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Su Y, Fan X, Cai X, Ning J, Shen M. Effects of fecal microbiota transplantation combined with selenium on intestinal microbiota in mice with colorectal cancer. Biochem Biophys Res Commun 2024; 733:150580. [PMID: 39213702 DOI: 10.1016/j.bbrc.2024.150580] [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: 06/02/2024] [Revised: 08/01/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024]
Abstract
Colorectal cancer (CRC) is the third most common cancer in the world. With the development of high-throughput gene sequencing technology, homeostasis imbalance of the intestinal microbiota has been proven to play a key role in the pathogenesis of CRC. Furthermore, fecal bacteria transplantation (FMT) has been shown to alter the intestinal microecology, and is potentially an effective treatment for CRC. Sodium selenite plays an important role in anticancer adjuvant therapy due to its high pro-oxidation characteristics. In this study, a murine CRC tumor model was induced by AOM/DSS, and CRC mice were treated by FMT, sodium selenite, and FMT combined with sodium selenite. The results showed that FMT, sodium selenite, and FMT combined with sodium selenite inhibited the occurrence of CRC in mice, increased the abundance of beneficial intestinal bacteria, produced different microorganisms, and changed the metabolic pathways of the intestinal microbiota. In summary, FMT, sodium selenite, and FMT combined with sodium selenite can inhibit the occurrence of CRC by increasing the abundance of beneficial bacteria and regulating phenotypes and metabolic pathways. Notably, the effect of FMT combined with sodium selenite in reducing the number of tumors, protecting intestinal tissues, and restoring the diversity and richness of the intestinal microbiota is superior to that of FMT alone or sodium selenite alone. The results of this study provide new ideas for the application of FMT and selenium in the treatment of CRC.
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Affiliation(s)
- Yintong Su
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Xingxing Fan
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Xiaohua Cai
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Jiayu Ning
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Mei Shen
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
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2
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Baas FS, Brusselaers N, Nagtegaal ID, Engstrand L, Boleij A. Navigating beyond associations: Opportunities to establish causal relationships between the gut microbiome and colorectal carcinogenesis. Cell Host Microbe 2024; 32:1235-1247. [PMID: 39146796 DOI: 10.1016/j.chom.2024.07.008] [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: 05/15/2024] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 08/17/2024]
Abstract
The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs.
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Affiliation(s)
- Floor S Baas
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Nele Brusselaers
- Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden; Global Health Institute, University of Antwerp, Antwerp, Belgium
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Lars Engstrand
- Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
| | - Annemarie Boleij
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
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3
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Su Y, Cai X, Fan X, Ning J, Shen M. Effect of Trace Element Selenium on the Intestinal Microbial Community in Nude Mice with Colorectal Cancer. Microorganisms 2024; 12:1336. [PMID: 39065104 PMCID: PMC11279152 DOI: 10.3390/microorganisms12071336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/31/2024] [Accepted: 06/18/2024] [Indexed: 07/28/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. The role of intestinal microbiota in carcinogenesis has also become an important research topic, and CRC is closely related to the intestinal microbiota. Selenium-containing compounds have attracted more attention as anticancer drugs as they can have minimal side effects. The purpose of this study was to determine and compare the effect of sodium selenite and selenomethionine on the microbial communities of nude mice with CRC. A CRC ectopic tumorigenesis model was established by subcutaneously injecting HCT116 cells into nude mice. The mice were then intraperitoneally injected with sodium selenite and selenomethionine for 24 days to regulate their intestinal microbiota. Compared with sodium selenite, selenomethionine resulted in a greater reduction in the richness and diversity of intestinal microbiota in nude mice with CRC, and the richness and diversity were closer to healthy levels. Selenomethionine also regulated a wider variety of flora. Additionally, sodium selenite and selenomethionine produced different microorganisms, changed function and metabolic pathways in the intestinal microbiota. Both sodium selenite and selenomethionine have certain effects on restoring the intestinal microbial diversity in nude mice with CRC, and the effect of selenomethionine is better than that of sodium selenite.
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Affiliation(s)
| | | | | | | | - Mei Shen
- Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; (Y.S.); (X.C.); (X.F.); (J.N.)
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Rifkin SB, Sze MA, Tuck K, Koeppe E, Stoffel EM, Schloss PD. Gut Microbiome Composition in Lynch Syndrome With and Without History of Colorectal Neoplasia and Non-Lynch Controls. J Gastrointest Cancer 2024; 55:207-218. [PMID: 37310549 DOI: 10.1007/s12029-023-00925-4] [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] [Accepted: 02/24/2023] [Indexed: 06/14/2023]
Abstract
BACKGROUND While Lynch syndrome (LS) is a highly penetrant colorectal cancer (CRC) syndrome, there is considerable variation in penetrance; few studies have investigated the association between microbiome and CRC risk in LS. We analyzed the microbiome composition among individuals with LS with and without personal history of colorectal neoplasia (CRN) and non-LS controls. METHODS We sequenced the V4 region of the 16S rRNA gene from the stool of 46 individuals with LS and 53 individuals without LS. We characterized within community and in between community microbiome variation, compared taxon abundance, and built machine learning models to investigate the differences in microbiome. RESULTS There was no difference within or between community variations among LS groups, but there was a statistically significant difference in both within and between community variation comparing LS to non-LS. Streptococcus and Actinomyces were differentially enriched in LS-CRC compared to LS-without CRN. There were numerous differences in taxa abundance comparing LS to non-LS; notably, Veillonella was enriched and Faecalibacterium and Romboutsia were depleted in LS. Finally, machine learning models classifying LS from non-LS controls and LS-CRC from LS-without CRN performed moderately well. CONCLUSIONS Differences in microbiome composition between LS and non-LS may suggest a microbiome pattern unique to LS formed by underlying differences in epithelial biology and immunology. We found specific taxa differences among LS groups, which may be due to underlying anatomy. Larger prospective studies following for CRN diagnosis and microbiome composition changes are needed to determine if microbiome composition contributes to CRN development in patients with LS.
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Affiliation(s)
- S B Rifkin
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA.
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
| | - M A Sze
- Department of Immunology and Microbiology, University of Michigan, Ann Arbor, MI, 48109, USA
| | - K Tuck
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA
| | - E Koeppe
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - E M Stoffel
- Department of Internal Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA
| | - P D Schloss
- Department of Immunology and Microbiology, University of Michigan, Ann Arbor, MI, 48109, USA
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Xia Y. Statistical normalization methods in microbiome data with application to microbiome cancer research. Gut Microbes 2023; 15:2244139. [PMID: 37622724 PMCID: PMC10461514 DOI: 10.1080/19490976.2023.2244139] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 07/12/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
Mounting evidence has shown that gut microbiome is associated with various cancers, including gastrointestinal (GI) tract and non-GI tract cancers. But microbiome data have unique characteristics and pose major challenges when using standard statistical methods causing results to be invalid or misleading. Thus, to analyze microbiome data, it not only needs appropriate statistical methods, but also requires microbiome data to be normalized prior to statistical analysis. Here, we first describe the unique characteristics of microbiome data and the challenges in analyzing them (Section 2). Then, we provide an overall review on the available normalization methods of 16S rRNA and shotgun metagenomic data along with examples of their applications in microbiome cancer research (Section 3). In Section 4, we comprehensively investigate how the normalization methods of 16S rRNA and shotgun metagenomic data are evaluated. Finally, we summarize and conclude with remarks on statistical normalization methods (Section 5). Altogether, this review aims to provide a broad and comprehensive view and remarks on the promises and challenges of the statistical normalization methods in microbiome data with microbiome cancer research examples.
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Affiliation(s)
- Yinglin Xia
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois Chicago, Chicago, USA
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Chu Q, Wei W, Lao H, Li Y, Tan Y, Wei X, Huang B, Qin C, Tang Y. Machine learning algorithms for integrating clinical features to predict intracranial hemorrhage in patients with acute leukemia. Int J Neurosci 2023; 133:977-986. [PMID: 35156526 DOI: 10.1080/00207454.2022.2030327] [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: 04/10/2021] [Revised: 01/02/2022] [Accepted: 01/08/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND Intracranial hemorrhage (ICH) in acute leukemia (AL) patients leads to high morbidity and mortality, treatment approaches for ICH are generally ineffective. Thus, early identification of which subjects are at high risk of ICH is of key importance. Currently, machine learning can achieve well predictive capability through constructing algorithms that simultaneously exploit the information coming from clinical features. METHODS After rigid data preprocessing, 42 different clinical features from 948 AL patients were used to train different machine learning algorithms. We used the feature selection algorithms to select the top 10 features from 42 clinical features. To test the performance of the machine learning algorithms, we calculated area under the curve (AUC) values from receiver operating characteristic (ROC) curves along with 95% confidence intervals (CIs) by cross-validation. RESULTS With the 42 features, RF exhibited the best predictive power. After feature selection, the top 10 features were international normalized ratio (INR), prothrombin time (PT), creatinine (Cr), indirect bilirubin (IBIL), albumin (ALB), monocyte (MONO), platelet (PLT), lactic dehydrogenase (LDH), fibrinogen (FIB) and prealbumin (PA). Among the top 10 features, INR, PT, Cr, IBIL and ALB had high predictive performance with an AUC higher than 0.8 respectively. CONCLUSIONS The RF algorithm exhibited a higher cross-validated performance compared with the classical algorithms, and the selected important risk features should help in individualizing aggressive treatment in AL patients to prevent ICH. Efforts that will be made to test and optimize in independent samples will warrant the application of such algorithm and predictors in the future.
