Bacteria from the gut appear to contribute to liver damage in primary biliary cholangitis (PBC) by moving beyond the intestine and triggering inflammation in the liver, a new study published in Gut Pathogens suggests.
Researchers found that transplanting fecal microbiota from five patients with PBC to five mice caused liver injury and inflammation around the bile ducts — changes also seen in PBC. Mice that received fecal microbiota from healthy donors did not show the same pattern of liver injury.
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In addition to the liver and bile duct damage, the mice with PBC microbiome transplants saw larger changes to the composition of their gut bacteria: They had fewer beneficial gut bacteria, and more potentially harmful bacteria. They also showed damage to the intestinal barrier, which normally helps prevent bacteria from passing beyond the gut.
Another important finding was the presence of the bacterium Klebsiella pneumoniae, which was found both in mice that received PBC patient microbiota and in liver samples from 11 of 14 patients with PBC.
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In an analysis of liver samples from nine patients with PBC, researchers found that higher numbers of bacteria in the liver was associated with higher levels of blood markers of liver injury and impaired bile flow. Patients who did not respond to treatment with ursodeoxycholic acid (UDCA, the standard first-line treatment for PBC) had more K. pneumoniae in their livers than those who responded.
In a separate experiment, the researchers inserted K. pneumoniae into the mice’s gastrointestinal system via feeding tubes. K. pneumoniae was later found in the liver tissue of these mice, confirming that the bacterium can move through the protective barrier of the intestines and to the liver, where it causes liver injury.
To investigate whether an antibiotic could limit this damage, the researchers tested metronidazole in mice that received microbiota from patients with PBC. The treatment lowered alanine aminotransferase (ALT) levels (a marker of liver damage) and reduced liver inflammation. However, it also decreased some beneficial gut bacteria and increased some potentially harmful ones. The authors emphasized that these findings do not support using metronidazole to treat PBC in patients.
The researchers noted that “clinical human data remain only associative,” meaning they cannot tell whether the bacteria contribute to liver damage in patients or whether existing liver damage makes it easier for the bacteria to reach and colonize the liver. Therefore, finding the bacteria in patients’ livers does not establish that eliminating them would improve PBC.
