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1
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Queen J, Cing Z, Minsky H, Nandi A, Southward T, Ferri J, McMann M, Iyadorai T, Vadivelu J, Roslani A, Loke MF, Wanyiri J, White JR, Drewes JL, Sears CL. Fusobacterium nucleatum is enriched in invasive biofilms in colorectal cancer. NPJ Biofilms Microbiomes 2025; 11:81. [PMID: 40394001 PMCID: PMC12092649 DOI: 10.1038/s41522-025-00717-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 05/01/2025] [Indexed: 05/22/2025] Open
Abstract
Fusobacterium nucleatum is an oral bacterium known to colonize colorectal tumors, where it is thought to play an important role in cancer progression. Recent advances in sequencing and phenotyping of F. nucleatum have revealed important differences at the subspecies level, but whether these differences impact the overall tumor ecology, and tumorigenesis itself, remain poorly understood. In this study, we sought to characterize Fusobacteria in the tumor microbiome of a cohort of individuals with CRC through a combination of molecular, spatial, and microbiologic analyses. We assessed for relative abundance of F. nucleatum in tumors compared to paired normal tissue, and correlated abundance with clinical and pathological features. We demonstrate striking enrichment of F. nucleatum and the recently discovered subspecies animalis clade 2 (Fna C2) specifically in colon tumors that have biofilms, highlighting the importance of complex community partnerships in the pathogenesis of this important organism.
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Affiliation(s)
- Jessica Queen
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Zam Cing
- University of Maryland Baltimore County, Baltimore, MD, USA
| | - Hana Minsky
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Asmita Nandi
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | - Madison McMann
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | | | | | - Jane Wanyiri
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Julia L Drewes
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Cynthia L Sears
- Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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2
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Chu YL, Georgeson P, Clendenning M, Mahmood K, Walker R, Como J, Joseland S, Preston SG, Rice T, Lynch BM, Milne RL, Southey MC, Giles GG, Phipps AI, Hopper JL, Win AK, Rosty C, Macrae FA, Winship I, Jenkins MA, Buchanan DD, Joo JE. Intratumoural pks +Escherichia coli is associated with risk of metachronous colorectal cancer and adenoma development in people with Lynch syndrome. EBioMedicine 2025; 114:105661. [PMID: 40158390 PMCID: PMC11995779 DOI: 10.1016/j.ebiom.2025.105661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 03/07/2025] [Accepted: 03/07/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND The adverse gut microbiome may underlie the variability in risks of colorectal cancer (CRC) and metachronous CRC in people with Lynch syndrome (LS). The role of pks+/-Escherichia coli (pks+/-E. coli), Enterotoxigenic Bacteroides fragilis (ETBF), and Fusobacterium nucleatum (Fn) in CRCs and adenomas in people with LS is unknown. METHODS A total of 358 LS cases, including 386 CRCs, 90 adenomas, 195 normal colonic mucosa DNA from the Australasian Colon Cancer Family Registry were tested using multiplex TaqMan qPCR. Logistic regression was used to compare the intratumoural prevalence of each bacteria in Lynch CRCs with 1336 sporadic CRCs. Cox proportional-hazards regression estimated the associations of each bacteria with the risk of metachronous CRC and neoplasia. FINDINGS Pks+ E. coli (odds ratio [95% confidence interval] = 1.60 [1.08-2.35], P = 0.017), pks-E. coli (3.87 [2.58-5.80], P < 0.001) and Fn (19.47 [13.32-28.87], P < 0.001) were significantly enriched in LS CRCs when compared with sporadic CRCs. Pks+ E. coli in the initial CRC was associated with an increased risk of metachronous CRC (hazard ratio [95% confidence interval] = 2.32 [1.29-4.17], P = 0.005) and metachronous colorectal neoplasia (1.51 [1.02-2.23], P = 0.040) when compared with CRCs without pks+ E. coli. INTERPRETATION Pks+ E. coli, pks-E. coli, and Fn are enriched within LS CRCs, suggesting possible roles in CRC development in LS. Having intratumoural pks+ E. coli is associated with increased risk of metachronous CRC, suggesting that, if validated, people with LS might benefit from pks+ E. coli screening and eradication. FUNDING This work was funded by an NHMRC Investigator grant (GNT1194896) and a Cancer Australia/Cancer Council NSW co-funded grant (GNT2012914).
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Affiliation(s)
- Yen Lin Chu
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Peter Georgeson
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Mark Clendenning
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Khalid Mahmood
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Melbourne Bioinformatics, The University of Melbourne, Melbourne, Victoria, Australia
| | - Romy Walker
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Julia Como
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Sharelle Joseland
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Susan G Preston
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Toni Rice
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia
| | - Brigid M Lynch
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Melissa C Southey
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Amanda I Phipps
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
| | - John L Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Aung K Win
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Christophe Rosty
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; University of Queensland, Brisbane, Queensland, Australia; Envoi Specialist Pathologists, Brisbane, Queensland, Australia
| | - Finlay A Macrae
- Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, Victoria, Australia; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
| | - Ingrid Winship
- Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia
| | - Jihoon E Joo
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia; Collaborative Centre for Genomic Cancer Medicine, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Victoria, Australia.
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Zhang S, Huang J, Jiang Z, Tong H, Ma X, Liu Y. Tumor microbiome: roles in tumor initiation, progression, and therapy. MOLECULAR BIOMEDICINE 2025; 6:9. [PMID: 39921821 PMCID: PMC11807048 DOI: 10.1186/s43556-025-00248-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 01/06/2025] [Accepted: 01/21/2025] [Indexed: 02/10/2025] Open
Abstract
Over the past few years, the tumor microbiome is increasingly recognized for its multifaceted involvement in cancer initiation, progression, and metastasis. With the application of 16S ribosomal ribonucleic acid (16S rRNA) sequencing, the intratumoral microbiome, also referred to as tumor-intrinsic or tumor-resident microbiome, has also been found to play a significant role in the tumor microenvironment (TME). Understanding their complex functions is critical for identifying new therapeutic avenues and improving treatment outcomes. This review first summarizes the origins and composition of these microbial communities, emphasizing their adapted diversity across a diverse range of tumor types and stages. Moreover, we outline the general mechanisms by which specific microbes induce tumor initiation, including the activation of carcinogenic pathways, deoxyribonucleic acid (DNA) damage, epigenetic modifications, and chronic inflammation. We further propose the tumor microbiome may evade immunity and promote angiogenesis to support tumor progression, while uncovering specific microbial influences on each step of the metastatic cascade, such as invasion, circulation, and seeding in secondary sites. Additionally, tumor microbiome is closely associated with drug resistance and influences therapeutic efficacy by modulating immune responses, drug metabolism, and apoptotic pathways. Furthermore, we explore innovative microbe-based therapeutic strategies, such as engineered bacteria, oncolytic virotherapy, and other modalities aimed at enhancing immunotherapeutic efficacy, paving the way for microbiome-centered cancer treatment frameworks.
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Affiliation(s)
- Shengxin Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Jing Huang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan Province, China
| | - Zedong Jiang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Huan Tong
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Yang Liu
- Day Surgery Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
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Nezhadi J, Kafil HS, Sadrkabir M, Mahdavi F, Moaddab SY, Nouri R, Mohammadzadeh-Asl Y, Sattarpour S, Rezaee MA. The relationship between pathogenic bacteria and different stages of colorectal cancer. Lett Appl Microbiol 2025; 78:ovaf017. [PMID: 39924170 DOI: 10.1093/lambio/ovaf017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/24/2025] [Accepted: 02/07/2025] [Indexed: 02/11/2025]
Abstract
Colorectal cancer (CRC) involves uncontrolled cell growth in the colon and rectum. This study aims to explore the prevalence of key pathogenic bacteria and their role in the progression of CRC, focusing on microbial dysbiosis. This study analyzed 52 stool and tissue samples through polymerase chain reaction (PCR), real-time PCR, and bioinformatics to identify associations between pathogenic bacteria and CRC progression. PCR results revealed a significant association between the Bacteroides fragilis toxin (bft) gene and CRC progression (P = 0.001, r = 0.570). Furthermore, Real-time PCR showed significant differences in the frequency of pks+Escherichia coli in CRC stages 1 (P = 0.03), 2 (P = 0.004), and 3 (P = 0.0002) compared to the control group. Additionally, the frequency of Fusobacterium nucleatum in stage 3 CRC patients was significantly higher than in the control group (P = 0.004) and stage 1 patients (P = 0.01). Furthermore, Streptococcus gallolyticus showed similar significant differences in stage 3 patients (P = 0.004). Bioinformatics analyses using KEGG, Reactome, STRING, and dbSNP highlighted bacteria's roles in colorectal carcinogenesis, emphasizing the need for early identification and management in CRC treatment and prevention strategies. Finally, due to the limitations of the study, the use of more advanced methods and the validation of results through more reliable techniques are essential for future research.
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Affiliation(s)
- Javad Nezhadi
- Student Research Committee, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Mohammad Sadrkabir
- Department of Internal Medicine, Islamic Azad University, Tabriz Branch, 5158913791, Tabriz, Iran
| | - Farshad Mahdavi
- Department of General Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Seyed Yaghoub Moaddab
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Roghayeh Nouri
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Yalda Mohammadzadeh-Asl
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Simin Sattarpour
- Department of Basic Sciences, Faculty of Allied Medical Sciences, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
| | - Mohammad Ahangarzadeh Rezaee
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, 5165665931, Tabriz, Iran
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Queen J, Cing Z, Minsky H, Nandi A, Southward T, Ferri J, McMann M, Iyadorai T, Vadivelu J, Roslani A, Loke MF, Wanyiri J, White JR, Drewes JL, Sears CL. Fusobacterium nucleatum is enriched in invasive biofilms in colorectal cancer. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2024.12.30.630810. [PMID: 39803475 PMCID: PMC11722383 DOI: 10.1101/2024.12.30.630810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Fusobacterium nucleatum is an oral bacterium known to colonize colorectal tumors, where it is thought to play an important role in cancer progression. Recent advances in sequencing and phenotyping of F. nucleatum have revealed important differences at the subspecies level, but whether these differences impact the overall tumor ecology, and tumorigenesis itself, remain poorly understood. In this study, we sought to characterize Fusobacteria in the tumor microbiome of a cohort of individuals with CRC through a combination of molecular, spatial, and microbiologic analyses. We assessed for relative abundance of F. nucleatum in tumors compared to paired normal tissue, and correlated abundance with clinical and pathological features. We demonstrate striking enrichment of F. nucleatum and the recently discovered subspecies animalis clade 2 (Fna C2) specifically in colon tumors that have biofilms, highlighting the importance of complex community partnerships in the pathogenesis of this important organism.