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Affiliation(s)
- Quanhong Chu
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Wenxin Wei
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Huan Lao
- Medical College of Guangxi University, Nanning, Guangxi, China
- School of Computer, Electronics and Information, Guangxi University, Nanning, Guangxi, China
| | - Yujian Li
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yafu Tan
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xiaoyong Wei
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Baozi Huang
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Chao Qin
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yanyan Tang
- Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Fu Y, Sun J, Wang Y, Li W. Glucose oxidase and metal catalysts combined tumor synergistic therapy: mechanism, advance and nanodelivery system. J Nanobiotechnology 2023; 21:400. [PMID: 37907972 PMCID: PMC10617118 DOI: 10.1186/s12951-023-02158-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/12/2023] [Indexed: 11/02/2023] Open
Abstract
Cancer has always posed a significant threat to human health, prompting extensive research into new treatment strategies due to the limitations of traditional therapies. Starvation therapy (ST) has garnered considerable attention by targeting the primary energy source, glucose, utilized by cancer cells for proliferation. Glucose oxidase (GOx), a catalyst facilitating glucose consumption, has emerged as a critical therapeutic agent for ST. However, mono ST alone struggles to completely suppress tumor growth, necessitating the development of synergistic therapy approaches. Metal catalysts possess enzyme-like functions and can serve as carriers, capable of combining with GOx to achieve diverse tumor treatments. However, ensuring enzyme activity preservation in normal tissue and activation specifically within tumors presents a crucial challenge. Nanodelivery systems offer the potential to enhance therapy effectiveness by improving the stability of therapeutic agents and enabling controlled release. This review primarily focuses on recent advances in the mechanism of GOx combined with metal catalysts for synergistic tumor therapy. Furthermore, it discusses various nanoparticles (NPs) constructs designed for synergistic therapy in different carrier categories. Finally, this review provides a summary of GOx-metal catalyst-based NPs (G-M) and offers insights into the challenges associated with G-M therapy, delivery design, and oxygen (O2) supply.
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Affiliation(s)
- Yuhan Fu
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
- Key Laboratory of Basic and Application Research of Beiyao Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
| | - Jialin Sun
- Postdoctoral Research Station, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
- Biological Science and Technology Department, Heilongjiang Minzu College, Harbin, Heilongjiang Province, China
| | - Yanhong Wang
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.
- Key Laboratory of Basic and Application Research of Beiyao Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.
| | - Weinan Li
- School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.
- Key Laboratory of Basic and Application Research of Beiyao Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.
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Li X, Feng J, Wang Z, Liu G, Wang F. Features of combined gut bacteria and fungi from a Chinese cohort of colorectal cancer, colorectal adenoma, and post-operative patients. Front Microbiol 2023; 14:1236583. [PMID: 37614602 PMCID: PMC10443710 DOI: 10.3389/fmicb.2023.1236583] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/20/2023] [Indexed: 08/25/2023] Open
Abstract
Colorectal cancer (CRC) accounts for the third highest morbidity burden among malignant tumors worldwide. Previous studies investigated gut microbiome changes that occur during colorectal adenomas (CRA) progression to overt CRC, thus highlighting the importance of the gut microbiome in carcinogenesis. However, few studies have examined gut microbiome characteristics across the entire spectrum, from CRC development to treatment. The study used 16S ribosomal ribonucleic acid and internal transcribed spacer amplicon sequencing to compare the composition of gut bacteria and fungi in a Chinese cohort of healthy controls (HC), CRC patients, CRA patients, and CRC postoperative patients (PP). Our analysis showed that beta diversity was significantly different among the four groups based on the gut bacterial and fungal data. A total of 51 species of bacteria and 8 species of fungi were identified in the HC, CRA, CRC, and PP groups. Correlation networks for both the gut bacteria and fungi in HC vs. CRA, HC vs. CRC, and HC vs. PP indicated some hub bacterial and fungal genera in each model, and the correlation between bacterial and fungal data indicated that a highly significant negative correlation exists among groups. Quantitative polymerase chain reaction (qPCR) analysis in a large cohort of HC, CRC, CRA, and PP patients demonstrated a significantly increasing trend of Fusobacterium nucleatum, Bifidobacterium bifidum, Candida albicans, and Saccharomyces cerevisiae in the feces of CRC patients than that of HC patients (p < 0.01). However, the abundance levels of CRA and PP were significantly lower in HC patients than those in CRC patients. Further studies are required to identify the functional consequences of the altered bacterial/fungal composition on metabolism and CRC tumorigenesis in the host.
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Affiliation(s)
- Xiaopeng Li
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Radiation Oncology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Jiahui Feng
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Zhanggui Wang
- Department of Radiation Oncology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Gang Liu
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Fan Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Chan FKL, Wong MCS, Chan AT, East JE, Chiu HM, Makharia GK, Weller D, Ooi CJ, Limsrivilai J, Saito Y, Hang DV, Emery JD, Makmun D, Wu K, Ali RAR, Ng SC. Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia. Gut 2023; 72:1240-1254. [PMID: 37019620 PMCID: PMC10314015 DOI: 10.1136/gutjnl-2023-329429] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/07/2023] [Indexed: 04/07/2023]
Abstract
Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.
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Affiliation(s)
- Francis K L Chan
- Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
| | - Martin C S Wong
- JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
- Centre for Health Education and Health Promotion, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - James E East
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Division of Gastroenterology and Hepatology, Mayo Clinic Healthcare, London, UK
| | - Han-Mo Chiu
- Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - David Weller
- Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
| | | | - Julajak Limsrivilai
- Internal Medicine, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Dao V Hang
- Hanoi Medical University, Hanoi, Vietnam
| | - Jon D Emery
- Department of General Practice, The University of Melbourne Faculty of Medicine Dentistry and Health Sciences, Melbourne, Victoria, Australia
| | | | - Kaichun Wu
- Xijing Hospital of Digestive Diseases, Xijing Hospital, Xian, China
| | | | - Siew C Ng
- Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
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Tsigalou C, Paraschaki A, Bragazzi NL, Aftzoglou K, Stavropoulou E, Tsakris Z, Vradelis S, Bezirtzoglou E. Alterations of gut microbiome following gastrointestinal surgical procedures and their potential complications. Front Cell Infect Microbiol 2023; 13:1191126. [PMID: 37333847 PMCID: PMC10272562 DOI: 10.3389/fcimb.2023.1191126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 05/23/2023] [Indexed: 06/20/2023] Open
Abstract
Intestinal microorganisms play a crucial role in shaping the host immunity and maintaining homeostasis. Nevertheless, alterations in gut bacterial composition may occur and these alterations have been linked with the pathogenesis of several diseases. In surgical practice, studies revealed that the microbiome of patients undergoing surgery changes and several post-operative complications seem to be associated with the gut microbiota composition. In this review, we aim to provide an overview of gut microbiota (GM) in surgical disease. We refer to several studies which describe alterations of GM in patients undergoing different types of surgery, we focus on the impacts of peri-operative interventions on GM and the role of GM in development of post-operative complications, such as anastomotic leak. The review aims to enhance comprehension regarding the correlation between GM and surgical procedures based in the current knowledge. However, preoperative and postoperative synthesis of GM needs to be further examined in future studies, so that GM-targeted measures could be assessed and the different surgery complications could be reduced.
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Affiliation(s)
- Christina Tsigalou
- Laboratory of Microbiology, Faculty of Medicine, Democritus University of Thrace, Dragana Campus, Alexandroupolis, Greece
| | - Afroditi Paraschaki
- Department of Biopathology/Microbiology, Faculty of Medicine, University General Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Nicola Luigi Bragazzi
- Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada
| | - K. Aftzoglou
- Medical School, Comenius University, Bratislava, Slovakia
| | - Elisavet Stavropoulou
- Department of Infectious Diseases, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon, Lausanne, Switzerland
| | - Z. Tsakris
- Laboratory of Microbiology, Department of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - S. Vradelis
- Department of Gastrenterology, Faculty of Medicine, Democritus University of Thrace, Dragana Campus, Alexandroupolis, Greece
| | - Eugenia Bezirtzoglou
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana, Alexandroupolis, Greece
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Wong CC, Yu J. Gut microbiota in colorectal cancer development and therapy. Nat Rev Clin Oncol 2023:10.1038/s41571-023-00766-x. [PMID: 37169888 DOI: 10.1038/s41571-023-00766-x] [Citation(s) in RCA: 225] [Impact Index Per Article: 112.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2023] [Indexed: 05/13/2023]
Abstract
Colorectal cancer (CRC) is one of the commonest cancers globally. A unique aspect of CRC is its intimate association with the gut microbiota, which forms an essential part of the tumour microenvironment. Research over the past decade has established that dysbiosis of gut bacteria, fungi, viruses and Archaea accompanies colorectal tumorigenesis, and these changes might be causative. Data from mechanistic studies demonstrate the ability of the gut microbiota to interact with the colonic epithelia and immune cells of the host via the release of a diverse range of metabolites, proteins and macromolecules that regulate CRC development. Preclinical and some clinical evidence also underscores the role of the gut microbiota in modifying the therapeutic responses of patients with CRC to chemotherapy and immunotherapy. Herein, we summarize our current understanding of the role of gut microbiota in CRC and outline the potential translational and clinical implications for CRC diagnosis, prevention and treatment. Emphasis is placed on how the gut microbiota could now be better harnessed by developing targeted microbial therapeutics as chemopreventive agents against colorectal tumorigenesis, as adjuvants for chemotherapy and immunotherapy to boost drug efficacy and safety, and as non-invasive biomarkers for CRC screening and patient stratification. Finally, we highlight the hurdles and potential solutions to translating our knowledge of the gut microbiota into clinical practice.
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Affiliation(s)
- Chi Chun Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
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12
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Tacconi E, Palma G, De Biase D, Luciano A, Barbieri M, de Nigris F, Bruzzese F. Microbiota Effect on Trimethylamine N-Oxide Production: From Cancer to Fitness-A Practical Preventing Recommendation and Therapies. Nutrients 2023; 15:563. [PMID: 36771270 PMCID: PMC9920414 DOI: 10.3390/nu15030563] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/11/2023] [Accepted: 01/13/2023] [Indexed: 01/24/2023] Open
Abstract
Trimethylamine N-oxide (TMAO) is a microbial metabolite derived from nutrients, such as choline, L-carnitine, ergothioneine and betaine. Recently, it has come under the spotlight for its close interactions with gut microbiota and implications for gastrointestinal cancers, cardiovascular disease, and systemic inflammation. The culprits in the origin of these pathologies may be food sources, in particular, high fat meat, offal, egg yolk, whole dairy products, and fatty fish, but intercalated between these food sources and the production of pro-inflammatory TMAO, the composition of gut microbiota plays an important role in modulating this process. The aim of this review is to explain how the gut microbiota interacts with the conversion of specific compounds into TMA and its oxidation to TMAO. We will first cover the correlation between TMAO and various pathologies such as dysbiosis, then focus on cardiovascular disease, with a particular emphasis on pro-atherogenic factors, and then on systemic inflammation and gastrointestinal cancers. Finally, we will discuss primary prevention and therapies that are or may become possible. Possible treatments include modulation of the gut microbiota species with diets, physical activity and supplements, and administration of drugs, such as metformin and aspirin.
