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Greco L, Rubbino F, Ferrari C, Cameletti M, Grizzi F, Bonelli F, Malesci A, Mazzone M, Ricciardiello L, Laghi L. Association of Fusobacterium nucleatum with colorectal cancer molecular subtypes and its outcome: a systematic review. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2025; 6:e5. [PMID: 40297307 PMCID: PMC12035788 DOI: 10.1017/gmb.2025.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 03/27/2025] [Accepted: 03/28/2025] [Indexed: 04/30/2025]
Abstract
Colorectal cancer (CRC) represents a relevant public health problem, with high incidence and mortality in Western countries. CRC can occur as sporadic (65%-75%), common familial (25%), or as a consequence of an inherited predisposition (up to 10%). While unravelling its genetic basis has been a long trip leading to relevant clinical implementation over more than 30 years, other contributing factors remain to be clarified. Among these, micro-organisms have emerged as critical players in the development and progression of the disease, as well as for CRC treatment response. Fusobacterium nucleatum (Fn) has been associated with CRC development in both pre-clinical models and clinical settings. Fusobacteria are core members of the human oral microbiome, while being less prevalent in the healthy gut, prompting questions about their localization in CRC and its precursor lesions. This review aims to critically discuss the evidence connecting Fn with CRC pathogenesis, its molecular subtypes and clinical outcomes.
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Affiliation(s)
- Luana Greco
- Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Federica Rubbino
- Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Clarissa Ferrari
- Research and Clinical Trials Office, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
| | | | - Fabio Grizzi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Milan, Italy
| | | | | | - Massimiliano Mazzone
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Macrophage Dynamics Lab, IRCCS Humanitas Research Hospital, Milan, Italy
- Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium
- Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium
| | - Luigi Ricciardiello
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas at MD Anderson Cancer Center, Houston, TX, USA
| | - Luigi Laghi
- Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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Sun J, Song S, Liu J, Chen F, Li X, Wu G. Gut microbiota as a new target for anticancer therapy: from mechanism to means of regulation. NPJ Biofilms Microbiomes 2025; 11:43. [PMID: 40069181 PMCID: PMC11897378 DOI: 10.1038/s41522-025-00678-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 03/04/2025] [Indexed: 03/15/2025] Open
Abstract
In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.
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Affiliation(s)
- Jiaao Sun
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shiyan Song
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiahua Liu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Feng Chen
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
| | - Xiaorui Li
- Department of oncology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
| | - Guangzhen Wu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
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Darnindro N, Abdullah M, Sukartini N, Rumende CM, Pitarini A, Nursyirwan SA, Fauzi A, Makmun D, Nelwan EJ, Shatri H, Rinaldi I, Tanadi C. Differences in diversity and composition of mucosa-associated colonic microbiota in colorectal cancer and non-colorectal cancer in Indonesia. World J Gastroenterol 2025; 31:100051. [PMID: 39991683 PMCID: PMC11755252 DOI: 10.3748/wjg.v31.i7.100051] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 12/05/2024] [Accepted: 12/23/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide. Several studies have shown an association between gut microbiota and colorectal cancer. Gut microbiota is unique and can be influenced by geographic factors and habits. This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer. AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia. METHODS This case-control study included 59 subjects (35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr. Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital. Microbiota examination was performed using 16S rRNA sequencing. Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs (Oxford Nanopore Technologies platform). RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index (3.28 vs 2.82, P > 0.05) and a lower value on the Simpson index (0.050 vs 0.060, P > 0.05). Significant differences in beta diversity were observed at the genus (P = 0.002) and species levels (P = 0.001). Firmicutes, Proteobacteria, Bacteroidetes, and Fusobacteria were the dominant phyla. The genera Bacteroides, Campylobacter, Peptostreptococcus, and Parvimonas were found more frequently in colorectal cancer, while Faecalibacterium, Haemophilus, and Phocaeicola were more frequently found in non-colorectal cancer. The relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Enterococcus faecalis, Campylobacter hominis, and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer. Meanwhile, Faecalibacterium prausnitzii, Faecalibacterium duncaniae, and Prevotella copri were more commonly found in non-colorectal cancer. CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer. This study was reviewed and approved by the Ethics Committee of Faculty of Medicine, Universitas Indonesia (No. KET-1517/UN2.F1/ETIK/PPM.00.02/2023).