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Affiliation(s)
- Jessica Queen
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Zam Cing
- University of Maryland Baltimore County, Baltimore, MD, USA
| | - Hana Minsky
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Asmita Nandi
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | - Madison McMann
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | | | | | | | | | | | - Julia L Drewes
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cynthia L Sears
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Hwang S, Jo M, Hong JE, Kim WS, Kang DH, Yoo SH, Kang K, Rhee KJ. Caffeic Acid Phenethyl Ester Administration Reduces Enterotoxigenic Bacteroides fragilis-Induced Colitis and Tumorigenesis. Toxins (Basel) 2024; 16:403. [PMID: 39330861 PMCID: PMC11435740 DOI: 10.3390/toxins16090403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/08/2024] [Accepted: 09/13/2024] [Indexed: 09/28/2024] Open
Abstract
The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC).
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Affiliation(s)
- Soonjae Hwang
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
- Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Inchon 21999, Republic of Korea
| | - Minjeong Jo
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea
| | - Ju-Eun Hong
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
| | - Woo-Seung Kim
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
| | - Da-Hye Kang
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
- Department of Obstetrics, Gynecology and Women’s Health, University of Missouri, Columbia, MO 65211, USA
| | - Sang-Hyeon Yoo
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
| | - Kyungsu Kang
- Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea;
| | - Ki-Jong Rhee
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
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Shieh C, Thompson HJ, McLaughlin E, Chiang CW, Hussan H. Advancements in Understanding and Preventing Obesity-Related Colon Cancer. Cancer J 2024; 30:357-369. [PMID: 39312456 DOI: 10.1097/ppo.0000000000000744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
ABSTRACT Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes. We also consider whether those linkages can be disrupted via weight loss therapies, including lifestyle modifications, pharmacotherapy, bariatric surgery, and endobariatrics.
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Affiliation(s)
- Christine Shieh
- From the Department of Gastroenterology, University of California, Davis, Sacramento, CA
| | - Henry J Thompson
- Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO
| | | | - Chien-Wei Chiang
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH
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Shi J, Shen H, Huang H, Zhan L, Chen W, Zhou Z, Lv Y, Xiong K, Jiang Z, Chen Q, Liu L. Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions. Front Microbiol 2024; 15:1395514. [PMID: 38962132 PMCID: PMC11220721 DOI: 10.3389/fmicb.2024.1395514] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/27/2024] [Indexed: 07/05/2024] Open
Abstract
The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.
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Affiliation(s)
- Jianguo Shi
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hexiao Shen
- School of Life Sciences and Health Engineering, Hubei University, Wuhan, China
| | - Hui Huang
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lifang Zhan
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Chen
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuohui Zhou
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yongling Lv
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Kai Xiong
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhiwei Jiang
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qiyi Chen
- Department of Colorectal Disease, Intestinal Microenvironment Treatment Center, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Lei Liu
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Takashima Y, Kawamura H, Okadome K, Ugai S, Haruki K, Arima K, Mima K, Akimoto N, Nowak JA, Giannakis M, Garrett WS, Sears CL, Song M, Ugai T, Ogino S. Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype-high colorectal carcinoma. Clin Microbiol Infect 2024; 30:630-636. [PMID: 38266708 PMCID: PMC11043012 DOI: 10.1016/j.cmi.2024.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 12/04/2023] [Accepted: 01/13/2024] [Indexed: 01/26/2024]
Abstract
OBJECTIVES Data support that enterotoxigenic Bacteroides fragilis (ETBF) harbouring the Bacteroides fragilis toxin (bft) gene may promote colorectal tumourigenesis through the serrated neoplasia pathway. We hypothesized that ETBF may be enriched in colorectal carcinoma subtypes with high-level CpG island methylator phenotype (CIMP-high), BRAF mutation, and high-level microsatellite instability (MSI-high). METHODS Quantitative PCR assays were designed to quantify DNA amounts of Bacteroides fragilis, ETBF, and each bft gene isotype (bft-1, bft-2, or bft-3) in colorectal carcinomas in the Health Professionals Follow-up Study and Nurses' Health Study. We used multivariable-adjusted logistic regression models with the inverse probability weighting method. RESULTS We documented 4476 colorectal cancer cases, including 1232 cases with available bacterial data. High DNA amounts of Bacteroides fragilis and ETBF were positively associated with BRAF mutation (p ≤ 0.0003), CIMP-high (p ≤ 0.0002), and MSI-high (p < 0.0001 and p = 0.01, respectively). Multivariable-adjusted odds ratios (with 95% confidence interval) for high Bacteroides fragilis were 1.40 (1.06-1.85) for CIMP-high and 2.14 (1.65-2.77) for MSI-high, but 1.02 (0.78-1.35) for BRAF mutation. Multivariable-adjusted odds ratios for high ETBF were 2.00 (1.16-3.45) for CIMP-high and 2.86 (1.64-5.00) for BRAF mutation, but 1.09 (0.67-1.76) for MSI-high. Neither Bacteroides fragilis nor ETBF was associated with colorectal cancer-specific or overall survival. DISCUSSION The tissue abundance of Bacteroides fragilis is associated with CIMP-high and MSI-high, whereas ETBF abundance is associated with CIMP-high and BRAF mutation in colorectal carcinoma. Our findings support the aetiological relevance of Bacteroides fragilis and ETBF in the serrated neoplasia pathway.
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Affiliation(s)
- Yasutoshi Takashima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Hidetaka Kawamura
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kazuo Okadome
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Satoko Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kosuke Mima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Wendy S Garrett
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Cynthia L Sears
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cancer Immunology Program, Dana-Farber Harvard Cancer Centre, Boston, MA, USA.
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10
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Joo JE, Chu YL, Georgeson P, Walker R, Mahmood K, Clendenning M, Meyers AL, Como J, Joseland S, Preston SG, Diepenhorst N, Toner J, Ingle DJ, Sherry NL, Metz A, Lynch BM, Milne RL, Southey MC, Hopper JL, Win AK, Macrae FA, Winship IM, Rosty C, Jenkins MA, Buchanan DD. Intratumoral presence of the genotoxic gut bacteria pks + E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer. Br J Cancer 2024; 130:728-740. [PMID: 38200234 PMCID: PMC10912205 DOI: 10.1038/s41416-023-02554-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 12/07/2023] [Accepted: 12/11/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum). METHODS We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR. RESULTS Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01). CONCLUSION Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.
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Affiliation(s)
- Jihoon E Joo
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Yen Lin Chu
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Peter Georgeson
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Romy Walker
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Khalid Mahmood
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
- Melbourne Bioinformatics, The University of Melbourne, Melbourne, VIC, Australia
| | - Mark Clendenning
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Aaron L Meyers
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Julia Como
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Sharelle Joseland
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Susan G Preston
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Natalie Diepenhorst
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Julie Toner
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
| | - Danielle J Ingle
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
| | - Norelle L Sherry
- Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
- Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia
| | - Andrew Metz
- Endoscopy Unit, Department of Gastroenterology and Hepatology, The Royal Melbourne Hospital, Parkville, VIC, Australia
- Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia
| | - Brigid M Lynch
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
| | - Roger L Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia
| | - Melissa C Southey
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia
- Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia
| | - John L Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Aung Ko Win
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Finlay A Macrae
- Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, VIC, Australia
- Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia
- Department of Medicine, The University of Melbourne, Parkville, VIC, Australia
| | - Ingrid M Winship
- Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia
- Department of Medicine, The University of Melbourne, Parkville, VIC, Australia
| | - Christophe Rosty
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia
- Envoi Specialist Pathologists, Brisbane, QLD, Australia
- University of Queensland, Brisbane, QLD, Australia
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia.
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia.
- Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.
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11
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Elahi Z, Shariati A, Bostanghadiri N, Dadgar-Zankbar L, Razavi S, Norzaee S, Vazirbani Arasi S, Darban-Sarokhalil D. Association of Lactobacillus, Firmicutes, Bifidobacterium, Clostridium, and Enterococcus with colorectal cancer in Iranian patients. Heliyon 2023; 9:e22602. [PMID: 38089982 PMCID: PMC10711133 DOI: 10.1016/j.heliyon.2023.e22602] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 11/08/2023] [Accepted: 11/15/2023] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the primary causes of cancer-associated deaths worldwide, and growing evidence shows that alteration in the gut microbiota may be a contributing factor to the development and progression of the disease. This study investigates the correlation between CRC and specific intestinal microbiota abundance, including Firmicutes, Lactobacillus, Enterococcus, Clostridium, and Bifidobacterium. MATERIAL AND METHODS In this study, 100 CRC samples and adjacent normal tissues were obtained from Iranian patients. Afterward, we assessed the abundance of the mentioned bacteria in matched tumor and normal tissue samples from 100 CRC patients, by TaqMan quantitative real-time polymerase chain reaction (qPCR). RESULTS Most of the patients (55 %) had grade II cancer (moderately differentiated), followed by grade III (poorly Differentiated) in 19 %, and the distribution of the tumor location was 65 % in the colon and 35 % in the rectum. Our research showed a substantial difference in the relative abundance of specific bacteria in tumors and healthy tissues. To this end, four genera of bacteria, including Bifidobacterium, Lactobacillus, Clostridium, and Firmicutes, exhibited statistically significant reductions in tumor tissues compared to adjacent normal tissue (p < 0.05). Conversely, Enterococcus demonstrated a statistically significant increase in tumor tissue samples (p < 0.05). Noteworthy, statistical analysis revealed a significant relationship between Enterococcus and prior cancer (p < 0.05). CONCLUSIONS These findings provide significant insight into the complex association between the gut microbiota and CRC and may pave the way for future research on novel screening methods, preventive measures, and therapeutic strategies targeting the gut microbiota in CRC patients.