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Affiliation(s)
- Edoardo Tacconi
- Department of Human Science and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy
| | - Giuseppe Palma
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy
| | - Davide De Biase
- Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy
| | - Antonio Luciano
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy
| | - Massimiliano Barbieri
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy
| | - Filomena de Nigris
- Department of Precision Medicine, School of Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Via De Crecchio 7, 80138 Naples, Italy
| | - Francesca Bruzzese
- S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy
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13
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Bosch S, Acharjee A, Quraishi MN, Rojas P, Bakkali A, Jansen EEW, Brizzio Brentar M, Kuijvenhoven J, Stokkers P, Struys E, Beggs AD, Gkoutos GV, de Meij TGJ, de Boer NKH. The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma. Gut Microbes 2022; 14:2038863. [PMID: 35188868 PMCID: PMC8865277 DOI: 10.1080/19490976.2022.2038863] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy (n = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities (n = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline (p = .001), ornithine (p = .02) and serine (p = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found (Bifidobacterium spp.↓, Anaerostipes spp.↓, Butyricimonas spp.↑, Faecalitalea spp.↑ and Catenibacterium spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, Faecalitalea spp. and Butyricimonas spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer.
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Affiliation(s)
- Sofie Bosch
- Amsterdam Umc, Vu University Medical Center, Department of Gastroenterology and Hepatology, Ag&m Research Institute, Amsterdam, The Netherlands,contact Sofie Bosch Amsterdam UMC, VU University Medical Center, De Boelelaan 11181081HZ, Amsterdam, The Netherlands
| | - Animesh Acharjee
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Center for Computational Biology, University of Birmingham, UK,Institute of Translational Medicine, University Hospitals Birmingham Nhs, Foundation Trust, UK,Nihr Surgical Reconstruction and Microbiology Research Center, University Hospital Birmingham, Birmingham, UK
| | - Mohammed N Quraishi
- Department of Gastroenterology, University Hospitals Birmingham Nhs Foundation Trust, Birmingham, UK,Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK,University of Birmingham Microbiome Treatment Center, University of Birmingham, UK,Center for Liver and Gastroenterology Research, Nihr Birmingham Biomedical Research Center, University of Birmingham, Birmingham, UK
| | - Patricia Rojas
- Institute of Applied Health Research, University of Birmingham, UK
| | - Abdellatif Bakkali
- Department of Clinical Chemistry, Vu University Medical Center, Amsterdam, The Netherlands
| | - Erwin EW Jansen
- Department of Clinical Chemistry, Vu University Medical Center, Amsterdam, The Netherlands
| | - Marina Brizzio Brentar
- Amsterdam Umc, Vu University Medical Center, Department of Gastroenterology and Hepatology, Ag&m Research Institute, Amsterdam, The Netherlands
| | - Johan Kuijvenhoven
- Spaarne Gasthuis, Department of Gastroenterology and Hepatology, Spaarne Gasthuis (primary institute), Hoofddorp and Haarlem, The Netherlands
| | - Pieter Stokkers
- Olvg West, Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis West, Amsterdam, The Netherlands
| | - Eduard Struys
- Department of Clinical Chemistry, Vu University Medical Center, Amsterdam, The Netherlands
| | - Andrew D Beggs
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | - Georgios V Gkoutos
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Center for Computational Biology, University of Birmingham, UK,Institute of Translational Medicine, University Hospitals Birmingham Nhs, Foundation Trust, UK,Nihr Surgical Reconstruction and Microbiology Research Center, University Hospital Birmingham, Birmingham, UK,Medical Research Counsil, MRC Health Data Research, UK,NIHR Experimental Cancer Medicine Center, National Institute for Health Research, Birmingham, UK,NIHR Biomedical Research Center, University Hospital Birmingham, Birmingham, UK
| | - Tim GJ de Meij
- Amsterdam Umc, Vu University Amsterdam, Department of Paediatric Gastroenterology, Ag&m Research Institute, Amsterdam, The Netherlands
| | - Nanne KH de Boer
- Amsterdam Umc, Vu University Medical Center, Department of Gastroenterology and Hepatology, Ag&m Research Institute, Amsterdam, The Netherlands
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14
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Cronin P, Murphy CL, Barrett M, Ghosh TS, Pellanda P, O'Connor EM, Zulquernain SA, Kileen S, McCourt M, Andrews E, O'Riordain MG, Shanahan F, O'Toole PW. Colorectal microbiota after removal of colorectal cancer. NAR Cancer 2022; 4:zcac011. [PMID: 35399186 PMCID: PMC8991967 DOI: 10.1093/narcan/zcac011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 03/08/2022] [Accepted: 04/04/2022] [Indexed: 01/01/2023] Open
Abstract
The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled the microbiota using 16S rRNA gene amplicon sequencing in colonic biopsies from patients after resection of CRC (n = 63) in comparison with controls (n = 52), subjects with newly diagnosed CRC (n = 93) and polyps (i = 28). The colonic microbiota after surgical resection remained significantly different from that of controls in 65% of patients. Genus-level profiling and beta-diversity confirmed two distinct groups of patients after resection of CRC: one with an abnormal microbiota similar to that of patients with newly diagnosed CRC and another similar to non-CRC controls. Consumption levels of several dietary ingredients and cardiovascular drugs co-varied with differences in microbiota composition suggesting lifestyle factors may modulate differential microbiome trajectories after surgical resection. This study supports investigation of the colonic microbiota as a marker of risk for development of CRC.
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Affiliation(s)
- Peter Cronin
- Department of Biological Science, University of Limerick, Limerick, V94 T9PX, Ireland
| | - Clodagh L Murphy
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
| | - Maurice Barrett
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
| | | | - Paola Pellanda
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
| | - Eibhlis M O'Connor
- Department of Biological Science, University of Limerick, Limerick, V94 T9PX, Ireland
| | | | - Shane Kileen
- Cork University Hospital, Cork, T12 DC4A, Ireland
| | | | | | | | - Fergus Shanahan
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
| | - Paul W O'Toole
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
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15
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Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits. mSystems 2022; 7:e0001822. [PMID: 35311577 PMCID: PMC9040882 DOI: 10.1128/msystems.00018-22] [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] [Indexed: 12/24/2022] Open
Abstract
The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood.
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16
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Xu Y, Nash K, Acharjee A, Gkoutos GV. CACONET: a novel classification framework for microbial correlation networks. Bioinformatics 2022; 38:1639-1647. [PMID: 34983063 PMCID: PMC8896646 DOI: 10.1093/bioinformatics/btab879] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 12/15/2021] [Accepted: 12/30/2021] [Indexed: 02/03/2023] Open
Abstract
MOTIVATION Existing microbiome-based disease prediction relies on the ability of machine learning methods to differentiate disease from healthy subjects based on the observed taxa abundance across samples. Despite numerous microbes have been implicated as potential biomarkers, challenges remain due to not only the statistical nature of microbiome data but also the lack of understanding of microbial interactions which can be indicative of the disease. RESULTS We propose CACONET (classification of Compositional-Aware COrrelation NETworks), a computational framework that learns to classify microbial correlation networks and extracts potential signature interactions, taking as input taxa relative abundance across samples and their health status. By using Bayesian compositional-aware correlation inference, a collection of posterior correlation networks can be drawn and used for graph-level classification, thus incorporating uncertainty in the estimates. CACONET then employs a deep learning approach for graph classification, achieving excellent performance metrics by exploiting the correlation structure. We test the framework on both simulated data and a large real-world dataset pertaining to microbiome samples of colorectal cancer (CRC) and healthy subjects, and identify potential network substructure characteristic of CRC microbiota. CACONET is customizable and can be adapted to further improve its utility. AVAILABILITY AND IMPLEMENTATION CACONET is available at https://github.com/yuanwxu/corr-net-classify. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Yuanwei Xu
- To whom correspondence should be addressed.
| | - Katrina Nash
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK
| | - Animesh Acharjee
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK,NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham B15 2TT, UK,Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK,MRC Health Data Research UK (HDR), Midlands Site B15 2TT, UK
| | - Georgios V Gkoutos
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK,NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham B15 2TT, UK,Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TT, UK,MRC Health Data Research UK (HDR), Midlands Site B15 2TT, UK
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17
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Bai J, Barandouzi ZA, Rowcliffe C, Meador R, Tsementzi D, Bruner DW. Gut Microbiome and Its Associations With Acute and Chronic Gastrointestinal Toxicities in Cancer Patients With Pelvic Radiation Therapy: A Systematic Review. Front Oncol 2021; 11:745262. [PMID: 34938654 PMCID: PMC8685326 DOI: 10.3389/fonc.2021.745262] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
Aim Pelvic radiation therapy (RT) can impact the gut microbiome in patients with cancer and result in gastrointestinal (GI) toxicities. The purpose of this systematic review was to describe the effects of RT on the gut microbiome and the associations between the gut microbiome and GI toxicities in patients treated with pelvic RT. Methods PubMed, Embase, and Web of Science databases were searched from their earliest records to August 2020. The articles screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Mixed Method Assessment Tool was used to assess the methodological quality for each included study. All study findings were synthesized and presented in narrative format. Thirteen studies were included. The gut microbiome of fecal samples was analyzed using 16S rRNA sequencing approaches. Results There were disparities in alpha and beta diversities that existed across the studies. Divergent results were found among various phyla, including Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Cyanobacteria, Fusobacteria, and Deinococcus-Thermus. Moreover, alteration in the gut microbiome diversity and abundance related to cancer treatment was associated with pelvic toxicities, specifically diarrhea. Following treatment, increases in the abundance of Bacteroides was associated with diarrhea and radiation enteritis. Conclusions Pelvic RT can disrupt the diversity and abundance of commensal gut microorganisms. A dysbiotic gut microbiome showed a promising association with radiation enteritis through alterations of the intestinal barrier function, innate immunity, and intestinal repair mechanisms; however, confounders, such as diet, were not thoroughly addressed.
