Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas

被引：48

作者：

Lo, Chia-Hui ^{[1
]}

Wu, Deng-Chyang ^{[2
,3
,4
]}

Jao, Shu-Wen ^{[5
]}

Wu, Chang-Chieh ^{[5
]}

Lin, Chung-Yen ^{[6
]}

Chuang, Chia-Hsien ^{[6
]}

Lin, Ya-Bo ^{[6
]}

Chen, Chien-Hsiun ^{[1
]}

Chen, Ying-Ting ^{[1
]}

Chen, Jiann-Hwa ^{[7
]}

Hsiao, Koung-Hung ^{[8
]}

Chen, Ying-Ju ^{[1
]}

Chen, Yuan-Tsong ^{[1
]}

Wang, Jaw-Yuan ^{[9
,10
,11
]}

Li, Ling-Hui ^{[1
]}

机构：

[1] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[2] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung, Taiwan

[3] Kaohsiung Med Univ, Coll Med, Sch Med, Kaohsiung, Taiwan

[4] Kaohsiung Med Univ, Regenerat Med & Cell Therapy Res Ctr, Kaohsiung, Taiwan

[5] Triserv Gen Hosp, Div Colon & Rectal Surg, Taipei, Taiwan

[6] Acad Sinica, Inst Informat Sci, Taipei, Taiwan

[7] Tzu Chi Gen Hosp, Taipei Branch, Scool Med, Taipei, Taiwan

[8] Tzu Chi Gen Hosp, Dept Colorectal Surg, Taipei Branch, Taipei, Taiwan

[9] Kaohsiung Med Univ, Dept Surg, Div Colorectal Surg, Kaohsiung Med Univ Hosp, Kaohsiung, Miyagi, Taiwan

[10] Kaohsiung Med Univ, Coll Med, Grad Inst Clin Med, Kaohsiung, Taiwan

[11] Minist Hlth & Welf, Pingtung Hosp, Pingtung, Taiwan

来源：

JOURNAL OF BIOMEDICAL SCIENCE | 2022年 / 29卷 / 01期

关键词：

Colorectal cancer; Microbiome; 16S rRNA sequencing; Prevotella intermedia; Fusobacterium nucleatum; Malignant transformation; NATURAL-HISTORY; MICROBIOTA; COLON; BACTERIAL; MUCOSA; CELLS;

D O I：

10.1186/s12929-022-00869-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. Methods Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. Results Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. Conclusion This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

引用

页数：18

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