Microbial Community Heterogeneity Within Colorectal Neoplasia and its Correlation With Colorectal Carcinogenesis

Liu, Weixin; Zhang, Xiang; Xu, Hui; Li, Shengmian; Lau, Harry Cheuk-Hay; Chen, Qiongyun; Zhang, Bin; Zhao, Liuyang; Chen, Huarong; Sung, Joseph J.Y.; Yu, Jun

doi:10.1053/j.gastro.2021.02.020

Cited by 100 publications

(83 citation statements)

References 32 publications

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“…(3) Patients with metastasis or recurrence have more intratumoral F. nucleatum than patients without metastasis or recurrence ( Chen Y. et al, 2020 ; Yu et al, 2017 ). (4) Even in the same tumor tissues, the abundance of F. nucleatum varies at different sampling sites ( Liu W. et al, 2021 ).…”

Section: F Nucleatum and Crc: Clinical Studies In Different Sample Typesmentioning

confidence: 99%

Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Colorectal cancer (CRC) is a common cancer worldwide with complex etiology. Fusobacterium nucleatum (F. nucleatum), an oral symbiotic bacterium, has been linked with CRC in the past decade. A series of gut microbiota studies show that CRC patients carry a high abundance of F. nucleatum in the tumor tissue and fecal, and etiological studies have clarified the role of F. nucleatum as a pro-carcinogenic bacterium in various stages of CRC. In this review, we summarize the biological characteristics of F. nucleatum and the epidemiological associations between F. nucleatum and CRC, and then highlight the mechanisms by which F. nucleatum participates in CRC progression, metastasis, and chemoresistance by affecting cancer cells or regulating the tumor microenvironment (TME). We also discuss the research gap in this field and give our perspective for future studies. These findings will pave the way for manipulating gut F. nucleatum to deal with CRC in the future.

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Section: F Nucleatum and Crc: Clinical Studies In Different Sample Typesmentioning

confidence: 99%

Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…In this study, we found that the abundance of Fusobacterium nucleatum increased in the test group, and this increase is possibly related to terminal ileal NLH. Fusobacterium nucleatum has been reported to be enriched in colorectal cancer tissues and played a crucial role in the occurrence and development of colorectal cancer[ 32 ]. It can adhere to and invade intestinal epithelial cells and activate the β-catenin pathway by releasing FadA adhesin and binding with cadherin E-cadherin, thus promoting inflammation and tumor response[ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Mucosal bacterial dysbiosis in patients with nodular lymphoid hyperplasia in the terminal ileum

Jiang¹,

Lü²,

Zhang³

et al. 2022

WJG

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BACKGROUND Nodular lymphoid hyperplasia (NLH) in the small intestine is a rare benign lesion characterized by multiple small nodules on the intestinal surface. Patients with terminal ileal NLH may experience long-term abdominal pain, diarrhea, and abdominal distension, among other symptoms. Supplementation with probiotics could mitigate these symptoms. NLH is linked to the immune system, and it may result from accumulation of plasma-cell precursors due to a maturational defect during the development of B lymphocytes. The intestinal microbiome plays an essential role in the immune system. Thus, we speculate that the gut flora plays a key role in terminal ileal NLH. AIM To explore the correlation between intestinal flora and terminal ileal NLH. METHODS We collected mucosal biopsy samples that were obtained via colonoscopy from 15 patients with terminal ileal NLH (the test group) and 15 normal subjects (the control group). We subsequently performed 16S-rRNA gene amplicon sequencing of these samples, and the results were evaluated using alpha diversity, beta diversity and microbial composition analyses. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to predict the metabolic pathways and orthologous groups according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS Compared with the control group, the terminal ileal NLH group showed an increased alpha diversity ( P < 0.05). The overall intestinal microbiota in the NLH group was significantly different from that of the control group ( P < 0.05), implying that there was the dysbiosis in the terminal ileal NLH patients. The relative abundance of phylum Bacteroidetes was significantly lower in the NLH group, while that of Patescibacteria and Campilobacterota was significantly higher. The genus Bacteroides was the dominant gut microbiota in both groups, but its abundance was significantly lower in the test group than it was in the control group. Conversely, the relative abundances of Haemophilus, Streptococcus, Pseudomonas, Actinomyces, TM7X, Fusobacterium nucleatum, Parvimonas, Granulicatella, Helicobacter , and the [ Eubacterium ] nodatum group were significantly higher in the test group than they were in the control group. In addition, several altered metabolic pathways, orthologous groups, and modules were found. For example, the Peptidoglycan biosynthesis and Aminoacyl tRNA biosynthesis were both increased in the test group. CONCLUSION Maintaining the microbial balance and supplementing targeted protective bacteria could improve symptoms and potentially reduce the risk of lymphoma transformation in patients with terminal ileal NLH.

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“…The exact nature of how colibactin production may alter transcriptional regulation or abundance of gut microbes is not well understood. However, the relevance of microbial dysbiosis in the etiology of various cancers is well-defined [70][71][72]. Future studies focusing on how colibactin influences multi-kingdom interactions in the gut may elucidate novel pathways by which pks + bacterial colonization deleteriously affects their host.…”

Section: Modulation Of Tumor Microenvironmentmentioning

confidence: 99%

Shining a Light on Colibactin Biology

Dougherty

Jobin

2021

Toxins

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Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of pks+ E. coli in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin’s structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.

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Microbial Community Heterogeneity Within Colorectal Neoplasia and its Correlation With Colorectal Carcinogenesis

Abstract: Author names in bold designate shared co-first authorship.

Cited by 100 publications

References 32 publications

Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality

Fusobacterium nucleatum Acts as a Pro-carcinogenic Bacterium in Colorectal Cancer: From Association to Causality

Mucosal bacterial dysbiosis in patients with nodular lymphoid hyperplasia in the terminal ileum

Shining a Light on Colibactin Biology

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