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Affiliation(s)
- Jinbing Bai
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, United States.,Winship Cancer Institute, Emory University, Atlanta, GA, United States
| | - Zahra A Barandouzi
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, United States
| | - Claire Rowcliffe
- Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Rebecca Meador
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, United States
| | - Despina Tsementzi
- Rollins School of Public Health, Emory University, Atlanta, GA, United States
| | - Deborah Watkins Bruner
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, United States.,Winship Cancer Institute, Emory University, Atlanta, GA, United States
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18
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Zhang T, Chen L, Ding H, Wu PF, Zhang GX, Pan ZM, Xie KZ, Dai GJ, Wang JY. The Potential Effect of Microbiota in Predicting The Freshness of Chilled Chicken. Br Poult Sci 2021; 63:360-367. [PMID: 34747672 DOI: 10.1080/00071668.2021.2003753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
1. The goals of this study were to analyse the changes in microbiota composition of chilled chicken during storage and identify microbial biomarkers related to meat freshness.2. The study used 16S rDNA sequencing to track the microbiota shift in chilled chicken during storage. Associations between microbiota composition and storage time were analysed and microbial biomarkers were identified.3. The results showed that microbial diversity of chilled chicken decreased with the storage time. A total of 27 and 24 microbial biomarkers were identified by using orthogonal partial least squares (OPLS) and the random forest regression approach, respectively. The receiver operating characteristic (ROC) curve analysis indicated that the OPLS regression approach had better performance in identifying freshness-related biomarkers. The multiple stepwise regression analysis identified four key microbial biomarkers, including Streptococcus, Carnobacterium, Serratia and Photobacterium genera and constructed a predictive model.4. The study provided microbial biomarkers and a model related to the freshness of chilled chicken. These findings provide a basis for developing detection methods of the freshness of chilled chicken.
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Affiliation(s)
- T Zhang
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - L Chen
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,College of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu, China
| | - H Ding
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - P F Wu
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - G X Zhang
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - Z M Pan
- Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - K Z Xie
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - G J Dai
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
| | - J Y Wang
- College of Animal Science and Technology, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China.,Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education, Yangzhou University, 48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
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19
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Aarnoutse R, Ziemons J, de Vos-Geelen J, Valkenburg-van Iersel L, Wildeboer ACL, Vievermans A, Creemers GJM, Baars A, Vestjens HJHMJ, Le GN, Barnett DJM, Rensen SS, Penders J, Smidt ML. The Role of Intestinal Microbiota in Metastatic Colorectal Cancer Patients Treated With Capecitabine. Clin Colorectal Cancer 2021; 21:e87-e97. [PMID: 34801414 DOI: 10.1016/j.clcc.2021.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 09/29/2021] [Accepted: 10/13/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Previous pre-clinical research has indicated that the intestinal microbiota can potentiate anti-tumour efficacy of capecitabine and that capecitabine treatment impacts intestinal microbiota composition and diversity. Using a longitudinal design, this study explores the associations between the intestinal microbiota and treatment response in patients with metastatic colorectal cancer (mCRC) during capecitabine treatment. PATIENTS AND METHODS Patients with mCRC treated with capecitabine were prospectively enrolled in a multicentre cohort study. Patients collected a faecal sample and completed a questionnaire before, during, and after three cycles of capecitabine. Several clinical characteristics, including tumour response, toxicity and antibiotic use were recorded. Intestinal microbiota were analysed by amplicon sequencing of the 16S rRNA V4 gene-region. RESULTS Thirty-three patients were included. After three cycles of capecitabine, six patients (18%) achieved a partial response, 25 (76%) showed stable disease, and one (3%) experienced progressive disease. Of the 90 faecal samples were collected. Microbial diversity (α-diversity), community structure (β-diversity), and bacterial abundance on phylum and genus level were not significantly different between responders and non-responders and were not significantly affected by three cycles of capecitabine. CONCLUSION This is the first clinical study with longitudinal intestinal microbiota sampling in mCRC patients that explores the role of the intestinal microbiota during treatment with capecitabine. Intestinal microbiota composition and diversity before, during, and after three cycles of capecitabine were not associated with response in this study population. Capecitabine did not induce significant changes in the microbiota composition and diversity during the treatment period. Individual effects of antibiotics during capecitabine treatment were observed.
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Affiliation(s)
- Romy Aarnoutse
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Janine Ziemons
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Judith de Vos-Geelen
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Internal Medicine, Division of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Liselot Valkenburg-van Iersel
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Internal Medicine, Division of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Aurelia C L Wildeboer
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Anne Vievermans
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
| | | | - Arnold Baars
- Department of Medical Oncology, Hospital Gelderse Vallei, Ede, The Netherlands
| | | | - Giang N Le
- Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - David J M Barnett
- Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands
| | - Sander S Rensen
- Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands; NUTRIM - School of Nutrition and Translational research In Metabolism, Maastricht University, Maastricht, The Netherlands
| | - John Penders
- Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands; NUTRIM - School of Nutrition and Translational research In Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Marjolein L Smidt
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
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20
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Xue JH, Xie YH, Zou TH, Qian Y, Kang ZR, Zhou CB, Pan SY, Xia TX, Chen YX, Fang JY. Fecal Fusobacterium nucleatum as a predictor for metachronous colorectal adenoma after endoscopic polypectomy. J Gastroenterol Hepatol 2021; 36:2841-2849. [PMID: 34121231 DOI: 10.1111/jgh.15559] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 04/02/2021] [Accepted: 05/19/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Fusobacterium nucleatum is increasingly being recognized as an important risk factor in colorectal cancer and colorectal adenoma. Endoscopic polypectomy is associated with a decreased incidence of colorectal cancer; however, patients still suffer from a risk of metachronous adenoma. Currently, there are few effective non-invasive factors that may predict metachronous colorectal adenoma. Here, we evaluated the performance of F. nucleatum in predicting metachronous adenoma. METHODS Fecal samples and clinical information of patients before endoscopic polypectomy were collected from 367 patients in a retrospective cohort, and 238 patients in a prospective cohort. The abundance of fecal F. nucleatum was measured via quantitative polymerase chain reaction. Surveillance colonoscopies were conducted between 1 and 3 years after polypectomy (average follow-up 27.07 months for the retrospective cohort & 22.57 months for the prospective cohort) to identify metachronous adenoma. Candidate predictive factors and cut-off value of F. nucleatum abundance were identified from the retrospective cohort and then validated in the prospective cohort. RESULTS A high abundance of fecal F. nucleatum was found to be an independent risk factor for metachronous adenomas (odds ratio, 6.38; P < 0.001) in the retrospective cohort and was validated in the prospective cohort with a specificity of 65.00%, and a sensitivity of 73.04%, and an overall performance with the area under the curve of 0.73. CONCLUSION Fecal abundance of F. nucleatum may be a reliable predictor for metachronous adenoma after endoscopic polypectomy.
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Affiliation(s)
- Jin-Hui Xue
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan-Hong Xie
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian-Hui Zou
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Qian
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zi-Ran Kang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Cheng-Bei Zhou
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Si-Yuan Pan
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian-Xue Xia
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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21
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The Association of Gut Microbiota and Complications in Gastrointestinal-Cancer Therapies. Biomedicines 2021; 9:biomedicines9101305. [PMID: 34680424 PMCID: PMC8533200 DOI: 10.3390/biomedicines9101305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 12/24/2022] Open
Abstract
The therapy of gastrointestinal carcinomas includes surgery, chemo- or immunotherapy, and radiation with diverse complications such as surgical-site infection and enteritis. In recent years, the microbiome’s influence on different diseases and complications has been studied in more detail using methods such as next-generation sequencing. Due to the relatively simple collectivisation, the gut microbiome is the best-studied so far. While certain bacteria are sometimes associated with one particular complication, it is often just the loss of alpha diversity linked together. Among others, a strong influence of Fusobacterium nucleatum on the effectiveness of chemotherapies is demonstrated. External factors such as diet or specific medications can also predispose to dysbiosis and lead to complications. In addition, there are attempts to treat developed dysbiosis, such as faecal microbiota transplant or probiotics. In the future, the underlying microbiome should be investigated in more detail for a better understanding of the precipitating factors of a complication with specific therapeutic options.
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22
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Nouri R, Hasani A, Shirazi KM, Aliand MR, Sepehri B, Sotoodeh S, Hemmati F, Rezaee MA. Escherichia coli and colorectal cancer: Unfolding the enigmatic relationship. Curr Pharm Biotechnol 2021; 23:1257-1268. [PMID: 34514986 DOI: 10.2174/1389201022666210910094827] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/21/2021] [Accepted: 06/07/2021] [Indexed: 11/22/2022]
Abstract
Colorectal cancer (CRC) is one of the deadliest cancers in the world. Specific strains of intestinal Escherichia coli (E. coli) may influence the initiation and development of CRC by exploiting virulence factors and inflammatory pathways. Mucosa-associated E. coli strains are more prevalent in CRC biopsies in comparison to healthy controls. Moreover, these strains can survive and replicate within macrophages and induce a pro-inflammatory response. Chronic exposure to inflammatory mediators can lead to increased cell proliferation and cancer. Production of colobactin toxin by the majority of mucosa-associated E. coli isolated from CRC patients is another notable finding. Colibactin-producing E. coli strains, in particular, induce double-strand DNA breaks, stop the cell cycle, involve in chromosomal rearrangements of mammalian cells and are implicated in carcinogenic effects in animal models. Moreover, some enteropathogenic E. coli (EPEC) strains are able to survive and replicate in colon cells as chronic intracellular pathogens and may promote susceptibility to CRC by downregulation of DNA Mismatch Repair (MMR) proteins. In this review, we discuss current evidence and focus on the mechanisms by which E. coli can influence the development of CRC.
