PMID- 36563106 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230214 IS - 1949-0984 (Electronic) IS - 1949-0976 (Print) IS - 1949-0976 (Linking) VI - 15 IP - 1 DP - 2023 Jan-Dec TI - Intratumor microbiome features reveal antitumor potentials of intrahepatic cholangiocarcinoma. PG - 2156255 LID - 10.1080/19490976.2022.2156255 [doi] LID - 2156255 AB - Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with a high prevalence in China. This study aimed to characterize the ICC tissues' bacterial metagenomics signature and explore its antitumor potential for cancer. In this study, 16S rRNA sequencing was carried out on 99 tissues to characterize the features of intratumoral microbiota, followed by single-cell RNA sequencing (scRNA-seq) and multilevel validation. The presence of microbial DNA in tissues was determined using staining, fluorescence in situ hybridization (FISH), and transmission electron microscopy (TEM). A Gram-positive aerobic bacterium, identified as Staphylococcus capitis, was cultured from fresh tissues. Meanwhile, scRNA-seq showed that intratumoral bacteria could be present in multiple cell types. Using 16S rRNA sequencing, we identified a total of 2,320,287 high-quality reads corresponding to 4,594 OTU (operational taxonomic units) sequences. The most abundant bacterial orders include Burkholderiales, Pseudomonadales, Xanthomonadales, Bacillales and Clostridiales. Alpha and Beta diversity analysis revealed specific features in different tissues. In addition, the content of Paraburkholderia fungorum was significantly higher in the paracancerous tissues and negatively correlated with CA199 (Carbohydrate antigen199) levels. The results of in vitro and in vivo experiments suggest that P. fungorum possesses an antitumor activity against tumors. Metabolomics and transcriptomics showed that P. fungorum could inhibit tumor growth through alanine, aspartate and glutamate metabolism. We determined the characteristic profile of the intratumoral microbiota and the antitumor effect of P. fungorum in ICC. FAU - Chai, Xiaoqiang AU - Chai X AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Wang, Jie AU - Wang J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Li, Huanping AU - Li H AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Gao, Chao AU - Gao C AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Li, Shuangqi AU - Li S AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Wei, Chuanyuan AU - Wei C AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Huang, Jianhang AU - Huang J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Tian, Yingming AU - Tian Y AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Yuan, Jian AU - Yuan J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Lu, Jiacheng AU - Lu J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Gao, Dongmei AU - Gao D AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Zheng, Yimin AU - Zheng Y AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Huang, Cheng AU - Huang C AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Zhou, Jian AU - Zhou J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Shi, Guoming AU - Shi G AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Ke, Aiwu AU - Ke A AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Liu, Feng AU - Liu F AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Fan, Jia AU - Fan J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. FAU - Cai, Jiabin AU - Cai J AD - Institutes of Biomedical Sciences, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Gut Microbes JT - Gut microbes JID - 101495343 RN - 0 (RNA, Ribosomal, 16S) SB - IM MH - Humans MH - RNA, Ribosomal, 16S/genetics MH - In Situ Hybridization, Fluorescence MH - *Gastrointestinal Microbiome MH - *Microbiota/genetics MH - Bacteria/genetics MH - *Cholangiocarcinoma/genetics/pathology MH - Bile Ducts, Intrahepatic/pathology MH - *Bile Duct Neoplasms/genetics/pathology PMC - PMC9794006 OTO - NOTNLM OT - ICC OT - P. fungorum OT - amino acid metabolism OT - bacteria OT - metabolomics COIS- The authors declare no conflicts of interest that pertain to this work. EDAT- 2022/12/24 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/12/23 CRDT- 2022/12/23 13:22 PHST- 2022/12/23 13:22 [entrez] PHST- 2022/12/24 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/12/23 00:00 [pmc-release] AID - 2156255 [pii] AID - 10.1080/19490976.2022.2156255 [doi] PST - ppublish SO - Gut Microbes. 2023 Jan-Dec;15(1):2156255. doi: 10.1080/19490976.2022.2156255.