therapeutic alternatives results in an increased risk of severe hepatic insufficiency and death.
The variable response rate towards first-line treatment and the lack of therapeutic alternatives create a need to understand the factors that influence UDCA effectiveness and possible measures to increase treatment response.
Learn more about PBC treatment and care
Some studies have demonstrated gut microbiome abnormalities in patients with PBC; however, several limitations, such as small samples, prevent a full understanding of the relevance of those abnormalities.
What is PBC?
Primary biliary cholangitis (PBC) is a rare, chronic autoimmune disease that primarily affects the liver. In PBC, the body’s immune system mistakenly attacks the small bile ducts within the liver, causing inflammation and gradual destruction of these ducts. Bile, a substance essential for digesting fats and removing toxins, becomes trapped in the liver, leading to liver damage over time.
To determine the role of the gut microbiome in UDCA response, the study used machine learning to analyze the collective genome of microorganisms (metagenomic sequencing) and the metabolites (metabolomic profile) in more than 100 stool samples before and after UDCA treatment.
In light of the findings, researchers divided patients into two groups according to changes in the abundance of Clostridia species. Patients in the low Clostridia group had a lower response to UDCA than patients in the high Clostridia group. The findings correlated with a decrease in the production of certain molecules important for immune regulation.
In recent decades, the role of the gut microbiome in many diseases, including autoimmune conditions and cancer, has become increasingly clear. Furthermore, abundant research suggests the gut microbiome could play a key role in other liver diseases, such as primary sclerosing cholangitis.
“Although attempts have been made to establish prognosis models based on clinical parameters, these approaches offer limited insight into the molecular basis of patient variability in response to UDCA,” the researchers stated.