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Affiliation(s)
- Rogayeh Nouri
- 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
| | - Kourosh Masnadi Shirazi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Mohammad Reza Aliand
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Bita Sepehri
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Simin Sotoodeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz. Iran
| | - Fatemeh Hemmati
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz. Iran
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23
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Chen Y, Liu P, Liu R, Hu S, He Z, Dong G, Feng C, An S, Ying X. Comprehensive Strain-Level Analysis of the Gut Microbe Faecalibacterium prausnitzii in Patients with Liver Cirrhosis. mSystems 2021; 6:e0077521. [PMID: 34342541 PMCID: PMC8407477 DOI: 10.1128/msystems.00775-21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 07/09/2021] [Indexed: 01/11/2023] Open
Abstract
Liver cirrhosis (LC) has been associated with gut microbes. However, the strain diversity of species and its association with LC have received little attention. Here, we constructed a computational framework to study the strain heterogeneity in the gut microbiome of patients with LC. Only Faecalibacterium prausnitzii shows different single-nucleotide polymorphism (SNP) patterns between the LC and healthy control (HC) groups. Strain diversity analysis discovered that although most F. prausnitzii genomes are more deficient in the LC group than in the HC group at the strain level, a subgroup of 19 F. prausnitzii strains showed no sensitivity to LC, which is inconsistent with the species-level result. The functional differences between this subgroup and other strains may involve short-chain fatty acid production and chlorine-related pathways. These findings demonstrate functional differences among F. prausnitzii subgroups, which extend current knowledge about strain heterogeneity and relationships between F. prausnitzii and LC at the strain level. IMPORTANCE Most metagenomic studies focus on microbes at the species level, thus ignoring the different effects of different strains of the same species on the host. In this study, we explored the different microbes at the strain level in the intestines of patients with liver cirrhosis and of healthy people. Previous studies have shown that the species Faecalibacterium prausnitzii has a lower abundance in patients with liver cirrhosis than in healthy people. However, our results found multiple F. prausnitzii strains that do not decrease in abundance in patients with liver cirrhosis. It is more sensitive to select the appropriate strains as indicators to distinguish between the disease and the control samples than to use the entire species as an indicator. We clustered multiple F. prausnitzii strains and discuss the functional differences of different clusters. Our findings suggest that more attention should be paid to metagenomic studies at the strain level.
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Affiliation(s)
- Yaowen Chen
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Pu Liu
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Runyan Liu
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Shuofeng Hu
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Zhen He
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Guohua Dong
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Chao Feng
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Sijing An
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Xiaomin Ying
- Center for Computational Biology, Beijing Institute of Basic Medical Sciences, Beijing, China
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24
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Bisht V, Acharjee A, Gkoutos GV. NFnetFu: A novel workflow for microbiome data fusion. Comput Biol Med 2021; 135:104556. [PMID: 34216888 PMCID: PMC8404037 DOI: 10.1016/j.compbiomed.2021.104556] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 06/04/2021] [Accepted: 06/04/2021] [Indexed: 12/18/2022]
Abstract
Microbiome data analysis and its interpretation into meaningful biological insights remain very challenging for numerous reasons, perhaps most prominently, due to the need to account for multiple factors, including collinearity, sparsity (excessive zeros) and effect size, that the complex experimental workflow and subsequent downstream data analysis require. Moreover, a meaningful microbiome data analysis necessitates the development of interpretable models that incorporate inferences across available data as well as background biomedical knowledge. We developed a multimodal framework that considers sparsity (excessive zeros), lower effect size, intrinsically microbial correlations, i.e., collinearity, as well as background biomedical knowledge in the form of a cluster-infused enriched network architecture. Finally, our framework also provides a candidate taxa/Operational Taxonomic Unit (OTU) that can be targeted for future validation experiments. We have developed a tool, the term NFnetFU (Neuro Fuzzy network Fusion), that encompasses our framework and have made it freely available at https://github.com/VartikaBisht6197/NFnetFu.
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Affiliation(s)
- Vartika Bisht
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, B15 2TT, UK
| | - Animesh Acharjee
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, B15 2TT, UK; Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust, B15 2TT, UK; NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham, B15 2WB, UK; MRC Health Data Research UK HDR, UK.
| | - Georgios V Gkoutos
- College of Medical and Dental Sciences, Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, B15 2TT, UK; Institute of Translational Medicine, University Hospitals Birmingham NHS, Foundation Trust, B15 2TT, UK; NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham, B15 2WB, UK; MRC Health Data Research UK HDR, UK; NIHR Experimental Cancer Medicine Centre, B15 2TT, Birmingham, UK; NIHR Biomedical Research Centre, University Hospital Birmingham, Birmingham, B15 2TT, UK
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25
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Aprile F, Bruno G, Palma R, Mascellino MT, Panetta C, Scalese G, Oliva A, Severi C, Pontone S. Microbiota Alterations in Precancerous Colon Lesions: A Systematic Review. Cancers (Basel) 2021; 13:cancers13123061. [PMID: 34205378 PMCID: PMC8234190 DOI: 10.3390/cancers13123061] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/09/2021] [Accepted: 06/14/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Even with recent advances, gut microbiota is still one of the most demanding challenges that research needs to handle. In particular, given its deep impact on gastrointestinal health, microbiota could explain the development and progression of certain diseases. Moreover, it could be used as a potential predictive biomarker. Given this, the relationship between intestinal microbiota and colorectal adenoma, considered a premalignant lesion leading to carcinoma, has been deeply evaluated. This review highlights the historical and novel data on microbiota characteristics in adenoma patients to provide an updated summary of current knowledge and its limits. Abstract Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma–carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using “adenoma microbiota” and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of Clostridium, Faecalibacterium, Bacteroides and Romboutsia. Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma’s endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.
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Affiliation(s)
- Francesca Aprile
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Giovanni Bruno
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Rossella Palma
- Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.P.); (C.P.)
| | - Maria Teresa Mascellino
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy; (M.T.M.); (A.O.)
| | - Cristina Panetta
- Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.P.); (C.P.)
| | - Giulia Scalese
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy; (M.T.M.); (A.O.)
| | - Carola Severi
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Stefano Pontone
- Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.P.); (C.P.)
- Correspondence: ; Tel.: +39-06-49975568
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26
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Wu Y, Jiao N, Zhu R, Zhang Y, Wu D, Wang AJ, Fang S, Tao L, Li Y, Cheng S, He X, Lan P, Tian C, Liu NN, Zhu L. Identification of microbial markers across populations in early detection of colorectal cancer. Nat Commun 2021; 12:3063. [PMID: 34031391 PMCID: PMC8144394 DOI: 10.1038/s41467-021-23265-y] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 04/20/2021] [Indexed: 02/07/2023] Open
Abstract
Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-L-glycero-beta-D-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.
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Affiliation(s)
- Yuanqi Wu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China
| | - Na Jiao
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ruixin Zhu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
| | - Yida Zhang
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
| | - Dingfeng Wu
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China
| | - An-Jun Wang
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Sa Fang
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China
| | - Liwen Tao
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China
| | - Yichen Li
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Sijing Cheng
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
- School of Medicine, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Xiaosheng He
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ping Lan
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
- School of Medicine, Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Chuan Tian
- Department of Gastroenterology, The Shanghai Tenth People's Hospital, Department of Bioinformatics, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
| | - Ning-Ning Liu
- State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
| | - Lixin Zhu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
- Genome, Environment and Microbiome Community of Excellence, The State University of New York at Buffalo, Buffalo, NY, USA.
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27
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Gastrointestinal cancers: the role of microbiota in carcinogenesis and the role of probiotics and microbiota in anti-cancer therapy efficacy. Cent Eur J Immunol 2021; 45:476-487. [PMID: 33658894 PMCID: PMC7882408 DOI: 10.5114/ceji.2020.103353] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 09/24/2019] [Indexed: 02/06/2023] Open
Abstract
The gut epithelium is a habitat of a variety of microorganisms, including bacteria, fungi, viruses and Archaea. With the advent of sophisticated molecular techniques and bioinformatics tools, more information on the composition and thus function of gut microbiota was revealed. The gut microbiota as an integral part of the intestinal barrier has been shown to be involved in shaping the mucosal innate and adaptive immune response and to provide protection against pathogens. Consequently, a set of biochemical signals exchanged within microbes and communication between the microbiota and the host have opened a new way of thinking about cancer biology. Probiotics are living organisms which administered in adequate amounts may bring health benefits and have the potential to be an integral part of the prevention/treatment strategies in clinical approaches. Here we provide a comprehensive review of data linking gut microbiota to cancer pathogenesis and its clinical course. We focus on gastrointestinal cancers, such as gastric, colorectal, pancreatic and liver cancer.
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28
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Vernia F, Longo S, Stefanelli G, Viscido A, Latella G. Dietary Factors Modulating Colorectal Carcinogenesis. Nutrients 2021; 13:nu13010143. [PMID: 33401525 PMCID: PMC7824178 DOI: 10.3390/nu13010143] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/28/2020] [Accepted: 12/29/2020] [Indexed: 12/14/2022] Open
Abstract
The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.
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29
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Jin Y, Geng R, Liu Y, Liu L, Jin X, Zhao F, Feng J, Wei Y. Prediction of Postoperative Ileus in Patients With Colorectal Cancer by Preoperative Gut Microbiota. Front Oncol 2020; 10:526009. [PMID: 33324541 PMCID: PMC7724052 DOI: 10.3389/fonc.2020.526009] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 09/21/2020] [Indexed: 12/16/2022] Open
Abstract
Background Ileus and postoperative ileus (POI) are common complications of colorectal cancer (CRC). However, little is known about the gut microbiota associated with ileus. Method Differences in gut microbiota were evaluated by 16S rRNA gene sequencing. We characterized the gut microbiota in 85 CRC patients (cohort 1) and detected differences, and an independent cohort composed of 38 CRC patients (cohort 2) was used to evaluate the results. Results The gut microbiota of CRC patients with and without ileus exhibited large differences in alpha- and beta-diversities and bacterial taxa. The Firmicutes-to-Bacteroidetes ratio and microbial dysbiosis index (MDI) showed greater dysbiosis among ileus patients than among those without ileus. According to the location of CRC, the difference in gut microbiota between patients with and without ileus was more obvious in those with distal CRC than in those with proximal CRC. Finally, Faecalibacterium was significantly reduced in the postoperative perioperative period in patients with ileus. Thus, we used Faecalibacterium as a biomarker for predicting perioperative or POI: the AUC value was 0.74 for perioperative ileus and 0.67 for POI that appeared at 6 months after hospital discharge. The predictive power was evaluated in Cohort 2, with an AUC value of 0.79. Conclusion These findings regarding difference of gut microbiota in postoperative CRC patients may provide a theoretical basis for the use of microbiota as biomarkers for the prediction of POI.