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Affiliation(s)
- Nikko Darnindro
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
- Division of Gastrohepatology, Department of Internal Medicine, Fatmawati General Hospital, Jakarta 12430, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
- Human Cancer Research Center, IMERI Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
| | - Ninik Sukartini
- Department of Clinical Pathology, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Cleopas M Rumende
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Amanda Pitarini
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Saskia A Nursyirwan
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Achmad Fauzi
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Dadang Makmun
- Division of Gastroenterology, Pancreatobiliary and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Erni J Nelwan
- Division of Tropical Medicine and Infectious Disease, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Hamzah Shatri
- Division of Psychosomatic and Palliative Medicine, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Ikhwan Rinaldi
- Division of Haematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia-Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Caroline Tanadi
- School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta 14440, Indonesia
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Said SS, Ibrahim WN. Gut Microbiota-Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer. Cancer Manag Res 2025; 17:171-192. [PMID: 39881948 PMCID: PMC11776928 DOI: 10.2147/cmar.s405590] [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: 09/06/2024] [Accepted: 11/21/2024] [Indexed: 01/31/2025] Open
Abstract
Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade immune detection. Although ICIs have shown promising results, especially in solid tumors, patient responses vary widely due to multiple intrinsic and extrinsic factors within the tumor microenvironment. Emerging evidence suggests that the gut microbiota plays a pivotal role in modulating immune responses at the tumor site and may even influence treatment outcomes in cancer patients receiving ICIs. This review explores the complex interactions between the gut microbiota and the tumor microenvironment, examining how these interactions could impact the effectiveness of ICI therapy. Furthermore, we discuss how dysbiosis, an imbalance in gut microbiota composition, may contribute to resistance to ICIs, and highlight microbiota-targeted strategies to potentially overcome this challenge. Additionally, we review recent studies investigating the diagnostic potential of microbiota profiles in cancer patients, considering how microbial markers might aid in early detection and stratification of patient responses to ICIs. By integrating insights from recent preclinical and clinical studies, we aim to shed light on the potential of microbiome modulation as an adjunct to cancer immunotherapy and as a diagnostic tool, paving the way for personalized therapeutic approaches that optimize patient outcomes.
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Affiliation(s)
- Sawsan Sudqi Said
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - Wisam Nabeel Ibrahim
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
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Vicente-Valor J, Tesolato S, Paz-Cabezas M, Gómez-Garre D, Ortega-Hernández A, de la Serna S, Domínguez-Serrano I, Dziakova J, Rivera D, Jarabo JR, Gómez-Martínez AM, Hernando F, Torres A, Iniesta P. Fecal Microbiota Strongly Correlates with Tissue Microbiota Composition in Colorectal Cancer but Not in Non-Small Cell Lung Cancer. Int J Mol Sci 2025; 26:717. [PMID: 39859429 PMCID: PMC11766298 DOI: 10.3390/ijms26020717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/13/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree of correlation between the composition of the tissue microbiota and that of the feces of patients affected by CRC and NSCLC. Specifically, we investigated tumor and non-tumor tissues from 38 recruited patients with CRC and 19 with NSCLC. DNA from samples was submitted for 16S rDNA metagenomic sequencing, followed by data analysis through the QIIME2 pipeline and further statistical processing with STATA IC16. Tumor and non-tumor tissue selected genera were highly correlated in both CRC and NSCLC (100% and 81.25%). Following this, we established tissue-feces correlations, using selected genera from a LEfSe analysis previously published. In CRC, we found a strong correlation between the taxa detected in feces and those from colorectal tissues. However, our data do not demonstrate this correlation in NSCLC. In conclusion, our findings strongly reinforce the utility of fecal microbiota as a non-invasive biomarker for CRC diagnosis, while highlighting critical distinctions for NSCLC. Furthermore, our data demonstrate that the microbiota components of tumor and non-tumor tissues are similar, with only minor differences being detected.