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Affiliation(s)
- Zahra Elahi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Aref Shariati
- Student Research Committee, Khomein University of Medical Sciences, Khomein, Iran
- Molecular and Medicine Research Centre, Khomein University of Medical Sciences, Khomein, Iran
| | - Narjess Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Leila Dadgar-Zankbar
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Samira Norzaee
- Research Center for Environmental Health Technology, Iran University of Medical Sciences, Tehran, Iran
- Department of Environmental Health Engineering, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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12
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Xiaofeng N, Jian C, Jingjing W, Zhanbo Q, Yifei S, Jing Z, Shuwen H. Correlation of gut microbiota with leukopenia after chemotherapy in patients with colorectal cancer. BMC Microbiol 2023; 23:349. [PMID: 37978347 PMCID: PMC10655349 DOI: 10.1186/s12866-023-03067-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 10/16/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND The most common toxic side effect after chemotherapy, one of the main treatments for colorectal cancer (CRC), is myelosuppression. OBJECTIVE To analyze the correlation between gut microbiota and leukopenia after chemotherapy in CRC patients. METHODS Stool samples were collected from 56 healthy individuals and 55 CRC patients. According to the leukocytes levels in peripheral blood, the CRC patients were divided into hypoleukocytes group (n = 13) and normal leukocytes group (n = 42). Shannon index, Simpson index, Ace index, Chao index and Coverage index were used to analyze the diversity of gut microbiota. LDA and Student's t-test(St test) were used for analysis of differences. Six machine learning algorithms, including logistic regression (LR) algorithm, random forest (RF) algorithm, neural network (NN) algorithm, support vector machine (SVM) algorithm, catboost algorithm and gradient boosting tree algorithm, were used to construct the prediction model of gut microbiota with leukopenia after chemotherapy for CRC. RESULTS Compared with healthy group, the microbiota alpha diversity of CRC patients was significantly decreased (p < 0.05). After analyzing the gut microbiota differences of the two groups, 15 differential bacteria, such as Bacteroides, Faecalibacterium and Streptococcus, were screened. RF prediction model had the highest accuracy, and the gut microbiota with the highest predictive value were Peptostreptococcus, Faecalibacterium, and norank_f__Ruminococcaceae, respectively. Compared with normal leukocytes group, the microbiota alpha diversity of hypoleukocytes group was significantly decreased (p < 0.05). The proportion of Escherichia-Shigella was significantly decreased in the hypoleukocytes group. After analyzing the gut microbiota differences of the two groups, 9 differential bacteria, such as Escherichia-Shigella, Fusicatenibacter and Cetobacterium, were screened. RF prediction model had the highest accuracy, and the gut microbiota with the highest predictive value were Fusicatenibacte, Cetobacterium, and Paraeggerthella. CONCLUSION Gut microbiota is related to leukopenia after chemotherapy. The gut microbiota may provide a novel method for predicting myelosuppression after chemotherapy in CRC patients.
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Affiliation(s)
- Ni Xiaofeng
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China
| | - Chu Jian
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China
- Fifth School of Clinical Medicine of Zhejiang, Huzhou Central Hospital, Chinese Medical University, Huzhou, China
| | - Wang Jingjing
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China
| | - Qu Zhanbo
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China
- Fifth School of Clinical Medicine of Zhejiang, Huzhou Central Hospital, Chinese Medical University, Huzhou, China
| | - Song Yifei
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China
| | - Zhuang Jing
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China.
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, Huzhou, China.
| | - Han Shuwen
- Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Huzhou, China.
- Fifth School of Clinical Medicine of Zhejiang, Huzhou Central Hospital, Chinese Medical University, Huzhou, China.
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of Huzhou, Huzhou, China.
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13
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Dadgar-Zankbar L, Shariati A, Bostanghadiri N, Elahi Z, Mirkalantari S, Razavi S, Kamali F, Darban-Sarokhalil D. Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer. Infect Agent Cancer 2023; 18:48. [PMID: 37644520 PMCID: PMC10463534 DOI: 10.1186/s13027-023-00523-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 08/02/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/β-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC. MATERIALS AND METHODS B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed. RESULTS The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample. CONCLUSION B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.
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Affiliation(s)
- Leila Dadgar-Zankbar
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Aref Shariati
- Molecular and Medicine Research Center, Khomein University of Medical Sciences, Khomein, Iran
- Student Research Committee, Khomein University of Medical Sciences, Khomein, Iran
| | - Narjess Bostanghadiri
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Elahi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shiva Mirkalantari
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Kamali
- Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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14
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Queen J, Shaikh F, Sears CL. Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation. NATURE CANCER 2023; 4:1083-1094. [PMID: 37525016 DOI: 10.1038/s43018-023-00602-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 06/21/2023] [Indexed: 08/02/2023]
Abstract
The intersection of the microbiota and cancer and the mechanisms that define these interactions are a fascinating, rapidly evolving area of cancer biology and therapeutics. Here we present recent insights into the mechanisms by which specific bacteria or their communities contribute to carcinogenesis and discuss the bidirectional interplay between microbiota and host gene or epigenome signaling. We conclude with comments on manipulation of the microbiota for the therapeutic benefit of patients with cancer.
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Affiliation(s)
- Jessica Queen
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Fyza Shaikh
- Cancer Immunology Program, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cynthia L Sears
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Cancer Immunology Program, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Microbiology and Molecular Immunology, Bloomberg School of Public Health, Baltimore, MD, USA.
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15
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Pös O, Styk J, Buglyó G, Zeman M, Lukyova L, Bernatova K, Hrckova Turnova E, Rendek T, Csók Á, Repiska V, Nagy B, Szemes T. Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer. Int J Mol Sci 2023; 24:10520. [PMID: 37445698 DOI: 10.3390/ijms241310520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/15/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile.
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Affiliation(s)
- Ondrej Pös
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Geneton Ltd., 841 04 Bratislava, Slovakia
| | - Jakub Styk
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Geneton Ltd., 841 04 Bratislava, Slovakia
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
| | - Gergely Buglyó
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Michal Zeman
- Comenius University Science Park, 841 04 Bratislava, Slovakia
| | - Lydia Lukyova
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
| | - Kamila Bernatova
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
| | - Evelina Hrckova Turnova
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Slovgen Ltd., 841 04 Bratislava, Slovakia
| | - Tomas Rendek
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
| | - Ádám Csók
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Vanda Repiska
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia
- Medirex Group Academy, n.p.o., 949 05 Nitra, Slovakia
| | - Bálint Nagy
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Department of Human Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Tomas Szemes
- Comenius University Science Park, 841 04 Bratislava, Slovakia
- Geneton Ltd., 841 04 Bratislava, Slovakia
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, 842 05 Bratislava, Slovakia
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16
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Gu M, Yin W, Zhang J, Yin J, Tang X, Ling J, Tang Z, Yin W, Wang X, Ni Q, Zhu Y, Chen T. Role of gut microbiota and bacterial metabolites in mucins of colorectal cancer. Front Cell Infect Microbiol 2023; 13:1119992. [PMID: 37265504 PMCID: PMC10229905 DOI: 10.3389/fcimb.2023.1119992] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 05/03/2023] [Indexed: 06/03/2023] Open
Abstract
Colorectal cancer (CRC) is a major health burden, accounting for approximately 10% of all new cancer cases worldwide. Accumulating evidence suggests that the crosstalk between the host mucins and gut microbiota is associated with the occurrence and development of CRC. Mucins secreted by goblet cells not only protect the intestinal epithelium from microorganisms and invading pathogens but also provide a habitat for commensal bacteria. Conversely, gut dysbiosis results in the dysfunction of mucins, allowing other commensals and their metabolites to pass through the intestinal epithelium, potentially triggering host responses and the subsequent progression of CRC. In this review, we summarize how gut microbiota and bacterial metabolites regulate the function and expression of mucin in CRC and novel treatment strategies for CRC.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiangjun Wang
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Qing Ni
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Yunxiang Zhu
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Tuo Chen
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, China
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17
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Ait-Zenati F, Djoudi F, Mehelleb D, Madaoui M. Involvement of the human microbiome in frequent cancers, current knowledge and carcinogenesis mechanisms. Bull Cancer 2023:S0007-4551(23)00092-9. [PMID: 36959041 DOI: 10.1016/j.bulcan.2023.01.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 01/10/2023] [Accepted: 01/31/2023] [Indexed: 03/25/2023]
Abstract
The human body is home to a complex microbial community, living in symbiosis. However, when an imbalance occurs, known as dysbiosis, it can lead to organic diseases such as cancers. Helicobacter pylori is commonly recognized as the causative agent of gastric cancer. Numerous studies have explored the potential role of other microorganisms in cancers. For example, the role of intestinal microbiota in the hepatocellular carcinoma formation and progression, the microbiota in breast cancer and the interaction between the microbiome and TP53 in human lung carcinogenesis. In this review, we highlight the latest findings on the microbiome involved in the most common cancers and the suggested mechanisms of carcinogenesis.