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Affiliation(s)
- Ye Jin
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rui Geng
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Department of Thyroid and Breast Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Yang Liu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lujia Liu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiangren Jin
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Fuya Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jing Feng
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunwei Wei
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.,Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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30
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Ferrarese R, Zuppardo RA, Puzzono M, Mannucci A, Amato V, Ditonno I, Patricelli MG, Raucci AR, Clementi M, Elmore U, Rosati R, Testoni PA, Mancini N, Cavestro GM. Oral and Fecal Microbiota in Lynch Syndrome. J Clin Med 2020; 9:jcm9092735. [PMID: 32847083 PMCID: PMC7563889 DOI: 10.3390/jcm9092735] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 08/17/2020] [Accepted: 08/19/2020] [Indexed: 12/11/2022] Open
Abstract
Background: The role of microbiota in Lynch syndrome (LS) is still under debate. We compared oral and fecal microbiota of LS saliva and stool samples with normal healthy controls (NHC). Methods: Total DNA was purified from feces and saliva to amplify the V3–V4 region of the 16s rRNA gene. Sequences with a high-quality score and length >250 bp were used for taxonomic analysis with QIIME software. Results: Compared to NHC, LS fecal samples demonstrated a statistically significant increase of Bacteroidetes and Proteobacteria and a significant decrease of Firmicutes at the phylum level and of Ruminococcaceae at the family level. Moreover, LS oral samples exhibited a statistically significant increase of Veillonellaceae and Leptotrichiaceae and a statistically significant decrease of Pasteurellaceae. A beta-diversity index allowed differentiation of the two groups. Conclusions: A peculiar microbial signature is associated with LS, similar to that of sporadic colorectal cancer and Crohn’s disease. These data suggest a possible role of proinflammatory bacteria in tumor development in a condition of genetic predisposition, such as LS.
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Affiliation(s)
- Roberto Ferrarese
- Microbiology and Virology Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.F.); (V.A.); (M.C.); (N.M.)
| | - Raffaella Alessia Zuppardo
- Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.A.Z.); (M.P.); (P.A.T.)
| | - Marta Puzzono
- Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.A.Z.); (M.P.); (P.A.T.)
| | - Alessandro Mannucci
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
| | - Virginia Amato
- Microbiology and Virology Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.F.); (V.A.); (M.C.); (N.M.)
| | - Ilaria Ditonno
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
| | - Maria Grazia Patricelli
- Division of Genetics and Cell Biology and Laboratory of Clinical Molecular Biology and Cytogenetics, Unit of Genomics for Human Disease Diagnosis, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (M.G.P.); (A.R.R.)
| | - Annalisa Russo Raucci
- Division of Genetics and Cell Biology and Laboratory of Clinical Molecular Biology and Cytogenetics, Unit of Genomics for Human Disease Diagnosis, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (M.G.P.); (A.R.R.)
| | - Massimo Clementi
- Microbiology and Virology Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.F.); (V.A.); (M.C.); (N.M.)
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
| | - Ugo Elmore
- Department of Gastrointestinal Surgery, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy;
| | - Riccardo Rosati
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
- Department of Gastrointestinal Surgery, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy;
| | - Pier Alberto Testoni
- Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.A.Z.); (M.P.); (P.A.T.)
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
| | - Nicasio Mancini
- Microbiology and Virology Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.F.); (V.A.); (M.C.); (N.M.)
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
| | - Giulia Martina Cavestro
- Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Ospedale San Raffaele Scientific Institute, 20132 Milan, Italy; (R.A.Z.); (M.P.); (P.A.T.)
- Vita-Salute San Raffaele University, 20132 Milan, Italy; (A.M.); (I.D.); (R.R.)
- Correspondence: ; Tel.: +39-022-643-5508
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Park SS, Kim B, Kim MJ, Roh SJ, Park SC, Kim BC, Han KS, Hong CW, Sohn DK, Oh JH. The effect of curative resection on fecal microbiota in patients with colorectal cancer: a prospective pilot study. Ann Surg Treat Res 2020; 99:44-51. [PMID: 32676481 PMCID: PMC7332315 DOI: 10.4174/astr.2020.99.1.44] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 03/03/2020] [Accepted: 04/10/2020] [Indexed: 01/04/2023] Open
Abstract
Purpose Although many studies have evaluated the association between intestinal microorganisms and the risk of colorectal cancer (CRC), only a few studies have investigated the changes in microorganisms following curative treatment for CRC. The current study analyzed changes in intestinal microbiota following curative surgery in CRC patients. Methods Stool samples were collected before and 6 months after surgery, from 11 patients with clinical stage III CRC, who underwent curative surgery between May 2017 and June 2017. Next, 16S rRNA gene sequencing was performed. Operational taxonomic units (OTUs) and alpha diversity were evaluated using the Shannon index. The bacterial compositions of the stools were analyzed according to taxonomic rank at genus and phylum levels. Results OTUs and alpha diversity were significantly decreased following surgery (P < 0.001 and P = 0.019, respectively). The compositions of several bacterial taxa changed after surgery. At genus level, proportions of pathogens such as Campylobacter, Fusobacterium, Haemophilus, Porphyromonas, and Prevotella, decreased after surgery (adjusted P < 0.05). At phylum level, the proportion of Fusobacteria decreased after surgery (adjusted P < 0.001). Conclusion Significant changes in intestinal microbial communities were noted following curative resection of CRC patients. Especially, decreases in pathogenic bacterial populations, such as Fusobacterium and Prevotella, which are known to be associated with CRC development, were detected even though OTUs and alpha diversity were decreased following curative resection. To determine and validate the clinical significance of these findings, large scale, prospective studies that include cancer prognoses are required.
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Affiliation(s)
- Sung Sil Park
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Bun Kim
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Min Jung Kim
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Seung Jae Roh
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sung Chan Park
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Byung Chang Kim
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Kyung Su Han
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Chang Won Hong
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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32
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Liu Y, Geng R, Liu L, Jin X, Yan W, Zhao F, Wang S, Guo X, Ghimire G, Wei Y. Gut Microbiota-Based Algorithms in the Prediction of Metachronous Adenoma in Colorectal Cancer Patients Following Surgery. Front Microbiol 2020; 11:1106. [PMID: 32595614 PMCID: PMC7303296 DOI: 10.3389/fmicb.2020.01106] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 05/04/2020] [Indexed: 01/01/2023] Open
Abstract
Evaluating the risk of colorectal metachronous adenoma (MA), which is a precancerous lesion, is necessary for metachronous colorectal cancer (CRC) precaution among CRC patients who had underwent surgical removal of their primary tumor. Here, discovery cohort (n = 41) and validation cohort (n = 45) of CRC patients were prospectively enrolled in this study. Mucosal and fecal samples were used for gut microbiota analysis by sequencing the 16S rRNA genes. Significant reduction of microbial diversity was noted in MA (P < 0.001). A signature defined by decreased abundance of eight genera and increased abundance of two genera strongly correlated with MA. The microbiota-based random forest (RF) model, established utilizing Escherichia–Shigella, Acinetobacter together with BMI in combination, achieved AUC values of 0.885 and 0.832 for MA, predicting in discovery and validation cohort, respectively. The RF model was performed as well for fecal and tumor adjacent mucosal samples with an AUC of 0.835 and 0.889, respectively. Gut microbiota profile of MA still existed in post-operative cohort patients, but the RF model could not be performed well on this cohort, with an AUC of 0.61. Finally, we introduced a risk score based on Escherichia–Shigella, Acinetobacter and BMI, and synchronous-adenoma achieved AUC values of 0.94 and 0.835 in discovery and validation cohort, respectively. This study presented a comprehensive landscape of gut microbiota in MA, demonstrated that the gut microbiota-based models and scoring system achieved good ability to predict the risk for developing MA after surgical resection. Our study suggests that gut microbiota is a potential predictive biomarker for MA.
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Affiliation(s)
- Yang Liu
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rui Geng
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lujia Liu
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiangren Jin
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wei Yan
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Fuya Zhao
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shuang Wang
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiao Guo
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ghanashyam Ghimire
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yunwei Wei
- Department of Oncological and Endoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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Bartolini I, Risaliti M, Ringressi MN, Melli F, Nannini G, Amedei A, Muiesan P, Taddei A. Role of gut microbiota-immunity axis in patients undergoing surgery for colorectal cancer: Focus on short and long-term outcomes. World J Gastroenterol 2020; 26:2498-2513. [PMID: 32523307 PMCID: PMC7265137 DOI: 10.3748/wjg.v26.i20.2498] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/27/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent. The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a pro-inflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course; dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis (and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.
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Affiliation(s)
- Ilenia Bartolini
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Matteo Risaliti
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Maria Novella Ringressi
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Filippo Melli
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Giulia Nannini
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Paolo Muiesan
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Antonio Taddei
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
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34
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Yan Y, Drew DA, Markowitz A, Lloyd-Price J, Abu-Ali G, Nguyen LH, Tran C, Chung DC, Gilpin KK, Meixell D, Parziale M, Schuck M, Patel Z, Richter JM, Kelsey PB, Garrett WS, Chan AT, Stadler ZK, Huttenhower C. Structure of the Mucosal and Stool Microbiome in Lynch Syndrome. Cell Host Microbe 2020; 27:585-600.e4. [PMID: 32240601 PMCID: PMC7453618 DOI: 10.1016/j.chom.2020.03.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 11/22/2019] [Accepted: 03/10/2020] [Indexed: 12/12/2022]
Abstract
The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.