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Affiliation(s)
- Juan Vicente-Valor
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, 28040 Madrid, Spain; (J.V.-V.); (S.T.)
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
| | - Sofía Tesolato
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, 28040 Madrid, Spain; (J.V.-V.); (S.T.)
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
| | - Mateo Paz-Cabezas
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Biomedical Research Networking Center in Cancer (CIBERONC), Carlos III Health Institute, 28029 Madrid, Spain
| | - Dulcenombre Gómez-Garre
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Cardiovascular Risk Group, Microbiota Laboratory, San Carlos Hospital, 28040 Madrid, Spain
- Department of Physiology, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
- Biomedical Research Networking Center in Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, 28029 Madrid, Spain
| | - Adriana Ortega-Hernández
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Cardiovascular Risk Group, Microbiota Laboratory, San Carlos Hospital, 28040 Madrid, Spain
| | - Sofía de la Serna
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Digestive Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
| | - Inmaculada Domínguez-Serrano
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Digestive Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
| | - Jana Dziakova
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Digestive Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
| | - Daniel Rivera
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Digestive Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
| | - Jose-Ramón Jarabo
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
- Thoracic Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
| | - Ana-María Gómez-Martínez
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
- Thoracic Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
| | - Florentino Hernando
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
- Thoracic Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
| | - Antonio Torres
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
- Digestive Surgery Service, San Carlos Hospital, 28040 Madrid, Spain
- Department of Surgery, Faculty of Medicine, Complutense University, 28040 Madrid, Spain
| | - Pilar Iniesta
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, 28040 Madrid, Spain; (J.V.-V.); (S.T.)
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain; (M.P.-C.); (D.G.-G.); (A.O.-H.); (S.d.l.S.); (I.D.-S.); (J.D.); (D.R.); (J.-R.J.); (A.-M.G.-M.); (F.H.); (A.T.)
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González A, Badiola I, Fullaondo A, Rodríguez J, Odriozola A. Personalised medicine based on host genetics and microbiota applied to colorectal cancer. ADVANCES IN GENETICS 2024; 112:411-485. [PMID: 39396842 DOI: 10.1016/bs.adgen.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) ranks second in incidence and third in cancer mortality worldwide. This situation, together with the understanding of the heterogeneity of the disease, has highlighted the need to develop a more individualised approach to its prevention, diagnosis and treatment through personalised medicine. This approach aims to stratify patients according to risk, predict disease progression and determine the most appropriate treatment. It is essential to identify patients who may respond adequately to treatment and those who may be resistant to treatment to avoid unnecessary therapies and minimise adverse side effects. Current research is focused on identifying biomarkers such as specific mutated genes, the type of mutations and molecular profiles critical for the individualisation of CRC diagnosis, prognosis and treatment guidance. In addition, the study of the intestinal microbiota as biomarkers is being incorporated due to the growing scientific evidence supporting its influence on this disease. This article comprehensively addresses the use of current and emerging diagnostic, prognostic and predictive biomarkers in precision medicine against CRC. The effects of host genetics and gut microbiota composition on new approaches to treating this disease are discussed. How the gut microbiota could mitigate the side effects of treatment is reviewed. In addition, strategies to modulate the gut microbiota, such as dietary interventions, antibiotics, and transplantation of faecal microbiota and phages, are discussed to improve CRC prevention and treatment. These findings provide a solid foundation for future research and improving the care of CRC patients.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Iker Badiola
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | | | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
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Du Y, Wang Q, Zheng Z, Zhou H, Han Y, Qi A, Jiao L, Gong Y. Gut microbiota influence on lung cancer risk through blood metabolite mediation: from a comprehensive Mendelian randomization analysis and genetic analysis. Front Nutr 2024; 11:1425802. [PMID: 39323566 PMCID: PMC11423778 DOI: 10.3389/fnut.2024.1425802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/26/2024] [Indexed: 09/27/2024] Open
Abstract
