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. 2022 May 15;14(5):2962-2971.
eCollection 2022.

Characteristics of bile microbiota in cholelithiasis, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and pancreatic cancer

Zhengqi Li  1 , Jiangtao Chu  1 , Feixiong Su  2 , Xuan Ding  3 , Yueming Zhang  1 , Lizhou Dou  1 , Yong Liu  1 , Yan Ke  1 , Xudong Liu  1 , Yumeng Liu  1 , Guiqi Wang  1 , Linheng Wang  3 , Shun He  1
Affiliations

Characteristics of bile microbiota in cholelithiasis, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and pancreatic cancer

Zhengqi Li et al. Am J Transl Res. .

Abstract

Significant proof suggests an essential role played by the bile microbiota in biliary diseases. This study retrospectively analyzed the differences in biliary microbes among patients with perihilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA), pancreatic cancer (PC), and cholelithiasis (CH). Bile samples were obtained from 53 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), and the bile microbiota was analyzed through 16S rRNA gene analysis and next-generation sequencing. Based on the results of linear discriminant analysis effect size (LEfSe), the top three biomarkers for pCCA at the genus level were Pseudomonas, Sphingomonas, and Halomonas; for dCCA were Streptococcus, Prevotella, and Halomonas; and for PC were Pseudomonas, Chloroplast, and Acinetobacter. The top five genera in the pCCA, dCCA, and PC groups showed predictive values with areas under the receiver operating characteristic curves of 91.56%, 95.56%, and 96.59%, respectively. The PICRUSt2 analysis outcomes displayed the diversities of fifteen pathways between the CH and pCCA groups, 22 pathways between the CH and dCCA groups, and eighteen pathways between the CH and PC groups. As this pilot study identified specific microbial bile markers for patients with CH, pCCA, dCCA, and PC, the clinical implications are vast. Further study focusing on distinct bacterial populations in bile will help differentiate biliary diseases.

Keywords: Bile microbiota; cholelithiasis; distal cholangiocarcinoma; pancreatic cancer; perihilar cholangiocarcinoma.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
The relative abundance of microbiota in all groups. A. The abundances of phyla in the CH, pCCA, dCCA, and PC groups. B. The abundances of genera in the CH, pCCA, dCCA, and PC groups. C. The α diversity indices of the CH, pCCA, dCCA, and PC groups. D. The β diversity indices of the CH, pCCA, dCCA, and PC groups.
Figure 2
Figure 2
Linear discriminant analysis effect size (LEfSe) analysis of the abundance patterns of bacterial taxa of bile samples. The LEfSe analysis of the (A) CH and pCCA groups, (B) CH and dCCA groups, and (C) CH and PC groups.
Figure 3
Figure 3
Random forest model and ROC results of CH and pCCA groups. A. The random forest model outcomes of 30 genera of CH and pCCA groups. B. ROC analysis of CH and pCCA groups tested top 3-30 genera.
Figure 4
Figure 4
Random forest model and ROC results of CH and dCCA groups. A. Thirty genera of CH and dCCA groups tested for the random forest model outcomes. B. ROC analysis of CH and dCCA groups tested for the top 3-30 genera.
Figure 5
Figure 5
Random forest model and ROC results of CH and PC groups. A. Thirty genera of CH and PC groups tested for the random forest model outcomes. B. ROC analysis of CH and PC groups tested for the top 3-30 genera.
Figure 6
Figure 6
Forecast of functional abilities of CH and pCCA groups. KEGG pathway analysis and the related abundance of genes.
Figure 7
Figure 7
Forecast of functional abilities of CH and dCCA groups. KEGG pathway analysis and the related abundance of genes.
Figure 8
Figure 8
Forecast of functional abilities of CH and PC groups. KEGG pathway analysis and the related abundance of genes.
See this image and copyright information in PMC

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