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Affiliation(s)
- Yan Yan
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - David A Drew
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Arnold Markowitz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jason Lloyd-Price
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Galeb Abu-Ali
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Long H Nguyen
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Christina Tran
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Daniel C Chung
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Katherine K Gilpin
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Dana Meixell
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Melanie Parziale
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Madeline Schuck
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Zalak Patel
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Peter B Kelsey
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Wendy S Garrett
- Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Immunology & Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
| | - Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Immunology & Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths in both the USA and the world. Recent research has demonstrated the involvement of the gut microbiota in CRC development and progression. Microbial biomarkers of disease have focused primarily on the bacterial component of the microbiome; however, the viral portion of the microbiome, consisting of both bacteriophages and eukaryotic viruses, together known as the virome, has been lesser studied. Here we review the recent advancements in high-throughput sequencing (HTS) technologies and bioinformatics, which have enabled scientists to better understand how viruses might influence the development of colorectal cancer. We discuss the contemporary findings revealing modulations in the virome and their correlation with CRC development and progression. While a variety of challenges still face viral HTS detection in clinical specimens, we consider herein numerous next steps for future basic and clinical research. Clinicians need to move away from a single infectious agent model for disease etiology by grasping new, more encompassing etiological paradigms, in which communities of various microbial components interact with each other and the host. The reporting and indexing of patient health information, socioeconomic data, and other relevant metadata will enable identification of predictive variables and covariates of viral presence and CRC development. Altogether, the virome has a more profound role in carcinogenesis and cancer progression than once thought, and viruses, specific for either human cells or bacteria, are clinically relevant in understanding CRC pathology, patient prognosis, and treatment development.
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36
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Sun W, Wang L, Zhang Q, Dong Q. Microbial Biomarkers for Colorectal Cancer Identified with Random Forest Model. EXPLORATORY RESEARCH AND HYPOTHESIS IN MEDICINE 2020; 000:1-000. [DOI: 10.14218/erhm.2019.00026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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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: 20] [Impact Index Per Article: 3.3] [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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38
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Yu SY, Xie YH, Qiu YW, Chen YX, Fang JY. Moderate alteration to gut microbiota brought by colorectal adenoma resection. J Gastroenterol Hepatol 2019; 34:1758-1765. [PMID: 31115072 DOI: 10.1111/jgh.14735] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/31/2019] [Accepted: 04/28/2019] [Indexed: 12/24/2022]
Abstract
UNLABELLED BACKGROUND AND AIM: Microbial dysbiosis is involved in the development of colorectal cancer and its most common precancerous lesion, colorectal adenoma. Endoscopic resection is one of the procedures for primary prevention of colorectal cancer, yet little is known about how the endoscopic therapy influences gut microbiota. METHODS We conducted a prospective study of 20 patients who underwent endoscopic resection of colorectal adenoma and analyzed the fecal microbiota before and 3 months after adenoma resection. MiSeq sequencing of 16S rRNA genes was performed to determine the alterations in microbial diversity and structure. To discriminate the microbiota of the two groups, random forest and receiver operating characteristic analysis were applied, and a genus-based microbiota signature was obtained. RESULTS Despite few alterations in overall microbial structure after adenoma resection, the abundance of Parabacteroides revealed a significant increase postoperatively (3.8% vs 1.5%, 0.1160), and the microbiota signature of Parabacteroides, Streptococcus, and Ruminococcus showed an optimal discriminating performance of postoperative status with the area under the curve 0.788, P < 0.001. CONCLUSION Fecal microbial alterations indicate the moderate influence of adenoma resection on gut microbiota and lay the groundwork for microbial prediction of adenoma recurrence. Larger sample studies are further required to validate the findings.
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Affiliation(s)
- Si-Yi Yu
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China
| | - Yuan-Hong Xie
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China
| | - Yi-Wen Qiu
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China
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Aarnoutse R, Ziemons J, Penders J, Rensen SS, de Vos-Geelen J, Smidt ML. The Clinical Link between Human Intestinal Microbiota and Systemic Cancer Therapy. Int J Mol Sci 2019; 20:E4145. [PMID: 31450659 PMCID: PMC6747354 DOI: 10.3390/ijms20174145] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 08/21/2019] [Accepted: 08/22/2019] [Indexed: 02/07/2023] Open
Abstract
Clinical interest in the human intestinal microbiota has increased considerably. However, an overview of clinical studies investigating the link between the human intestinal microbiota and systemic cancer therapy is lacking. This systematic review summarizes all clinical studies describing the association between baseline intestinal microbiota and systemic cancer therapy outcome as well as therapy-related changes in intestinal microbiota composition. A systematic literature search was performed and provided 23 articles. There were strong indications for a close association between the intestinal microbiota and outcome of immunotherapy. Furthermore, the development of chemotherapy-induced infectious complications seemed to be associated with the baseline microbiota profile. Both chemotherapy and immunotherapy induced drastic changes in gut microbiota composition with possible consequences for treatment efficacy. Evidence in the field of hormonal therapy was very limited. Large heterogeneity concerning study design, study population, and methods used for analysis limited comparability and generalization of results. For the future, longitudinal studies investigating the predictive ability of baseline intestinal microbiota concerning treatment outcome and complications as well as the potential use of microbiota-modulating strategies in cancer patients are required. More knowledge in this field is likely to be of clinical benefit since modulation of the microbiota might support cancer therapy in the future.
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Affiliation(s)
- Romy Aarnoutse
- GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands.
- Department of Surgery, Maastricht University Medical Center+, 6202 AZ Maastricht, The Netherlands.
| | - Janine Ziemons
- GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- Department of Surgery, Maastricht University Medical Center+, 6202 AZ Maastricht, The Netherlands
| | - John Penders
- Department of Medical Microbiology, Maastricht University Medical Center+, 6202 AZ Maastricht, The Netherlands
- NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
| | - Sander S Rensen
- Department of Surgery, Maastricht University Medical Center+, 6202 AZ Maastricht, The Netherlands
- NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
| | - Judith de Vos-Geelen
- GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- Department of Internal Medicine, Division of Medical Oncology, Maastricht University Medical Center+, 6202 AZ Maastricht, The Netherlands
| | - Marjolein L Smidt
- GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+, 6229 ER Maastricht, The Netherlands
- Department of Surgery, Maastricht University Medical Center+, 6202 AZ Maastricht, The Netherlands
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40
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Mori G, Orena BS, Cultrera I, Barbieri G, Albertini AM, Ranzani GN, Carnevali I, Tibiletti MG, Pasca MR. Gut Microbiota Analysis in Postoperative Lynch Syndrome Patients. Front Microbiol 2019; 10:1746. [PMID: 31417532 PMCID: PMC6682596 DOI: 10.3389/fmicb.2019.01746] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 07/15/2019] [Indexed: 01/02/2023] Open
Abstract
Lynch syndrome (LS) is a dominantly inherited condition with incomplete penetrance, characterized by high predisposition to colorectal cancer (CRC), endometrial and ovarian cancers, as well as to other tumors. LS is associated with constitutive DNA mismatch repair (MMR) gene defects, and carriers of the same pathogenic variants can show great phenotypic heterogeneity in terms of cancer spectrum. In the last years, human gut microbiota got a foothold among risk factors responsible for the onset and evolution of sporadic CRC, but its possible involvement in the modulation of LS patients’ phenotype still needs to be investigated. In this pilot study, we performed 16S rRNA gene sequencing of bacterial DNA extracted from fecal samples of 10 postoperative LS female patients who had developed colonic lesions (L-CRC) or gynecological cancers (L-GC). Our preliminary data show no differences between microbial communities of L-CRC and L-GC patients, but they plant the seed of the possible existence of a fecal microbiota pattern associated with LS genetic background, with Faecalibacterium prausnitzii, Parabacteroides distasonis, Ruminococcus bromii, Bacteroides plebeius, Bacteroides fragilis and Bacteroides uniformis species being the most significantly over-represented in LS patients (comprising both L-CRC and L-GC groups) compared to healthy subjects.
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Affiliation(s)
- Giorgia Mori
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy
| | - Beatrice Silvia Orena
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy
| | - Ilenia Cultrera
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy
| | - Giulia Barbieri
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy
| | - Alessandra M Albertini
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy
| | - Guglielmina Nadia Ranzani
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy.,Research Center for the Study of Hereditary and Familial Tumors, University of Insubria, Varese, Italy
| | - Ileana Carnevali
- Research Center for the Study of Hereditary and Familial Tumors, University of Insubria, Varese, Italy.,Department of Pathology, ASST-Sette Laghi, Varese, Italy
| | - Maria Grazia Tibiletti
- Research Center for the Study of Hereditary and Familial Tumors, University of Insubria, Varese, Italy.,Department of Pathology, ASST-Sette Laghi, Varese, Italy
| | - Maria Rosalia Pasca
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy
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Sze MA, Topçuoğlu BD, Lesniak NA, Ruffin MT, Schloss PD. Fecal Short-Chain Fatty Acids Are Not Predictive of Colonic Tumor Status and Cannot Be Predicted Based on Bacterial Community Structure. mBio 2019; 10:e01454-19. [PMID: 31266879 PMCID: PMC6606814 DOI: 10.1128/mbio.01454-19] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 06/07/2019] [Indexed: 01/11/2023] Open
Abstract
Colonic bacterial populations are thought to have a role in the development of colorectal cancer with some protecting against inflammation and others exacerbating inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory properties and are produced in large quantities by colonic bacteria that produce SCFAs by fermenting fiber. We assessed whether there was an association between fecal SCFA concentrations and the presence of colonic adenomas or carcinomas in a cohort of individuals using 16S rRNA gene and metagenomic shotgun sequence data. We measured the fecal concentrations of acetate, propionate, and butyrate within the cohort and found that there were no significant associations between SCFA concentration and tumor status. When we incorporated these concentrations into random forest classification models trained to differentiate between people with healthy colons and those with adenomas or carcinomas, we found that they did not significantly improve the ability of 16S rRNA gene or metagenomic gene sequence-based models to classify individuals. Finally, we generated random forest regression models trained to predict the concentration of each SCFA based on 16S rRNA gene or metagenomic gene sequence data from the same samples. These models performed poorly and were able to explain at most 14% of the observed variation in the SCFA concentrations. These results support the broader epidemiological data that questions the value of fiber consumption for reducing the risks of colorectal cancer. Although other bacterial metabolites may serve as biomarkers to detect adenomas or carcinomas, fecal SCFA concentrations have limited predictive power.IMPORTANCE Considering that colorectal cancer is the third leading cancer-related cause of death within the United States, it is important to detect colorectal tumors early and to prevent the formation of tumors. Short-chain fatty acids (SCFAs) are often used as a surrogate for measuring gut health and for being anticarcinogenic because of their anti-inflammatory properties. We evaluated the fecal SCFA concentrations of a cohort of individuals with different colonic tumor burdens who were previously analyzed to identify microbiome-based biomarkers of tumors. We were unable to find an association between SCFA concentration and tumor burden or use SCFAs to improve our microbiome-based models of classifying people based on their tumor status. Furthermore, we were unable to find an association between the fecal community structure and SCFA concentrations. Our results indicate that the association between fecal SCFAs, the gut microbiome, and tumor burden is weak.