Background Gut microbiota (GM) and metabolic alterations play pivotal roles in lung cancer (LC) development and host genetic variations are known to contribute to LC susceptibility by modulating the GM. However, the causal links among GM, metabolite, host genes, and LC remain to be fully delineated. Method Through bidirectional MR analyses, we examined the causal links between GM and LC, and utilized two-step mediation analysis to identify potential mediating blood metabolite. We employed diverse MR methods, including inverse-variance-weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode, to ensure a robust examination of the data. MR-Egger intercept test, Radial MR, MR-PRESSO, Cochran Q test and Leave-one-out (LOO) analysis were used for sensitivity analyses. Analyses were adjusted for smoking, alcohol intake frequency and air pollution. Linkage disequilibrium score regression and Steiger test were used to probe genetic causality. The study also explored the association between specific host genes and the abundance of gut microbes in LC patients. Results The presence of Bacteroides clarus was associated with an increased risk of LC (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03-1.11, p = 0.012), whereas the Eubacteriaceae showed a protective effect (OR = 0.82, 95% CI: 0.75-0.89, p = 0.001). These findings remained robust after False Discovery Rate (FDR) correction. Our mediator screening identified 13 blood metabolites that significantly influence LC risk after FDR correction, underscoring cystine and propionylcarnitine in reducing LC risk, while linking specific lipids and hydroxy acids to an increased risk. Our two-step mediation analysis demonstrated that the association between the bacterial pathway of synthesis of guanosine ribonucleotides and LC was mediated by Fructosyllysine, with mediated proportions of 11.38% (p = 0.037). LDSC analysis confirmed the robustness of these associations. Our study unveiled significant host genes ROBO2 may influence the abundance of pathogenic gut microbes in LC patients. Metabolic pathway analysis revealed glutathione metabolism and glutamate metabolism are the pathways most enriched with significant metabolites related to LC. Conclusion These findings underscore the importance of GM in the development of LC, with metabolites partly mediating this effect, and provide dietary and lifestyle recommendations for high-risk lung cancer populations.
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Affiliation(s)
- Yizhao Du
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Qin Wang
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zongmei Zheng
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hailun Zhou
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yang Han
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ao Qi
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lijing Jiao
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Translational Cancer Research for Integrated Chinese and Western Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yabin Gong
- Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Fusco W, Bricca L, Kaitsas F, Tartaglia MF, Venturini I, Rugge M, Gasbarrini A, Cammarota G, Ianiro G. Gut microbiota in colorectal cancer: From pathogenesis to clinic. Best Pract Res Clin Gastroenterol 2024; 72:101941. [PMID: 39645279 DOI: 10.1016/j.bpg.2024.101941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 06/04/2024] [Indexed: 12/09/2024]
Abstract
Colorectal cancer is the third most common type of cancer, with a significant burden on healthcare and social systems. Its incidence is constantly rising, due to the spread of unhealthy lifestyle, i.e. Western diet. Increasing evidence suggests that westernization-driven microbiome alterations may play a critical role in colorectal tumorigenesis. The current screening strategies for this neoplasm, mainly fecal immunochemical tests, are burdened by unsatisfactory accuracy. Novel, non-invasive biomarkers are rising as the new frontier of colorectal cancer screening, and the microbiome-based ones are showing positive and optimistic results. This Review describes our current knowledge on the role of gut microbiota in colorectal cancer, from its pathogenetic action to its clinical potential as diagnostic biomarker.
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Affiliation(s)
- William Fusco
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy.
| | - Ludovica Bricca
- Department of Medicine - DIMED, Surgical Pathology and Cytopathology Unit, Università degli Studi di Padova, Padova, Italy
| | - Francesco Kaitsas
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Irene Venturini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Massimo Rugge
- Department of Medicine - DIMED, Surgical Pathology and Cytopathology Unit, Università degli Studi di Padova, Padova, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
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9
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Lopes SR, Martins C, Santos IC, Teixeira M, Gamito É, Alves AL. Colorectal cancer screening: A review of current knowledge and progress in research. World J Gastrointest Oncol 2024; 16:1119-1133. [PMID: 38660635 PMCID: PMC11037045 DOI: 10.4251/wjgo.v16.i4.1119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/16/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.