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Affiliation(s)
- Fazia Ait-Zenati
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria
| | - Ferhat Djoudi
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria.
| | - Dalila Mehelleb
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria
| | - Menad Madaoui
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria
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18
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Wang DN, Ni JJ, Li JH, Gao YQ, Ni FJ, Zhang ZZ, Fang JY, Lu J, Yao YF. Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation. PLoS Pathog 2023; 19:e1011189. [PMID: 36812247 PMCID: PMC9987831 DOI: 10.1371/journal.ppat.1011189] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 03/06/2023] [Accepted: 02/07/2023] [Indexed: 02/24/2023] Open
Abstract
Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.
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Affiliation(s)
- Dan-Ni Wang
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jin-Jing Ni
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian-Hui Li
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Phage, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Ya-Qi Gao
- State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fang-Jing Ni
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhen-Zhen Zhang
- Department of Pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing-Yuan Fang
- State Key Laboratory for Oncogenes and Related Genes; Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Lu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- * E-mail: (JL); (Y-FY)
| | - Yu-Feng Yao
- Laboratory of Bacterial Pathogenesis, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China
- * E-mail: (JL); (Y-FY)
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19
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Lo CH, Wu DC, Jao SW, Wu CC, Lin CY, Chuang CH, Lin YB, Chen CH, Chen YT, Chen JH, Hsiao KH, Chen YJ, Chen YT, Wang JY, Li LH. Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas. J Biomed Sci 2022; 29:88. [PMID: 36303164 PMCID: PMC9615364 DOI: 10.1186/s12929-022-00869-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 10/18/2022] [Indexed: 12/02/2022] Open
Abstract
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.
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Affiliation(s)
- Chia-Hui Lo
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Wen Jao
- Division of Colon and Rectal Surgery, Tri-Service General Hospital, Taipei, Taiwan
| | - Chang-Chieh Wu
- Division of Colon and Rectal Surgery, Tri-Service General Hospital, Taipei, Taiwan
| | - Chung-Yen Lin
- Institute of Information Science, Academia Sinica, Taipei, Taiwan
| | | | - Ya-Bo Lin
- Institute of Information Science, Academia Sinica, Taipei, Taiwan
| | - Chien-Hsiun Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Ying-Ting Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Jiann-Hwa Chen
- Scool of Medicine, Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
| | - Koung-Hung Hsiao
- Department of Colorectal Surgery, Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan
| | - Ying-Ju Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Yuan-Tsong Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.
| | - Ling-Hui Li
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
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20
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Status of Microbiota in Odontogenic Inflammatory Lesions and Dental Surgery Procedures Performed on an Outpatient Basis. Antibiotics (Basel) 2022; 11:antibiotics11081025. [PMID: 36009894 PMCID: PMC9404737 DOI: 10.3390/antibiotics11081025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 01/27/2023] Open
Abstract
Inflammations of the facial part of the skull are most commonly caused by a bacterial infection. They are a frequently occurring pathological process, which results from a rich bacterial flora of the oral cavity, as well as diseased teeth and periodontal tissues. These inflammations have a primarily mixed character with the prevalence of anaerobic bacteria. Gangrene of the dental pulp is the most common odontogenic cause. In the case of inflammations of oral tissues an early and corrective treatment results in quick recovery. The purpose of this work was to assess the efficiency of empirical antibiotic therapy applied in patients with inflammations of oral tissues on the basis of a drug susceptibility profile of bacteria isolated from material extracted from inflammatory lesions. The research material consisted of smears collected from patients with existing acute inflammations in the oral cavity. The smear was collected from the bottom of the lesion after its prior surgical treatment and pus evacuation, and again, 7 days after surgery. In patients with acute odontogenic inflammations the recommended first-line therapy are extended-spectrum penicillins, characterized by a low risk of side effects and strong antimicrobial activity. In the study group, both clindamycin and amoxicillin exhibited high efficiency in treating acute odontogenic inflammatory lesions in the oral cavity.
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21
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Scott N, Whittle E, Jeraldo P, Chia N. A systemic review of the role of enterotoxic Bacteroides fragilis in colorectal cancer. Neoplasia 2022; 29:100797. [PMID: 35461079 PMCID: PMC9046963 DOI: 10.1016/j.neo.2022.100797] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 03/25/2022] [Accepted: 04/01/2022] [Indexed: 12/13/2022]
Abstract
Enterotoxigenic Bacteroides fragilis (ETBF) has received significant attention for a possible association with, or causal role in, colorectal cancer (CRC). The goal of this review was to assess the status of the published evidence supporting (i) the association between ETBF and CRC and (ii) the causal role of ETBF in CRC. PubMed and Scopus searches were performed in August 2021 to identify human, animal, and cell studies pertaining to the role of ETBF in CRC. Inclusion criteria included the use of cell lines, mice, exposure to BFT or ETBF, and detection of bft. Review studies were excluded, and studies were limited to the English language. Quality of study design and risk of bias analysis was performed on the cell, animal, and human studies using ToxRTools, SYRCLE, and NOS, respectively. Ninety-five eligible studies were identified, this included 22 human studies, 24 animal studies, 43 cell studies, and 6 studies that included both cells and mice studies. We found that a large majority of studies supported an association or causal role of ETBF in CRC, as well as high levels of study bias was detected in the in vitro and in vivo studies. The high-level heterogeneity in study design and reporting made it difficult to synthesize these findings into a unified conclusion, suggesting that the need for future studies that include improved mechanistic models, longitudinal in vitro and in vivo evidence, and appropriate control of confounding factors will be required to confirm whether ETBF has a direct role in CRC etiopathogenesis.
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Affiliation(s)
- Nancy Scott
- Bioinformatics and Computational Biology, University of Minnesota, 111 South Broadway, Rochester, MN 55904, USA
| | - Emma Whittle
- Department of Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA
| | - Patricio Jeraldo
- Department of Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA
| | - Nicholas Chia
- Department of Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Microbiome Program, Center for Individualized Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
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22
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Microbiome Analysis in Patients with Colorectal Cancer by 16S Ribosomal RNA Sequencing in the Southeast of Iran. Jundishapur J Microbiol 2022. [DOI: 10.5812/jjm-121119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Emerging evidence suggests that dysbiosis of the colon microbiome may be involved in CRC development. Objectives: The present study aimed to compare the composition and diversity of the colon microbiome by high-throughput 16S ribosomal RNA (rRNA) sequencing between CRC patients and healthy controls. Microbiome composition and diversity were also examined based on gender. Methods: The colon microbiome richness and diversity of samples from 17 CRC patients and 13 healthy controls were analyzed by 16S rRNA sequencing. Alpha and beta diversity were calculated to determine the differences in colon microbiome diversity. Results: Alpha and beta diversity showed significant differences between the CRC and healthy control groups regarding the microbiome. Our results showed that CRC samples had the highest richness and diversity. The total number (P ≤ 0.01), phylogenetic diversity (P ≤ 0.01), Chao1 (P ≤ 0.01), Shannon (P ≤ 0.05), and Simpson (P ≤ 0.01) indices were significantly higher in the CRC group than in the healthy control group. In addition, the comparison between females and males showed that the microbiome diversity was higher in the CRC female (CRC-F) group than in other groups. Prevotella, Fusobacterium, Akkermansia, Leptotrichia, Streptococcus, and ParaBacteroides were more commonly observed in the CRC group, while Bacteroides, Enterobacteriaceae (unknown genus), Ruminococcus, and Campylobacter were more commonly observed in the healthy control group. Conclusions: This study showed differences between the CRC and healthy control groups regarding the diversity and composition of the colon microbiome, suggesting a contribution of the microbiome in the development and progression of CRC.
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23
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Yu L, Zhao G, Wang L, Zhou X, Sun J, Li X, Zhu Y, He Y, Kofonikolas K, Bogaert D, Dunlop M, Zhu Y, Theodoratou E, Li X. A systematic review of microbial markers for risk prediction of colorectal neoplasia. Br J Cancer 2022; 126:1318-1328. [PMID: 35292756 PMCID: PMC9042911 DOI: 10.1038/s41416-022-01740-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 12/23/2021] [Accepted: 02/03/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Substantial evidence indicates that dysbiosis of the gut microbial community is associated with colorectal neoplasia. This review aims to systematically summarise the microbial markers associated with colorectal neoplasia and to assess their predictive performance. METHODS A comprehensive literature search of MEDLINE and EMBASE databases was performed to identify eligible studies. Observational studies exploring the associations between microbial biomarkers and colorectal neoplasia were included. We also included prediction studies that constructed models using microbial markers to predict CRC and adenomas. Risk of bias for included observational and prediction studies was assessed. RESULTS Forty-five studies were included to assess the associations between microbial markers and colorectal neoplasia. Nine faecal microbiotas (i.e., Fusobacterium, Enterococcus, Porphyromonas, Salmonella, Pseudomonas, Peptostreptococcus, Actinomyces, Bifidobacterium and Roseburia), two oral pathogens (i.e., Treponema denticola and Prevotella intermedia) and serum antibody levels response to Streptococcus gallolyticus subspecies gallolyticus were found to be consistently associated with colorectal neoplasia. Thirty studies reported prediction models using microbial markers, and 83.3% of these models had acceptable-to-good discrimination (AUROC > 0.75). The results of predictive performance were promising, but most of the studies were limited to small number of cases (range: 9-485 cases) and lack of independent external validation (76.7%). CONCLUSIONS This review provides insight into the evidence supporting the association between different types of microbial species and their predictive value for colorectal neoplasia. Prediction models developed from case-control studies require further external validation in high-quality prospective studies. Further studies should assess the feasibility and impact of incorporating microbial biomarkers in CRC screening programme.
