Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 7;25(1):506.
doi: 10.1186/s12876-025-04096-3.

Intestinal microbiota in adults with cholangiocarcinoma identifies the dysregulated Blautia species and bile acid metabolic pathways

Tianyu De  1 , Tian Ma  1 , Wei Wang  1 , Xusheng An  2 , Di Liu  1 , Hongkun Yin  3 , Qi Wang  1 , Ting Zhao  2 , Hao Wang  4
Affiliations

Intestinal microbiota in adults with cholangiocarcinoma identifies the dysregulated Blautia species and bile acid metabolic pathways

Tianyu De et al. BMC Gastroenterol. .

Abstract

Background: Cholangiocarcinoma (CCA) represents a significant global health concern. The gut and bile microbiota, which can influence the gut-liver axis and disease progression, have not been thoroughly characterized in CCA patients.

Methods: We selected two clinical centers at our hospital and collected stool samples from CCA patients and healthy controls (HC). These samples underwent whole-genome metagenomic shotgun sequencing, followed by analysis using both marker gene-based and assembly-based methods. Additionally, KEGG pathway enrichment was performed using the cholangiocarcinoma (CHOL) RNA-seq samples.

Results: Our results revealed distinct dysbiosis of the gut microbiota in our regional CCA patients. The results revealed greater heterogeneity in the gut microbiome of CCA patients compared to HC samples. We found Blautia species to be significantly less abundant in CCA samples, and can distinguish CCA patients from HC. Blautia can also play a role in influencing the modification of secondary bile acids. Additionally, down-regulation of arachidonic acid and linoleic acid metabolism was observed in the tumor tissues of CHOL patients. In summary, the results revealed significant heterogeneity difference in the gut microbiome of CCA patients compared to HC samples, and detected the specifically decreased Blautia species in CCA patients, suggesting that Blautia may influence bile acid metabolic pathways. Further investigation is warranted to explore Blautia as a potential biomarker for CCA.

Keywords: Blautia; Bacterial flora; Cholangiocarcinoma; Microbiomarkers.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Medical Research Ethics Review Committee of Ningxia Medical University General Hospital (KYLL-2024-1316). All procedures of this study were performed following the principles outlined in the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Diversity analysis between CCA and HC groups. A-C Box plot showing the α-diversity results between CCA and HC groups using three indices. D-F Scatter plots showing the β-diversity between CCA and HC groups at three classification levels by PCoA and NMDS analysis
Fig. 2
Fig. 2
Bar plot showing the most dysregulated genus (A) and species (B) between CCA and HC groups
Fig. 3
Fig. 3
The identification of enriched pathways and enzymes in CCA and HC groups. A Bar plot showing the enriched KEGG pathways in CCA and HC groups. The axis represented the enriched fold change compared with each other. B Bar plot showing the relative contribution (percentage) of the top species from three functional analysis results. C Heatmap presentation showing the normalized functional contribution score of top species from three functional analysis results. D PCoA result presentation for the CCA and control samples based on the KO level by random forest analysis. E ROC curve presentation for the diagnostic model based on KO levels
Fig. 4
Fig. 4
Functional enrichment analysis for the DEGs between CHOL tumor and normal samples. A Bar plot showing the enriched GO pathways for down DEGs in CHOL samples. B Bar plot showing the enriched GO pathways for up DEGs in CHOL samples. C Bubble plot showing the enriched KEGG pathways for down DEGs in CHOL samples. D Bubble plot showing the enriched KEGG pathways for up DEGs in CHOL samples
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE, Teh BT, Wongkham S. Gores GJ: cholangiocarcinoma. Nat Reviews Disease Primers. 2021;7(1):65. - PMC - PubMed
    1. Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Reviews Gastroenterol Hepatol. 2011;8(9):512–22. - PMC - PubMed
    1. Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, Cardinale V, Carpino G, Andersen JB, Braconi C, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Reviews Gastroenterol Hepatol. 2020;17(9):557–88. - PMC - PubMed
    1. Park EM, Chelvanambi M, Bhutiani N, Kroemer G, Zitvogel L, Wargo JA. Targeting the gut and tumor microbiota in cancer. Nat Med. 2022;28(4):690–703. - PubMed
    1. Pabst O, Hornef MW, Schaap FG, Cerovic V, Clavel T, Bruns T. Gut-liver axis: barriers and functional circuits. Nat Reviews Gastroenterol Hepatol. 2023;20(7):447–61. - PubMed

Substances

Grants and funding

LinkOut - more resources