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Affiliation(s)
- Sara Ramos Lopes
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Claudio Martins
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Inês Costa Santos
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Madalena Teixeira
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Élia Gamito
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Ana Luisa Alves
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
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10
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Dai JH, Tan XR, Qiao H, Liu N. Emerging clinical relevance of microbiome in cancer: promising biomarkers and therapeutic targets. Protein Cell 2024; 15:239-260. [PMID: 37946397 PMCID: PMC10984626 DOI: 10.1093/procel/pwad052] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 10/22/2023] [Indexed: 11/12/2023] Open
Abstract
The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years, leading to numerous researches on cancer microbiome entering clinical evaluation. As promising biomarkers and therapeutic targets, the critical involvement of microbiota in cancer clinical practice has been increasingly appreciated. Here, recent progress in this field is reviewed. We describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers, respectively. In addition, we highlight the relationship between microbiota and the therapeutic efficacy, toxicity, or side effects of commonly utilized treatments for cancer, including chemotherapy, radiotherapy, and immunotherapy. Given that microbial factors influence the cancer treatment outcome, we further summarize some dominating microbial interventions and discuss the hidden risks of these strategies. This review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.
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Affiliation(s)
- Jia-Hao Dai
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China
| | - Xi-Rong Tan
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China
| | - Han Qiao
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China
| | - Na Liu
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China
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11
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Liu Q, Yang Y, Pan M, Yang F, Yu Y, Qian Z. Role of the gut microbiota in tumorigenesis and treatment. Theranostics 2024; 14:2304-2328. [PMID: 38646653 PMCID: PMC11024857 DOI: 10.7150/thno.91700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 03/01/2024] [Indexed: 04/23/2024] Open
Abstract
The gut microbiota is a crucial component of the intricate microecosystem within the human body that engages in interactions with the host and influences various physiological processes and pathological conditions. In recent years, the association between dysbiosis of the gut microbiota and tumorigenesis has garnered increasing attention, as it is recognized as a hallmark of cancer within the scientific community. However, only a few microorganisms have been identified as potential drivers of tumorigenesis, and enhancing the molecular understanding of this process has substantial scientific importance and clinical relevance for cancer treatment. In this review, we delineate the impact of the gut microbiota on tumorigenesis and treatment in multiple types of cancer while also analyzing the associated molecular mechanisms. Moreover, we discuss the utility of gut microbiota data in cancer diagnosis and patient stratification. We further outline current research on harnessing microorganisms for cancer treatment while also analyzing the prospects and challenges associated with this approach.
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Affiliation(s)
- Qingya Liu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yun Yang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Meng Pan
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Fan Yang
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yan Yu
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhiyong Qian
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
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12
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Cassana A, Abedrapo M, Diaz M, Zamorano D, Zárate A. Tamizaje de cáncer colorrectal: pruebas emergentes no invasivas. REVISTA MÉDICA CLÍNICA LAS CONDES 2024; 35:82-87. [DOI: 10.1016/j.rmclc.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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13
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Tesolato S, Ortega-Hernández A, Gómez-Garre D, Claver P, De Juan C, De la Serna S, Paz M, Domínguez-Serrano I, Dziakova J, Rivera D, Torres A, Iniesta P. Gut microbiota profiles in feces and paired tumor and non-tumor tissues from Colorectal Cancer patients. Relationship to the Body Mass Index. PLoS One 2023; 18:e0292551. [PMID: 37796924 PMCID: PMC10553240 DOI: 10.1371/journal.pone.0292551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 09/25/2023] [Indexed: 10/07/2023] Open
Abstract
Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC.