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Affiliation(s)
- Lili Yu
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Gang Zhao
- Center for Disease Control and Prevention of Hangzhou, Hangzhou, China
| | - Lijuan Wang
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Zhou
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Sun
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinxuan Li
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yingshuang Zhu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Yazhou He
- Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, China
| | | | - Debby Bogaert
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Malcolm Dunlop
- Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Yimin Zhu
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK
- Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Xue Li
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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24
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Nouri R, Hasani A, Asgharzadeh M, Sefidan FY, Hemmati F, Rezaee MA. Roles of gut microbiota in colorectal carcinogenesis providing a perspective for early diagnosis and treatment. Curr Pharm Biotechnol 2022; 23:1569-1580. [PMID: 35255786 DOI: 10.2174/1389201023666220307112413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 12/29/2021] [Accepted: 01/03/2022] [Indexed: 12/02/2022]
Abstract
Colorectal cancer (CRC) is the third most prevalent malignant neoplasm in the world. CRC is influenced by both environmental and genetic factors. Through toxin-mediated DNA damage and promotion of persistent dysregulated inflammation, the gut microbiota plays a crucial role in the development of CRC. In this review, we discussed the correlation between the bacterial microbiota and CRC carcinogenesis as well as the mechanism by which Streptococcus bovis/gallolyticus, Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli can cause CRC.
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Affiliation(s)
- Roghayeh Nouri
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alka Hasani
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Asgharzadeh
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Yeganeh Sefidan
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Hemmati
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Ahangarzadeh Rezaee
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Clinical Research Development Unit of Children Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
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25
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Shaw S, Berry S, Thomson J, Murray GI, El-Omar E, Hold GL. Gut Mucosal Microbiome Signatures of Colorectal Cancer Differ According to BMI Status. Front Med (Lausanne) 2022; 8:800566. [PMID: 35211486 PMCID: PMC8861504 DOI: 10.3389/fmed.2021.800566] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 12/23/2021] [Indexed: 01/14/2023] Open
Abstract
Background Carrying excess body weight is a strong risk factor for colorectal cancer (CRC) development with ~11% of CRC cases in Europe linked to being overweight. The mechanisms through which excess body weight influences CRC development are not well understood but studies suggest the involvement of the presence of chronic low-grade inflammation and changes in the gut microbiota are involved. Aim To compare the mucosal associated microbiota of patients with CRC to understand whether carrying excess body weight was associated with a unique CRC microbial signature. Methods Microbiota signatures from colonic mucosal biopsies of CRC lesions and adjacent normal mucosal samples from 20 patients with overt CRC were compared with 11 healthy controls to see if having a BMI of >25 kg/m2 influenced colonic microbial composition. Results Colonic mucosa samples from patients with CRC confirmed previously reported over-abundance of Fusobacteria associated with CRC but also an increase in Fusobacteria and Prevotella were associated with a BMI of >25 kg/m2. Correlation analysis of bacterial taxa indicated co-exclusive relationships were more common in CRC patients with a BMI >25 kg/m2 with an increase in transphylum relationships also seen in this patient group. Conclusions The findings suggest that gut microbiota composition in patients with CRC is influenced by BMI status. Further understanding/defining these differences will provide valuable information in terms of developing novel pre-onset screening and providing post-manifestation therapeutic intervention.
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Affiliation(s)
- Sophie Shaw
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Susan Berry
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - John Thomson
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Graeme I Murray
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Emad El-Omar
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Georgina L Hold
- School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
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26
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Ren L. Circular RNA PIP5K1A act as microRNA-552-3p sponge to regulates inflammation, oxidative damage in glucolipotoxicity-induced pancreatic INS-1 β-cells via Janus kinase 1. Bioengineered 2022; 13:5724-5736. [PMID: 35184688 PMCID: PMC8974055 DOI: 10.1080/21655979.2021.2022076] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Elevated level of glucolipotoxicity induces the loss of pancreatic β-cells functions and plays an important role in the development of type 2 diabetes (T2DM). Previous studies have indicated the importance of developing therapies against T2DM, while circular RNA (circRNA) has gained attraction as a modulator of pancreatic β-cell function. In the present study role of circPIP5K1A in dysfunctional β cells and mouse pancreas was comprehensively analyzed. INS-1E, as it has close similarity with naïve pancreatic β-cells, and clinical samples of T2DM patients were used to investigate the effect of circPIP5K1A, miR-552-3p, and Janus kinase 1 (JAK1). While, INS-1E cells were exposed to PAHG conditions (0.5 mM palmitic acid and 28 mM glucose) as studies have suggested that increased level of fatty acid and glucose resulted in autophagy activation of pancreatic β-cells that leads to T2DM. Key player of JAK1-STAT3 pathway and the level of Reactive Oxygen Species, inflammatory factors, and insulin secretion was detected to analyze the of the active association of circPIP5K1A, miR-552-3p with JAK1pathway. Our study has revealed the elevated level ofcircPIP5K1A and JAK1, but reduced level of miR-552-3pin the serum of T2DM patients. Furthermore, we also found that reduced expression ofcircPIP5K1A leads to decreased rate of inflammation, oxidative damage and apoptosisinINS-1E cells induced by glucolipotoxicity. CircPIP5K1A was available to competitively combine with miR-552-3p, while whose direct target was JAK1. In conclusion, our study suggested a novel involvement of circPIP5K1A in a cross talk between miR5523p/JAK1/STAT3 pathways in β-cells as a new therapeutic target for T2DM.
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Affiliation(s)
- Lei Ren
- Department of Endocrinology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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27
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Seely KD, Morgan AD, Hagenstein LD, Florey GM, Small JM. Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia. Cancers (Basel) 2022; 14:1019. [PMID: 35205767 PMCID: PMC8870662 DOI: 10.3390/cancers14041019] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/14/2022] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
While the gut microbiome is composed of numerous bacteria, specific bacteria within the gut may play a significant role in carcinogenesis, progression, and metastasis of colorectal carcinoma (CRC). Certain microbial species are known to be associated with specific cancers; however, the interrelationship between bacteria and metastasis is still enigmatic. Mounting evidence suggests that bacteria participate in cancer organotropism during solid tumor metastasis. A critical review of the literature was conducted to better characterize what is known about bacteria populating a distant site and whether a tumor depends upon the same microenvironment during or after metastasis. The processes of carcinogenesis, tumor growth and metastatic spread in the setting of bacterial infection were examined in detail. The literature was scrutinized to discover the role of the lymphatic and venous systems in tumor metastasis and how microbes affect these processes. Some bacteria have a potent ability to enhance epithelial-mesenchymal transition, a critical step in the metastatic cascade. Bacteria also can modify the microenvironment and the local immune profile at a metastatic site. Early targeted antibiotic therapy should be further investigated as a measure to prevent metastatic spread in the setting of bacterial infection.
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Affiliation(s)
- Kevin D. Seely
- College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA; (A.D.M.); (L.D.H.)
| | - Amanda D. Morgan
- College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA; (A.D.M.); (L.D.H.)
| | - Lauren D. Hagenstein
- College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA; (A.D.M.); (L.D.H.)
| | - Garrett M. Florey
- College of Osteopathic Medicine, Rocky Vista University, Parker, CO 80134, USA;
| | - James M. Small
- Department of Biomedical Sciences, Rocky Vista University, Parker, CO 80134, USA;
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Tortora SC, Bodiwala VM, Quinn A, Martello LA, Vignesh S. Microbiome and colorectal carcinogenesis: Linked mechanisms and racial differences. World J Gastrointest Oncol 2022; 14:375-395. [PMID: 35317317 PMCID: PMC8918999 DOI: 10.4251/wjgo.v14.i2.375] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/26/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of “the hallmarks of cancer”, and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of Bacteroides, Prevotella, Escherichia coli, enterotoxigenic Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Fusobacterium nucleatum (F. nucleatum) and Clostridium difficile. Higher levels of Bacteroides have been found in African American (AA) compared to Caucasian American (CA) patients. Pro-inflammatory bacteria such as F. nucleatum and Enterobacter species were significantly higher in AAs. Also, AA patients have been shown to have decreased microbial diversity compared to CA patients. Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age, race and body mass index may help predict healthy colon vs one with adenomas or carcinomas. Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites. This condition causes increased systemic inflammation, immune dysregulation, gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis. Periodontal-associated bacteria such as Fusobacterium, Prevotella, Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients. Therefore, a deeper understanding of the association between oral and gastrointestinal bacterial profile, in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race, may play a pivotal role in predicting incidence, prognosis, and lead to the development of new treatments.
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Affiliation(s)
- Sofia C Tortora
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Vimal M Bodiwala
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Andrew Quinn
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Laura A Martello
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Shivakumar Vignesh
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
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29
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Duijster JW, Franz E, Neefjes J, Mughini-Gras L. Bacterial and Parasitic Pathogens as Risk Factors for Cancers in the Gastrointestinal Tract: A Review of Current Epidemiological Knowledge. Front Microbiol 2021; 12:790256. [PMID: 34956157 PMCID: PMC8692736 DOI: 10.3389/fmicb.2021.790256] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships.
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Affiliation(s)
- Janneke W. Duijster
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Eelco Franz
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Jacques Neefjes
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Lapo Mughini-Gras
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
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30
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The gastrointestinal microbiota in colorectal cancer cell migration and invasion. Clin Exp Metastasis 2021; 38:495-510. [PMID: 34748126 DOI: 10.1007/s10585-021-10130-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023]
Abstract
Colorectal carcinoma is the third most common cancer in developed countries and the second leading cause of cancer-related mortality. Interest in the influence of the intestinal microbiota on CRC emerged rapidly in the past few years, and the close presence of microbiota to the tumour mass creates a unique microenvironment in CRC. The gastrointestinal microbiota secrete factors that can contribute to CRC metastasis by influencing, for example, epithelial-to-mesenchymal transition. Although the role of EMT in metastasis is well-studied, mechanisms by which gastrointestinal microbiota contribute to the progression of CRC remain poorly understood. In this review, we will explore bacterial factors that contribute to the migration and invasion of colorectal carcinoma and the mechanisms involved. Bacteria involved in the induction of metastasis in primary CRC include Fusobacterium nucleatum, Enterococcus faecalis, enterotoxigenic Bacteroides fragilis, Escherichia coli and Salmonella enterica. Examples of prominent bacterial factors secreted by these bacteria include Fusobacterium adhesin A and Bacteroides fragilis Toxin. Most of these factors induce EMT-like properties in carcinoma cells and, as such, contribute to disease progression by affecting cell-cell adhesion, breakdown of the extracellular matrix and reorganisation of the cytoskeleton. It is of utmost importance to elucidate how bacterial factors promote CRC recurrence and metastasis to increase patient survival. So far, mainly animal models have been used to demonstrate this interplay between the host and microbiota. More human-based models are needed to study the mechanisms that promote migration and invasion and mimic the progression and recurrence of CRC.