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Affiliation(s)
- Marc A Sze
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Begüm D Topçuoğlu
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Nicholas A Lesniak
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Mack T Ruffin
- Department of Family Medicine and Community Medicine, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Patrick D Schloss
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
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Microbiota and gastrointestinal cancer. J Formos Med Assoc 2019; 118 Suppl 1:S32-S41. [PMID: 30655033 DOI: 10.1016/j.jfma.2019.01.002] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Accepted: 01/02/2019] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota plays important roles in many diseases, including cancer. It may promote carcinogenesis by inducing oxidative stress, genotoxicity, host immune response disturbance, and chronic inflammation. Colorectal cancer, hepatocellular carcinoma, and gastric cancer are the major gastrointestinal tract cancers in Taiwan. The microbiota detected in patients with tubular adenoma and villous/tubulovillous polyps is different from that in healthy controls and patients with hyperplastic polyps. Normalization of the microbiota is observed in patients after colorectal cancer treatment. Furthermore, the liver is exposed to microbiota-associated molecular patterns (MAMPs), bacterial metabolites, and toxins, as it is anatomically connected to the gut via the portal vein. Patients with cirrhosis have significantly higher plasma endotoxin levels than healthy controls. Helicobacter pylori is a well-established risk factor for gastric cancer. Some nitrosating bacteria convert nitrogen compounds in gastric fluid to potentially carcinogenic N-nitroso compounds, which also contribute to gastric cancer development. Growing evidence demonstrates that gut microbiota promotes carcinogenesis. In this review, we discuss the mechanisms and types of microbiota changes involved in these gastrointestinal cancers and the future treatment choices.
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Jin Y, Liu Y, Zhao L, Zhao F, Feng J, Li S, Chen H, Sun J, Zhu B, Geng R, Wei Y. Gut microbiota in patients after surgical treatment for colorectal cancer. Environ Microbiol 2018; 21:772-783. [PMID: 30548192 PMCID: PMC7379540 DOI: 10.1111/1462-2920.14498] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 11/30/2018] [Indexed: 01/05/2023]
Abstract
Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma‐carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non‐invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.
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Affiliation(s)
- Ye Jin
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Yang Liu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Lei Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Fuya Zhao
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Jing Feng
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Shengda Li
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Huinan Chen
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Jiayu Sun
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Biqiang Zhu
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Rui Geng
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
| | - Yunwei Wei
- Department of Oncological and Laparoscopic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China 150001
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Lam YF, Seto WK, Tong T, Cheung KS, Lo O, Hung IF, Law WL, Leung WK. Rates of metachronous adenoma after curative resection for left-sided or right-sided colon cancer. Intest Res 2018; 16:619-627. [PMID: 30301327 PMCID: PMC6223457 DOI: 10.5217/ir.2018.00013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 05/03/2018] [Indexed: 01/07/2023] Open
Abstract
Background/Aims We determined the rates of metachronous colorectal neoplasm in colorectal cancer (CRC) patients after resection for right (R)-sided or left (L)-sided cancer. Methods Consecutive CRC patients who had undergone surgical resection for curative intent in our hospital between 2001 and 2004 were identified. R-sided colonic cancers refer to cancer proximal to splenic flexure whereas L-sided cancers include rectal cancers. Patients were included only if they had a clearing colonoscopy performed either before or within 6 months after the operation. Findings of surveillance colonoscopy performed up to 5 years after colonic resection were included in the analysis. Results Eight hundred and sixty-three CRC patients underwent curative surgical resection during the study period. Three hundred and twenty-seven patients (107 R-sided and 220 L-sided) fulfilled the inclusion criteria and had at least 1 postoperative surveillance colonoscopy performed. The proportion of patients who had polyp and adenoma on surveillance colonoscopy was significantly higher among patients with L-sided than R-sided cancers (polyps: 30.9% vs. 19.6%, P=0.03; adenomas: 25.5% vs. 13.1%, P=0.01). The mean number of adenoma per patient on surveillance colonoscopy was also higher for patients with L-sided than R-sided tumors (0.52; 95% confidence interval [CI], 0.37–0.68 vs. 0.22; 95% CI, 0.08–0.35; P<0.01). Multivariate analysis showed that L-sided cancers, age, male gender and longer follow-up were independent predictors of adenoma detection on surveillance colonoscopy. Conclusions Patients with Lsided cancer had a higher rate of metachronous polyps and adenoma than those with R-sided cancer on surveillance colonoscopy.
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Affiliation(s)
- Yuk Fai Lam
- Department of Medicine Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Wai Kay Seto
- Department of Medicine Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Teresa Tong
- Department of Medicine Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Ka Shing Cheung
- Department of Medicine Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Oswens Lo
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Ivan Fn Hung
- Department of Medicine Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Wai Lun Law
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Wai K Leung
- Department of Medicine Queen Mary Hospital, The University of Hong Kong, Hong Kong
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Shifts of Faecal Microbiota During Sporadic Colorectal Carcinogenesis. Sci Rep 2018; 8:10329. [PMID: 29985435 PMCID: PMC6037773 DOI: 10.1038/s41598-018-28671-9] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 06/27/2018] [Indexed: 12/18/2022] Open
Abstract
Gut microbiota has been implicated in the etiopathogenesis of colorectal cancer. The development of colorectal cancer is a multistep process by which healthy epithelium slowly develops into preneoplastic lesions, which in turn progress into malignant carcinomas over time. In particular, sporadic colorectal cancers can arise from adenomas (about 85% of cases) or serrated polyps through the "adenoma-carcinoma" or the "serrated polyp-carcinoma" sequences, respectively. In this study, we performed 16 S rRNA gene sequencing of bacterial DNA extracted from faecal samples to compare the microbiota of healthy subjects and patients with different preneoplastic and neoplastic lesions. We identified putative microbial biomarkers associated with stage-specific progression of colorectal cancer. In particular, bacteria belonging to the Firmicutes and Actinobacteria phyla, as well as members of the Lachnospiraceae family, proved to be specific of the faecal microbiota of patients with preneoplastic lesions, including adenomas and hyperplastic polyps. On the other hand, two families of the Proteobacteria phylum, Alcaligeneaceae and Enterobacteriaceae, with Sutterella and Escherichia/Shigella being the most representative genera, appeared to be associated with malignancy. These findings, once confirmed on larger cohorts of patients, can represent an important step towards the development of more effective diagnostic strategies.
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Sze MA, Schloss PD. Leveraging Existing 16S rRNA Gene Surveys To Identify Reproducible Biomarkers in Individuals with Colorectal Tumors. mBio 2018; 9:e00630-18. [PMID: 29871916 PMCID: PMC5989068 DOI: 10.1128/mbio.00630-18] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 05/10/2018] [Indexed: 12/20/2022] Open
Abstract
An increasing body of literature suggests that both individual and collections of bacteria are associated with the progression of colorectal cancer. As the number of studies investigating these associations increases and the number of subjects in each study increases, a meta-analysis to identify the associations that are the most predictive of disease progression is warranted. We analyzed previously published 16S rRNA gene sequencing data collected from feces and colon tissue. We quantified the odds ratios (ORs) for individual bacterial taxa that were associated with an individual having tumors relative to a normal colon. Among the fecal samples, there were no taxa that had significant ORs associated with adenoma and there were 8 taxa with significant ORs associated with carcinoma. Similarly, among the tissue samples, there were no taxa that had a significant OR associated with adenoma and there were 3 taxa with significant ORs associated with carcinoma. Among the significant ORs, the association between individual taxa and tumor diagnosis was equal to or below 7.11. Because individual taxa had limited association with tumor diagnosis, we trained Random Forest classification models using only the taxa that had significant ORs, using the entire collection of taxa found in each study, and using operational taxonomic units defined based on a 97% similarity threshold. All training approaches yielded similar classification success as measured using the area under the curve. The ability to correctly classify individuals with adenomas was poor, and the ability to classify individuals with carcinomas was considerably better using sequences from feces or tissue.IMPORTANCE Colorectal cancer is a significant and growing health problem in which animal models and epidemiological data suggest that the colonic microbiota have a role in tumorigenesis. These observations indicate that the colonic microbiota is a reservoir of biomarkers that may improve our ability to detect colonic tumors using noninvasive approaches. This meta-analysis identifies and validates a set of 8 bacterial taxa that can be used within a Random Forest modeling framework to differentiate individuals as having normal colons or carcinomas. When models trained using one data set were tested on other data sets, the models performed well. These results lend support to the use of fecal biomarkers for the detection of tumors. Furthermore, these biomarkers are plausible candidates for further mechanistic studies into the role of the gut microbiota in tumorigenesis.
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Affiliation(s)
- Marc A Sze
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Patrick D Schloss
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
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