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. 2022 May 27;22(1):147.
doi: 10.1186/s12866-022-02557-3.

Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis

Mari Kirishima #  1 , Seiya Yokoyama #  1 , Kei Matsuo  1 , Taiji Hamada  1 , Michiko Shimokawa  1 , Toshiaki Akahane  1 , Tomoyuki Sugimoto  2 , Hirohito Tsurumaru  3 , Matsujiro Ishibashi  3 , Yuko Mataki  4 , Takao Ootsuka  4 , Mitsuharu Nomoto  1 , Chihiro Hayashi  5 , Akihiko Horiguchi  5 , Michiyo Higashi  1 , Akihide Tanimoto  6
Affiliations

Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis

Mari Kirishima et al. BMC Microbiol. .

Abstract

Background: The microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports characterizing the bile microbiota are rare. This study aims to investigate the microbiota composition in patients with pancreaticobiliary cancers and benign diseases by 16S rRNA gene amplicon sequencing and to evaluate its potential value as a biomarker for the cancer of the bile duct, pancreas, and gallbladder.

Results: We enrolled patients who were diagnosed with cancer, cystic lesions, and inflammation of the pancreaticobiliary tract. The study cohort comprised 244 patients. We extracted microbiome-derived DNA from the bile juice in surgically resected gallbladders. The microbiome composition was not significantly different according to lesion position and cancer type in terms of alpha and beta diversity. We found a significant difference in the relative abundance of Campylobacter, Citrobacter, Leptotrichia, Enterobacter, Hungatella, Mycolicibacterium, Phyllobacterium and Sphingomonas between patients without and with lymph node metastasis.

Conclusions: There was a significant association between the relative abundance of certain microbes and overall survival prognosis. These microbes showed association with good prognosis in cholangiocarcinoma, but with poor prognosis in pancreatic adenocarcinoma, and vice versa. Our findings suggest that pancreaticobiliary tract cancer patients have an altered microbiome composition, which might be a biomarker for distinguishing malignancy.

Keywords: Alpha diversity; Beta diversity; Bile; Biomarker; Cancer; Gallbladder; Microbiota; Overall survival; Pancreaticobiliary tract; Prognosis.

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Conflict of interest statement

We declare no competing interests.

Figures

Fig. 1
Fig. 1
The alpha analysis of microbiota in Bile juice collected from gallbladder. Microbiota alpha diversity in bile collected from resected gallbladders in pancreaticobiliary tract and gallbladder cancers. Microbiome composition analysis at the genus level (A). Alpha diversity of Shannon, Chao1, and Pielou evenness indices as well as Faith PD according to the location of the lesion (B) or type of lesion (C). PDAC, pancreatic ductal adenocarcinoma; BDAC, cholangiocarcinoma; GDAC, gallbladder cancer; P-cystic, pancreas cystic lesion; faith_pd, Faith PD; pielou_e, Pielou evenness index
Fig. 2
Fig. 2
The beta diversity analysis of microbiota in Bile juice collected from gallbladder. Microbiota beta diversity in bile collected from resected gallbladders in pancreaticobiliary tract and gallbladder cancers. The beta diversity analysis at the genus level of 16S rRNA gene amplicon sequencing pattern by NMDS (A) and PCoA (B) among the lesion locations or lesion type. The type of cancer includes pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma (BDAC) and gallbladder cancer (GDAC). The type of cystic is a pancreas cystic lesion. Dim, dimension; N, trends in these variances with the N-score of TNM classification; M, trends in these variances with the M-score of TNM classification; NMDS, Non-metric multidimensional scaling; PCoA, principal coordinate analysis
Fig. 3
Fig. 3
Association between cluster analysis and its prognosis in bile duct lesion and pancreas lesion. Cluster analysis of the relative abundance of microbiota in bile juice at gallbladder. A Tree generated by cluster analysis of total sample collected from including bule duct lesion, pancreas lesion and other lesion for the relative abundance (permyriad of total sequences). Cox proportional hazard regression analysis on a comparison between Cluster 1 and Cluster2 (B) in bile duct lesion and (C) in pancreas lesion. Black line: Cluster 1, red line: Cluster 2
Fig. 4
Fig. 4
Comparison relative abundance of microbiota between Cluster 1 and Cluster 2. Comparison relative abundance of microbiota between the Cluster 1 and the Cluster 2 on clustering analysis. The color of plot means location of lesion. The red plot, bile duct lesion; the blue plot, gallbladder lesion; the green plot, pancreas lesion; the black plot, other. The plot shape means type of lesion. ■, cancer; ▲, cystic lesion; ●, benign; ×, Other
See this image and copyright information in PMC

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