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31
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Dalal N, Jalandra R, Bayal N, Yadav AK, Harshulika, Sharma M, Makharia GK, Kumar P, Singh R, Solanki PR, Kumar A. Gut microbiota-derived metabolites in CRC progression and causation. J Cancer Res Clin Oncol 2021; 147:3141-3155. [PMID: 34273006 DOI: 10.1007/s00432-021-03729-w] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/04/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities. PURPOSE In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development. CONCLUSION Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy.
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Affiliation(s)
- Nishu Dalal
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India
- Department of Environmental Science, Satyawati College, Delhi University, Delhi, 110052, India
| | - Rekha Jalandra
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India
- Department of Zoology, Maharshi Dayanand University, Rohtak, 124001, India
| | - Nitin Bayal
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India
| | - Amit K Yadav
- Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Harshulika
- Ministry of Environment, Forest and Climate Change, New Delhi, 110003, India
| | - Minakshi Sharma
- Department of Zoology, Maharshi Dayanand University, Rohtak, 124001, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, 110029, India
| | - Pramod Kumar
- Sri Aurobindo College, Delhi University, New Delhi, 110067, India
| | - Rajeev Singh
- Department of Environmental Science, Satyawati College, Delhi University, Delhi, 110052, India
| | - Pratima R Solanki
- Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi, 110067, India.
| | - Anil Kumar
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India.
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Sayed IM, Ramadan HKA, El-Mokhtar MA, Abdel-Wahid L. Microbiome and gastrointestinal malignancies. CURRENT OPINION IN PHYSIOLOGY 2021. [DOI: 10.1016/j.cophys.2021.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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33
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Shariati A, Razavi S, Ghaznavi-Rad E, Jahanbin B, Akbari A, Norzaee S, Darban-Sarokhalil D. Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study. Infect Agent Cancer 2021; 16:41. [PMID: 34108031 PMCID: PMC8191199 DOI: 10.1186/s13027-021-00381-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 05/31/2021] [Indexed: 12/02/2022] Open
Abstract
Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.
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Affiliation(s)
- Aref Shariati
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ehsanollah Ghaznavi-Rad
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Arak University of Medical Sciences, Arak, Iran
| | - Behnaz Jahanbin
- Department of Pathology, Cancer Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran
| | - Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Samira Norzaee
- Research Center for Environmental Health Technology, Iran University of Medical Sciences, Tehran, Iran
| | - Davood Darban-Sarokhalil
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. .,Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Fathi M, Pustokhina I, Kuznetsov SV, Khayrullin M, Hojjat-Farsangi M, Karpisheh V, Jalili A, Jadidi-Niaragh F. T-cell immunoglobulin and ITIM domain, as a potential immune checkpoint target for immunotherapy of colorectal cancer. IUBMB Life 2021; 73:726-738. [PMID: 33686787 DOI: 10.1002/iub.2461] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/31/2021] [Accepted: 03/02/2021] [Indexed: 12/24/2022]
Abstract
The importance of the tumor microenvironment in cancer progression has been well studied for many years. Immune checkpoint inhibitors (ICIs) are regarded as potential strategies in enhancing the immune responses in patients with cancer, particularly colorectal cancer (CRC). Notably, CRCs are extraordinarily heterogeneous and mostly are microsatellite-stable (MSS) or cold tumors, which means that the immune response is not usually as strong as that of foreign cells. T-cell immunoglobulin and ITIM domain (TIGIT) is a new immune checkpoint receptor overexpressed inside the CRC tumor-immune microenvironments. Moreover, several studies have shown that TIGIT in combination with other ICIs and/or conventional treatments, can lead to a robust anti-tumor response in CRC. This review looks deep inside TIGIT expression patterns, their various functions, and possible immunotherapy strategies to increase survival rates and decrease immune-related adverse events.
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Affiliation(s)
- Mehrdad Fathi
- Cancer and Immunology Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | | | - Sergey V Kuznetsov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Mars Khayrullin
- Department of Research Management, K.G. Razumovsky Moscow State, University of Technologies and Management (The First Cossack University), Moscow, Russian Federation
| | | | - Vahid Karpisheh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Jalili
- Cancer and Immunology Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Farhad Jadidi-Niaragh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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35
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Loke YL, Chew MT, Ngeow YF, Lim WWD, Peh SC. Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota. Front Cell Infect Microbiol 2020; 10:603086. [PMID: 33364203 PMCID: PMC7753026 DOI: 10.3389/fcimb.2020.603086] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.
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Affiliation(s)
- Yean Leng Loke
- Centre for Biomedical Physics, School of Healthcare and Medical Sciences, Sunway University, Petaling Jaya, Malaysia
| | - Ming Tsuey Chew
- Centre for Biomedical Physics, School of Healthcare and Medical Sciences, Sunway University, Petaling Jaya, Malaysia
| | - Yun Fong Ngeow
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Malaysia.,Centre for Research on Communicable Diseases, Universiti Tunku Abdul Rahman, Kajang, Malaysia
| | - Wendy Wan Dee Lim
- Department of Gastroenterology, Sunway Medical Centre, Petaling Jaya, Malaysia
| | - Suat Cheng Peh
- Ageing Health and Well-Being Research Centre, Sunway University, Petaling Jaya, Malaysia.,Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, Petaling Jaya, Malaysia
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36
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Keane JM, Joyce SA, Gahan CGM, Hyland NP, Houston A. Microbial Metabolites as Molecular Mediators of Host-Microbe Symbiosis in Colorectal Cancer. Results Probl Cell Differ 2020; 69:581-603. [PMID: 33263888 DOI: 10.1007/978-3-030-51849-3_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Abstract
The symbiosis between the gut microbiota and the host has been identified as an integral part of normal human physiology and physiological development. Research in germ-free or gnotobiotic animals has demonstrated the importance of this symbiosis in immune, vascular, hepatic, respiratory and metabolic systems. Disruption of the microbiota can also contribute to disease, and the microbiota has been implicated in numerous intestinal and extra-intestinal pathologies including colorectal cancer. Interactions between host and microbiota can occur either directly or indirectly, via microbial-derived metabolites. In this chapter, we focus on two major products of microbial metabolism, short-chain fatty acids and bile acids, and their role in colorectal cancer. Short-chain fatty acids are the products of microbial fermentation of complex carbohydrates and confer protection against cancer risk, while bile acids are compounds which are endogenous to the host, but undergo microbial modification in the large intestine leading to alterations in their bioactivity. Lastly, we discuss the ability of microbial modulation to mediate cancer risk and the potential to harness this ability as a prophylactic or therapeutic treatment in colorectal cancer.
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Affiliation(s)
- J M Keane
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
| | - S A Joyce
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
| | - C G M Gahan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- School of Pharmacy, University College Cork, Cork, Ireland
| | - N P Hyland
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Physiology, University College Cork, Cork, Ireland.
| | - A Houston
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
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37
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Koliarakis I, Athanasakis E, Sgantzos M, Mariolis-Sapsakos T, Xynos E, Chrysos E, Souglakos J, Tsiaoussis J. Intestinal Microbiota in Colorectal Cancer Surgery. Cancers (Basel) 2020; 12:E3011. [PMID: 33081401 PMCID: PMC7602998 DOI: 10.3390/cancers12103011] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/04/2020] [Accepted: 10/13/2020] [Indexed: 02/07/2023] Open
Abstract
The intestinal microbiota consists of numerous microbial species that collectively interact with the host, playing a crucial role in health and disease. Colorectal cancer is well-known to be related to dysbiotic alterations in intestinal microbiota. It is evident that the microbiota is significantly affected by colorectal surgery in combination with the various perioperative interventions, mainly mechanical bowel preparation and antibiotic prophylaxis. The altered postoperative composition of intestinal microbiota could lead to an enhanced virulence, proliferation of pathogens, and diminishment of beneficial microorganisms resulting in severe complications including anastomotic leakage and surgical site infections. Moreover, the intestinal microbiota could be utilized as a possible biomarker in predicting long-term outcomes after surgical CRC treatment. Understanding the underlying mechanisms of these interactions will further support the establishment of genomic mapping of intestinal microbiota in the management of patients undergoing CRC surgery.
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Affiliation(s)
- Ioannis Koliarakis
- Laboratory of Anatomy, School of Medicine, University of Crete, 70013 Heraklion, Greece;
| | - Elias Athanasakis
- Department of General Surgery, University Hospital of Heraklion, 71110 Heraklion, Greece; (E.A.); (E.C.)
| | - Markos Sgantzos
- Laboratory of Anatomy, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece;
| | - Theodoros Mariolis-Sapsakos
- Surgical Department, National and Kapodistrian University of Athens, Agioi Anargyroi General and Oncologic Hospital of Kifisia, 14564 Athens, Greece;
| | - Evangelos Xynos
- Department of Surgery, Creta Interclinic Hospital of Heraklion, 71305 Heraklion, Greece;
| | - Emmanuel Chrysos
- Department of General Surgery, University Hospital of Heraklion, 71110 Heraklion, Greece; (E.A.); (E.C.)
| | - John Souglakos
- Laboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, Greece;
| | - John Tsiaoussis
- Laboratory of Anatomy, School of Medicine, University of Crete, 70013 Heraklion, Greece;
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Pop OL, Vodnar DC, Diaconeasa Z, Istrati M, Bințințan A, Bințințan VV, Suharoschi R, Gabbianelli R. An Overview of Gut Microbiota and Colon Diseases with a Focus on Adenomatous Colon Polyps. Int J Mol Sci 2020; 21:7359. [PMID: 33028024 PMCID: PMC7582333 DOI: 10.3390/ijms21197359] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 09/30/2020] [Accepted: 10/02/2020] [Indexed: 12/24/2022] Open
Abstract
It is known and accepted that the gut microbiota composition of an organism has an impact on its health. Many studies deal with this topic, the majority discussing gastrointestinal health. Adenomatous colon polyps have a high prevalence as colon cancer precursors, but in many cases, they are hard to diagnose in their early stages. Gut microbiota composition correlated with the presence of adenomatous colon polyps may be a noninvasive and efficient tool for diagnosis with a high impact on human wellbeing and favorable health care costs. This review is meant to analyze the gut microbiota correlated with the presence of adenomatous colon polyps as the first step for early diagnosis, prophylaxis, and treatment.