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Affiliation(s)
- Sofía Tesolato
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, Madrid, Spain
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
| | - Adriana Ortega-Hernández
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Cardiovascular Risk Group and Microbiota Laboratory, San Carlos Hospital, Madrid, Spain
| | - Dulcenombre Gómez-Garre
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Cardiovascular Risk Group and Microbiota Laboratory, San Carlos Hospital, Madrid, Spain
- Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain
- Biomedical Research Networking Center in Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
| | - Paula Claver
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, Madrid, Spain
| | - Carmen De Juan
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, Madrid, Spain
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
| | - Sofía De la Serna
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Digestive Surgery Service, San Carlos Hospital, Madrid, Spain
| | - Mateo Paz
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Biomedical Research Networking Center in Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
| | - Inmaculada Domínguez-Serrano
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Digestive Surgery Service, San Carlos Hospital, Madrid, Spain
| | - Jana Dziakova
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Digestive Surgery Service, San Carlos Hospital, Madrid, Spain
| | - Daniel Rivera
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Digestive Surgery Service, San Carlos Hospital, Madrid, Spain
| | - Antonio Torres
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
- Digestive Surgery Service, San Carlos Hospital, Madrid, Spain
| | - Pilar Iniesta
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, Madrid, Spain
- San Carlos Health Research Institute (IdISSC), Madrid, Spain
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14
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Chen Q, Wang L, Song H, Xing W, Shi J, Li Y, Wang Z, Chen J, Xie N, Zhao W. Deficiency of SR-B1 reduced the tumor load of colitis-induced or APC min /+ -induced colorectal cancer. Cancer Med 2023; 12:19744-19757. [PMID: 37766594 PMCID: PMC10587988 DOI: 10.1002/cam4.6534] [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: 05/25/2023] [Revised: 08/03/2023] [Accepted: 09/01/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR-B1), a multi-ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR-B1 in CRC development has not been reported. AIMS This study aimed to clarify the importance of SR-B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. MATERIALS & METHODS In this study, we used SR-B1 gene knockdown mice to study the effect of SR-B1 on colitis-induced or APCmin/+ -induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin-eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high-throughput sequencing. RESULTS The results showed that SR-B1 knockdown reduced the tumor load of colitis-induced or APCmin/+ -induced CRC. SR-B1 knockdown improved the immune microenvironment by affecting the level of tumor-associated macrophage (TAM), mononuclear myeloid-derived suppressor cells (M-MDSCs), granulocytic myeloid-derived suppressor cells (G-MDSCs), programmed cell death-ligand 1 (PD-L1), and human leukocyte antigen class I-B (HLA-B), and also reduced the level of low-density lipoprotein receptor (LDL-R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR-B1 knockdown can also trigger the anti-CRC effect of anti-PD 1 in colitis-induced CRC. DISCUSSION SR-B1 deficiency significantly improved the immunity in tumor microenvironment of colitis-induced or APCmin/+ -induced CRC. In addition, the microbiota changes caused by SR-B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti-PD1 therapy. The mechanism of action of SR-B1 deficiency on the development of CRC still needs further in-depth research. CONCLUSION This study provides a new treatment strategy for treating CRC by affecting the expression of SR-B1 in intestine.
