Gut multi-kingdom and functional microbial signatures represent a promising noninvasive tool that may aid the screening and early identification of cholangiocarcinoma in high-risk populations, complementing existing diagnostic approaches.
Metagenomic sequencing of 700 fecal samples from three regions in China was used to characterize multi-kingdom gut microbiota and function in cholangiocarcinoma (CCA).
CCA patients showed extensive alterations in the gut microbiome across multiple kingdoms and functional layers.
A 21-marker multi-kingdom and functional panel gave the best diagnostic model for CCA, with an average AUC of 91% across three validation cohorts.
The model distinguished CCA from HCC with high specificity.
Benchmarking against clinical guidelines supported a complementary role as a noninvasive screening aid.
The model detected nearly all CCA cases that were negative for CA19-9.
The authors conclude this is the first comprehensive characterization of multi-kingdom gut microbiome and functional markers in CCA.
This study looked at the microbes living in the gut, including bacteria, fungi, archaea, and viruses, in people with cholangiocarcinoma (bile duct cancer). Researchers sequenced stool samples from 700 people in China: 289 with cholangiocarcinoma, 312 healthy people, and 99 with liver cancer (hepatocellular carcinoma). They found large differences in the gut microbes of cholangiocarcinoma patients, spanning hundreds of species across all four groups of microbes, as well as differences in microbial genes, pathways, and enzymes. Using machine learning, the team built a test based on 21 microbial markers. In three independent validation groups it identified cholangiocarcinoma with an average AUC of 91% (a measure of accuracy where higher is better), and it did better than tests using bacteria alone. It could also tell bile duct cancer apart from liver cancer, and it detected 97.6% of cancers that were negative on the standard blood marker CA19-9. This research suggests that stool-based microbial profiles might one day help screen for bile duct cancer in high-risk people without invasive procedures. However, the test's pooled specificity was about 78.5%, so false positives would occur. The authors describe it as a complement to existing diagnostic methods, and it would need further testing before any clinical use.
Rao B, Liu S, Cui G, Jiang J, Li N, Hu J, et al.. (2026). Multikingdom and functional gut microbiota markers for cholangiocarcinoma.. Genome medicine. https://doi.org/10.1186/s13073-026-01757-0