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Affiliation(s)
- Oana Lelia Pop
- Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (O.L.P.); (D.C.V.); (Z.D.)
| | - Dan Cristian Vodnar
- Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (O.L.P.); (D.C.V.); (Z.D.)
| | - Zorita Diaconeasa
- Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (O.L.P.); (D.C.V.); (Z.D.)
| | - Magdalena Istrati
- Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400158 Cluj-Napoca, Romania;
| | - Adriana Bințințan
- 1st Medical Clinic, Department of Gastroenterology, Emergency County Hospital, 400006 Cluj Napoca, Romania;
| | - Vasile Virgil Bințințan
- 1st Surgical Clinic, Department of Surgery, University of Medicine and Pharmacy Cluj Napoca, 400006 Cluj Napoca, Romania;
| | - Ramona Suharoschi
- Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania; (O.L.P.); (D.C.V.); (Z.D.)
| | - Rosita Gabbianelli
- Unit of Molecular Biology, School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy
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Chen Y, Yang Y, Gu J. Clinical Implications of the Associations Between Intestinal Microbiome and Colorectal Cancer Progression. Cancer Manag Res 2020; 12:4117-4128. [PMID: 32606919 PMCID: PMC7295108 DOI: 10.2147/cmar.s240108] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 04/03/2020] [Indexed: 12/24/2022] Open
Abstract
Intestinal microbiome influences host immunity and several diseases, including cancer, in their areas of colonization. Microbial dysbiosis and over-colonization of specific microbes within the colorectal mucosa can impact the progress of carcinogenesis. Investigations initially focused on the mechanisms by which the intestinal microbiome initiates or promotes the development of colorectal cancer, including DNA damage, induction of chromosomal instability, and regulation of host immune responses. Some studies on the clinicopathological features have reported that specific strains present at high abundance are associated with advanced stage and positive lymph nodes in colorectal cancer. In this context, we reviewed the relationship between the intestinal microbiome and the clinical features (patient age, disease staging, prognosis, etc.) of patients with colorectal cancer, and evaluated the potential pathogenesis caused by the intestinal microbiome in disease progress. This article assessed whether changes in distinct species or strains occur during the period of cancer advancement. Overall, age grouping does not bring about significant differences in the constitution of microbiome. The disease stages show their distinct distribution in some species and strains. Oncogenic species are generally enriched in patients with poor prognosis, including low infiltration of CD3+ T cells, poor differentiation, widespread invasion, high microsatellite instability, CpG island methylator phenotype, BRAF mutation, short overall survival, and disease-free survival. The implications of those changes we discussed may assist in comprehensive understanding of the tumorigenesis of colorectal cancer from a microbiological perspective, finding potential biomarkers for colorectal cancer.
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Affiliation(s)
- Yongkang Chen
- Department of Gastrointestinal Surgery III, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China
| | - Yong Yang
- Department of Gastrointestinal Surgery III, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China
| | - Jin Gu
- Department of Gastrointestinal Surgery III, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China.,Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing 100144, People's Republic of China.,Peking-Tsinghua Center for Life Science, Tsinghua University, Beijing 100142, People's Republic of China
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Valguarnera E, Wardenburg JB. Good Gone Bad: One Toxin Away From Disease for Bacteroides fragilis. J Mol Biol 2019; 432:765-785. [PMID: 31857085 DOI: 10.1016/j.jmb.2019.12.003] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 11/27/2019] [Accepted: 12/05/2019] [Indexed: 02/06/2023]
Abstract
The human gut is colonized by hundreds of trillions of microorganisms whose acquisition begins during early infancy. Species from the Bacteroides genus are ubiquitous commensals, comprising about thirty percent of the human gut microbiota. Bacteroides fragilis is one of the least abundant Bacteroides species, yet is the most common anaerobe isolated from extraintestinal infections in humans. A subset of B. fragilis strains carry a genetic element that encodes a metalloprotease enterotoxin named Bacteroides fragilis toxin, or BFT. Toxin-bearing strains, or Enterotoxigenic B. fragilis (ETBF) cause acute and chronic intestinal disease in children and adults. Despite this association with disease, around twenty percent of the human population appear to be asymptomatic carriers of ETBF. BFT damages the colonic epithelial barrier by inducing cleavage of the zonula adherens protein E-cadherin and initiating a cell signaling response characterized by inflammation and c-Myc-dependent pro-oncogenic hyperproliferation. As a consequence, mice harboring genetic mutations that predispose to colonic inflammation or tumor formation are uniquely susceptible to toxin-mediated injury. The recent observation of ETBF-bearing biofilms in colon biopsies from humans with colon cancer susceptibility loci strongly suggests that ETBF is a driver of colorectal cancer. This article will address ETBF biology from a host-pathobiont perspective, including clinical data, analysis of molecular mechanisms of disease, and the complex ecological context of the human gut.
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Affiliation(s)
- Ezequiel Valguarnera
- Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Ave. Box 8208, St. Louis, MO 63110
| | - Juliane Bubeck Wardenburg
- Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Ave. Box 8208, St. Louis, MO 63110.
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41
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Risks associated with enterococci as probiotics. Food Res Int 2019; 129:108788. [PMID: 32036912 DOI: 10.1016/j.foodres.2019.108788] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 10/07/2019] [Accepted: 10/29/2019] [Indexed: 01/01/2023]
Abstract
Probiotics are naturally occurring microorganisms that confer health benefits by altering host commensal microbiota, modulating immunity, enhancing intestinal barrier function, or altering pain perception. Enterococci are human and animal intestinal commensals that are used as probiotics and in food production. These microorganisms, however, express many virulence traits including cytolysin, proteases, aggregation substance, capsular polysaccharide, enterococcal surface protein, biofilm formation, extracellular superoxide, intestinal translocation, and resistance to innate immunity that can lead to serious hospital-acquired infections. In addition, enterococci are facile in acquiring antibiotic resistance genes to many clinically important antibiotics encoded on a wide variety of conjugative plasmids, transposons, and bacteriophages. The pathogenicity and disease burden caused by enterococci render them poor choices as probiotics. No large, randomized, placebo-controlled clinical trials have demonstrated the safety and efficacy of any enterococcal probiotic. As a result, no enterococcal probiotic has been approved by the United States Food and Drug Administration for the treatment, cure, or amelioration of human disease. In 2007, the European Food Safety Authority concluded that enterococci do not meet the standard for "Qualified Presumption of Safety". Enterococcal strains used or proposed for use as probiotics should be carefully screened for efficacy and safety.
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Tarashi S, Siadat SD, Ahmadi Badi S, Zali M, Biassoni R, Ponzoni M, Moshiri A. Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer? Microorganisms 2019; 7:E561. [PMID: 31766208 PMCID: PMC6920974 DOI: 10.3390/microorganisms7110561] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/22/2019] [Accepted: 09/04/2019] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.
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Affiliation(s)
- Samira Tarashi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Sara Ahmadi Badi
- Microbiology Research Center, Pasteur Institute of Iran, 1316943551 Tehran, Iran; (S.T.); (S.D.S.); (S.A.B.)
- Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, 1316943551 Tehran, Iran
| | - Mohammadreza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
| | - Roberto Biassoni
- Laboratory of Molecular Medicine, IRCCS Instituto Giannina Gaslini, 16147 Genova, Italy;
| | - Mirco Ponzoni
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
| | - Arfa Moshiri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran;
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
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Targeting Programmed Fusobacterium nucleatum Fap2 for Colorectal Cancer Therapy. Cancers (Basel) 2019; 11:cancers11101592. [PMID: 31635333 PMCID: PMC6827134 DOI: 10.3390/cancers11101592] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 10/13/2019] [Accepted: 10/14/2019] [Indexed: 12/18/2022] Open
Abstract
Colorectal patients generally have the maximum counts of Fusobacterium nucleatum (F. nucleatum) in tumors and elevate colorectal adenomas and carcinomas, which show the lowest rate of human survival. Hence, F. nucleatum is a diagnostic marker of colorectal cancer (CRC). Studies demonstrated that targeting fusobacterial Fap2 or polysaccharide of the host epithelium may decrease fusobacteria count in the CRC. Attenuated F. nucleatum-Fap2 prevents transmembrane signals and inhibits tumorigenesis inducing mechanisms. Hence, in this review, we hypothesized that application of genetically programmed fusobacterium can be skillful and thus reduce fusobacterium in the CRC. Genetically programmed F. nucleatum is a promising antitumor strategy.
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Dai Z, Zhang J, Wu Q, Chen J, Liu J, Wang L, Chen C, Xu J, Zhang H, Shi C, Li Z, Fang H, Lin C, Tang D, Wang D. The role of microbiota in the development of colorectal cancer. Int J Cancer 2019; 145:2032-2041. [PMID: 30474116 PMCID: PMC6899977 DOI: 10.1002/ijc.32017] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 10/25/2018] [Accepted: 11/13/2018] [Indexed: 02/05/2023]
Abstract
Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.
