AUTHOR=Zhang Tan , Zhang Sina , Jin Chen , Lin Zixia , Deng Tuo , Xie Xiaozai , Deng Liming , Li Xueyan , Ma Jun , Ding Xiwei , Liu Yaming , Shan Yunfeng , Yu Zhengping , Wang Yi , Chen Gang , Li Jialiang 

TITLE=A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients With Cholangiocarcinoma

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.751795

DOI=10.3389/fcimb.2021.751795

ISSN=2235-2988

ABSTRACT=<p>Cholangiocarcinoma (CCA) is a malignant hepatic tumor with a poor prognosis, which needs early diagnosis urgently. The gut microbiota has been shown to play a crucial role in the progression of liver cancer. Here, we explored a gut microbiota model covering genera <italic>Burkholderia-Caballeronia-Paraburkholderia</italic>, <italic>Faecalibacterium</italic>, and <italic>Ruminococcus_1</italic> (B-F-R) for CCA early diagnosis. A case-control study was conducted to enroll 53 CCA patients, 47 cholelithiasis patients, and 40 healthy controls. The feces samples and clinical information of participants were collected in the same period. The gut microbiota and its diversity of individuals were accessed with 16S rDNA sequencing, and the gut microbiota profile was evaluated according to microbiota diversity. Finally, four enriched genera in the CCA group (genera <italic>Bacteroides</italic>, <italic>Muribaculaceae_unclassified</italic>, <italic>Muribaculum</italic>, and <italic>Alistipes</italic>) and eight enriched genera in the cholelithiasis group (genera <italic>Bifidobacterium</italic>, <italic>Streptococcus</italic>, <italic>Agathobacter</italic>, <italic>Ruminococcus_gnavus_group</italic>, <italic>Faecalibacterium</italic>, <italic>Subdoligranulum</italic>, <italic>Collinsella</italic>, <italic>Escherichia-Shigella</italic>) constitute an overall different microbial community composition (P = 0.001). The B-F-R genera model with better diagnostic value than carbohydrate antigen 19-9 (CA19-9) was identified by random forest and Statistical Analysis of Metagenomic Profiles (STAMP) to distinguish CCA patients from healthy controls [area under the curve (AUC) = 0.973, 95% CI = 0.932–1.0]. Moreover, the correlative analysis found that genera <italic>Burkholderia-Caballeronia-Paraburkholderia</italic> were positively correlated with body mass index (BMI). The significantly different microbiomes between cholelithiasis and CCA were found <italic>via</italic> principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe), and Venn diagram and LEfSe were utilized to identify four genera by comparing microbial compositions among patients with malignant obstructive jaundice (MOJ-Y) or not (MOJ-N). In brief, our findings suggest that gut microbiota vary from benign and malignant hepatobiliary diseases to healthy people and provide evidence supporting gut microbiota to be a non-invasive biomarker for the early diagnosis of CCA.</p>