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Affiliation(s)
- Qijun Chen
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Lixue Wang
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Hui Song
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Wen Xing
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Junfeng Shi
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Yudi Li
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Ziqian Wang
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Jinlong Chen
- School of Basic Medical SciencesCapital Medical UniversityBeijingChina
| | - Nan Xie
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
| | - Wenhua Zhao
- School of Pharmaceutical SciencesCapital Medical UniversityBeijingChina
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15
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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] [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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16
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JIANG Y, ZHOU X, PU W, ZHOU C. Sanwu Baisan decoction inhibits colorectal cancer progression in mice by remodeling gut microbiota and tumorigenesis. J TRADIT CHIN MED 2023; 43:466-473. [PMID: 37147747 PMCID: PMC10133941 DOI: 10.19852/j.cnki.jtcm.20230214.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 05/25/2022] [Indexed: 05/07/2023]
Abstract
OBJECTIVE To uncover the anti-tumor effects and potential mechanism of Sanwu Baisan Decoction (, SWB) in treatment of colorectal cancer (CRC) in mice. METHODS Therapeutic effect was evaluated based on body weight gain, tumor volume, tumor growth inhibition rate, and histological changes and apoptosis in the tumor tissues. Anti-tumor immunity was studied by measuring plasma levels of anti-tumor cytokines, interleukin 6 (IL-6), interleukin 17 (IL-17), and interferon γ (IFN-γ). Gut morphological changes were evaluated by histological staining and tight junction proteins expressions. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Classical toll-like receptor 4 (TLR-4)/ cyclooxygenase 2 (COX-2)/ prostaglandin E2 (PGE-2) pathway was examined in colon tissue and tumor samples. RESULTS SWB presented high anti-tumor efficacy of CRC in mice, which manifested as decreased tumor volume and increased tumor growth inhibition rate. This anti-tumor effect of SWB was associated with elevated plasma levels of anti-tumor immune cytokines (IL-6, IL-17, and IFN-γ). Further studies showed that SWB also increases the expression of occluding and promotes the abundance of gut probiotics, , , and . Moreover, results suggested that the anti-tumor effects of SWB might associate with inducing cancer cell apoptosis and inhibiting the TLR-4/COX-2/PGE-2 pathway in both colon tissue and tumor samples. CONCLUSION SWB shows strong anti-tumor efficiency in mice with colorectal carcinoma, possibly through promoting the secretion of anti-tumor immune cytokines, inducing cancer apoptosis, maintaining the gut microbiota, and inhibiting tumorigenesis by inhibiting the TLR-4/COX-2/PGE-2 pathway.
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Affiliation(s)
- Yiqian JIANG
- 1 Department of Febrile Disease, Basic Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Xibin ZHOU
- 1 Department of Febrile Disease, Basic Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046, China
- 2 Department of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, China
| | - Wenyuan PU
- 1 Department of Febrile Disease, Basic Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Chunxiang ZHOU
- 1 Department of Febrile Disease, Basic Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046, China
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17
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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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18
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Lui RN, Wong SH, Ding NS, Sekiguchi M, Yu J, Ang TL, Yeoh KG, Chiu HM, Sung JJY. Is this the end of colonoscopy screening for colorectal cancer? An Asia-Pacific perspective. J Gastroenterol Hepatol 2023; 38:671-677. [PMID: 36987587 DOI: 10.1111/jgh.16182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 03/11/2023] [Accepted: 03/13/2023] [Indexed: 03/30/2023]
Affiliation(s)
- Rashid N Lui
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Sunny H Wong
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Nik Sheng Ding
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Masau Sekiguchi
- Cancer Screening Center/Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
- Division of Screening Technology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Jun Yu
- Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SAR, China
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Tiing-Leong Ang
- Changi General Hospital, SingHealth Group, Singapore, Singapore
| | - Khay-Guan Yeoh
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Joseph J Y Sung
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
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19
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Hanna M, Dey N, Grady WM. Emerging Tests for Noninvasive Colorectal Cancer Screening. Clin Gastroenterol Hepatol 2023; 21:604-616. [PMID: 36539002 PMCID: PMC9974876 DOI: 10.1016/j.cgh.2022.12.008] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 12/05/2022] [Accepted: 12/12/2022] [Indexed: 12/30/2022]
Abstract
Colorectal cancer (CRC) is among the most common cancers globally and a major cause of cancer-related deaths. The American Cancer Society estimates that CRC will kill 1 in 60 Americans, and CRC screening is recommended for all Americans ≥45 years of age. Current CRC screening methods are effective for preventing CRC and have been shown to reduce CRC-related mortality. However, none of the currently available tests is ideal, and many people are not compliant with screening recommendations. Novel screening tests based on advances in CRC molecular biology, genetics, and epigenetics, combined with developments in sequencing technologies and computational analytic methods, have been developed to address the shortcomings of current CRC screening tests. These emerging tests include blood-based assays that use plasma-derived circulating tumor DNA and serum proteins to detect early CRC and advanced adenomas, assays that use stool DNA or mRNA, and methods for profiling the gut microbiome. Here we review current screening modalities, and we discuss the principles behind the most promising emerging CRC screening tests and the data supporting their potential to be used in clinical practice.