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Affiliation(s)
- Zhujiang Dai
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Jingqiu Zhang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Qi Wu
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Juan Chen
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Jun Liu
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Lu Wang
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Chaowu Chen
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Jiaming Xu
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Hongpeng Zhang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Chunfeng Shi
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Zhen Li
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Huiwen Fang
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Chaobiao Lin
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Dong Tang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Daorong Wang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
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45
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Reis SAD, da Conceição LL, Peluzio MDCG. Intestinal microbiota and colorectal cancer: changes in the intestinal microenvironment and their relation to the disease. J Med Microbiol 2019; 68:1391-1407. [PMID: 31424382 DOI: 10.1099/jmm.0.001049] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Tools that predict the risk of colorectal cancer are important for early diagnosis, given the high mortality rate for this cancer. The composition of the intestinal microbiota is now considered to be a risk factor for the development of colorectal cancer. This discovery has motivated a growing number of studies to identify the micro-organisms responsible for the onset and/or progression of colorectal cancer. With this in mind, this review discusses the relationship between the composition of the intestinal microbiota and colorectal cancer risk. Prospective and case-control studies indicate that the intestinal microbiota of individuals with colorectal cancer usually contains a greater proportion of bacteria responsible for gastrointestinal tract inflammatory diseases, as well as bacteria that produce toxins and carcinogenic metabolites. In contrast, there tends to be a reduced presence of butyric acid-producing bacteria, probiotic bacteria and potentially probiotic bacteria. Despite these differences, the onset and development of colorectal cancer cannot be attributed to a specific micro-organism. Thus, studies focused on the formation of the intestinal microbiota and factors that modulate its composition are important for the development of approaches for colorectal cancer prevention.
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Affiliation(s)
- Sandra Aparecida Dos Reis
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil
| | - Lisiane Lopes da Conceição
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil
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46
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Zhou Y, Xu H, Huang H, Li Y, Chen H, He J, Du Y, Chen Y, Zhou Y, Nie Y. Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders? BIOMED RESEARCH INTERNATIONAL 2019; 2019:3469754. [PMID: 31467881 PMCID: PMC6699279 DOI: 10.1155/2019/3469754] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 06/04/2019] [Accepted: 06/17/2019] [Indexed: 02/07/2023]
Abstract
Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.
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Affiliation(s)
- Youlian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Haoming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Hongli Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Yingfei Li
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Huiting Chen
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Jie He
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Yanlei Du
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Ye Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yongjian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Yuqiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
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Enterococcus faecalis Gluconate Phosphotransferase System Accelerates Experimental Colitis and Bacterial Killing by Macrophages. Infect Immun 2019; 87:IAI.00080-19. [PMID: 31036600 DOI: 10.1128/iai.00080-19] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 04/21/2019] [Indexed: 02/07/2023] Open
Abstract
Enterococcus faecalis strains are resident intestinal bacteria associated with invasive infections, inflammatory bowel diseases, and colon cancer. Although factors promoting E. faecalis colonization of intestines are not fully known, one implicated pathway is a phosphotransferase system (PTS) in E. faecalis strain OG1RF that phosphorylates gluconate and contains the genes OG1RF_12399 to OG1RF_12402 (OG1RF_12399-12402). We hypothesize that this PTS permits growth in gluconate, facilitates E. faecalis intestinal colonization, and exacerbates colitis. We generated E. faecalis strains containing deletions/point mutations in this PTS and measured bacterial growth and PTS gene expression in minimal medium supplemented with selected carbohydrates. We show that E. faecalis upregulates OG1RF_12399 transcription specifically in the presence of gluconate and that E. faecalis strains lacking, or harboring a single point mutation in, OG1RF_12399-12402 are unable to grow in minimal medium containing gluconate. We colonized germfree wild-type and colitis-prone interleukin-10-deficient mice with defined bacterial consortia containing the E. faecalis strains and measured inflammation and bacterial abundance in the colon. We infected macrophage and intestinal epithelial cell lines with the E. faecalis strains and measured intracellular bacterial survival and proinflammatory cytokine secretion. The presence of OG1RF_12399-12402 is not required for E. faecalis colonization of the mouse intestine but is associated with an accelerated onset of experimental colitis in interleukin-10-deficient mice, altered bacterial composition in the colon, enhanced E. faecalis survival within macrophages, and increased proinflammatory cytokine secretion by colon tissue and macrophages. Further studies of bacterial carbohydrate metabolism in general, and E. faecalis PTS-gluconate in particular, during inflammation may identify new mechanisms of disease pathogenesis.
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48
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Saus E, Iraola-Guzmán S, Willis JR, Brunet-Vega A, Gabaldón T. Microbiome and colorectal cancer: Roles in carcinogenesis and clinical potential. Mol Aspects Med 2019; 69:93-106. [PMID: 31082399 PMCID: PMC6856719 DOI: 10.1016/j.mam.2019.05.001] [Citation(s) in RCA: 227] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/08/2019] [Indexed: 02/08/2023]
Abstract
The gastrointestinal tract harbors most of the microbiota associated with humans. In recent years, there has been a surge of interest in assessing the relationships between the gut microbiota and several gut alterations, including colorectal cancer. Changes in the gut microbiota in patients suffering colorectal cancer suggest a possible role of host-microbe interactions in the origin and development of this malignancy and, at the same time, open the door for novel ways of preventing, diagnosing, or treating this disease. In this review we survey current knowledge on the healthy microbiome of the gut and how it is altered in colorectal cancer and other related disease conditions. In describing past studies we will critically assess technical limitations of different approaches and point to existing challenges in microbiome research. We will have a special focus on host-microbiome interaction mechanisms that may be important to explain how dysbiosis can lead to chronic inflammation and drive processes that influence carcinogenesis and tumor progression in colon cancer. Finally, we will discuss the potential of recent developments of novel microbiota-based therapeutics and diagnostic tools for colorectal cancer.
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Affiliation(s)
- Ester Saus
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Susana Iraola-Guzmán
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Jesse R Willis
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain.
| | - Anna Brunet-Vega
- Oncology Service, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain.
| | - Toni Gabaldón
- Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain; Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain; ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain.
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49
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De Almeida CV, Lulli M, di Pilato V, Schiavone N, Russo E, Nannini G, Baldi S, Borrelli R, Bartolucci G, Menicatti M, Taddei A, Ringressi MN, Niccolai E, Prisco D, Rossolini GM, Amedei A. Differential Responses of Colorectal Cancer Cell Lines to Enterococcus faecalis' Strains Isolated from Healthy Donors and Colorectal Cancer Patients. J Clin Med 2019; 8:388. [PMID: 30897751 PMCID: PMC6463247 DOI: 10.3390/jcm8030388] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 03/12/2019] [Accepted: 03/15/2019] [Indexed: 02/06/2023] Open
Abstract
The metabolites produced by the host's gut microbiota have an important role in the maintenance of intestinal homeostasis, but can also act as toxins and induce DNA damage in colorectal epithelial cells increasing the colorectal cancer (CRC) chance. In this scenario, the impact of some of the components of the natural human gastrointestinal microbiota, such as Enterococcus faecalis (E. faecalis), at the onset of CRC progression remains controversial. Since under dysbiotic conditions it could turn into a pathogen, the aim of this study was to compare the effect of E. faecalis' strains (isolated from CRC patients and healthy subjects' stools) on the proliferation of different colorectal cells lines. First, we isolated and genotyping characterized the Enterococcus faecalis' strains. Then, we analyzed the proliferation index (by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) of three tumor and one normal intestinal cell lines, previously exposed to E. faecalis strains pre-cultured medium. Stool samples of CRC patients demonstrated a reduced frequency of E. faecalis compared to healthy subjects. In addition, the secreted metabolites of E. faecalis' strains, isolated from healthy donors, decreased the human ileocecal adenocarcinoma cell line HCT-8 and human colon carcinoma cell line HCT-116 cell proliferation without effects on human colorectal adenocarcinoma cell line SW620 and on normal human diploid cell line CLR-1790. Notably, the metabolites of the strains isolated from CRC patients did not influence the cell growth of CRC cell lines. Our results demonstrated a new point of view in the investigation of E. faecalis' role in CRC development, which raises awareness of the importance of not only associating the presence/absence of a unique microorganism, but also in defining the specific characteristics of the different investigated strains.
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Affiliation(s)
| | - Matteo Lulli
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
| | - Vincenzo di Pilato
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Nicola Schiavone
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Giulia Nannini
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Simone Baldi
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Rossella Borrelli
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Gianluca Bartolucci
- Department of Neurosciences, Psychology, Drug Research and Child Health Section of Pharmaceutical and Nutraceutical Sciences University of Florence, 50139 Florence, Italy.
| | - Marta Menicatti
- Department of Neurosciences, Psychology, Drug Research and Child Health Section of Pharmaceutical and Nutraceutical Sciences University of Florence, 50139 Florence, Italy.
| | - Antonio Taddei
- Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
| | - Maria Novella Ringressi
- Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
| | - Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Domenico Prisco
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
| | - Gian Maria Rossolini
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
- Department of Microbiology and Virology Unit, Florence Careggi University Hospital, 50134 Florence, Italy.
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
- Department of Biomedicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134 Florence, Italy.
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Wu Y, Shi L, Li Q, Wu J, Peng W, Li H, Chen K, Ren Y, Fu X. Microbiota Diversity in Human Colorectal Cancer Tissues Is Associated with Clinicopathological Features. Nutr Cancer 2019; 71:214-222. [PMID: 30843732 DOI: 10.1080/01635581.2019.1578394] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Yaxin Wu
- Department of Gastroenterology, Central Hospital of Dazhou City, Sichuan, China
| | - Lei Shi
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Qing Li
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Jiao Wu
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Wei Peng
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Huan Li
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Kequan Chen
- Department of Gastroenterology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yixing Ren
- Department of Gastrointestinal surgery, the Affiliated Hospital of North Sichuan Medical College, Sichuan, China
| | - Xiangsheng Fu
- Department of Gastroenterology, the Affiliated Hospital of North Sichuan Medical College, Sichuan, China
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