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Affiliation(s)
- Marina Hanna
- Department of Medicine, University of Washington, Seattle, Washington
| | - Neelendu Dey
- Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington; Microbiome Research Initiative, Fred Hutchinson Cancer Center, Seattle, Washington.
| | - William M Grady
- Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.
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20
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Wong MCS, Huang J, Wong YY, Ko S, Chan VCW, Ng SC, Chan FKL. The Use of a Non-Invasive Biomarker for Colorectal Cancer Screening: A Comparative Cost-Effectiveness Modeling Study. Cancers (Basel) 2023; 15:cancers15030633. [PMID: 36765591 PMCID: PMC9913459 DOI: 10.3390/cancers15030633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 biomarker yearly, or colonoscopy every 10 years until the age of 75 years. Participants with positive FOBT or a result of "high risk" identified using the M3 biomarker are offered colonoscopy. We assumed surveillance colonoscopy is repeated every 3 years, and examined the treatment cost. A comparison of various outcome measures was conducted using Markov modelling. The incremental cost-effectiveness ratio (ICER) of FIT, M3 biomarker, and colonoscopy was USD108,176, USD133,485 and USD159,596, respectively. Comparing with FIT, the use of M3 biomarker could lead to significantly smaller total loss of cancer-related life-years (2783 vs. 5279); a higher number of CRC cases prevented (1622 vs. 146), a higher proportion of CRC cases prevented (50.2% vs. 4.5%), more life-years saved (2852 vs. 339), and cheaper total costs per life-year saved (USD212,553 vs. 773,894). The total costs per life-year saved is more affordable than that achieved by colonoscopy as a primary screening tool (USD212,553 vs. USD236,909). The findings show that M3 biomarkers may be more cost-effective than colonoscopy.
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Affiliation(s)
- Martin C. S. Wong
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Junjie Huang
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yuet-Yan Wong
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Samantha Ko
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Victor C. W. Chan
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Siew C. Ng
- Centre for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- The Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- Correspondence: (S.C.N.); (F.K.L.C.); Tel.: +852-3505-1339 (F.K.L.C.); Fax: +852-2647-1557 (F.K.L.C.)
| | - Francis K. L. Chan
- Centre for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
- The Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- Correspondence: (S.C.N.); (F.K.L.C.); Tel.: +852-3505-1339 (F.K.L.C.); Fax: +852-2647-1557 (F.K.L.C.)
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21
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Wang L, Yu KC, Hou YQ, Guo M, Yao F, Chen ZX. Gut microbiome in tumorigenesis and therapy of colorectal cancer. J Cell Physiol 2023; 238:94-108. [PMID: 36409765 DOI: 10.1002/jcp.30917] [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: 08/02/2022] [Revised: 11/09/2022] [Accepted: 11/09/2022] [Indexed: 11/22/2022]
Abstract
Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host-microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.
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Affiliation(s)
- Ling Wang
- Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, People's Republic of China
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
- Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, People's Republic of China
| | - Ke-Chun Yu
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Yun-Qing Hou
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Min Guo
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Fan Yao
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Zhen-Xia Chen
- Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, People's Republic of China
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
- Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, People's Republic of China
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22
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Zwezerijnen-Jiwa FH, Sivov H, Paizs P, Zafeiropoulou K, Kinross J. A systematic review of microbiome-derived biomarkers for early colorectal cancer detection. Neoplasia 2022; 36:100868. [PMID: 36566591 PMCID: PMC9804137 DOI: 10.1016/j.neo.2022.100868] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/24/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Increasing evidence suggests a role of the gut microbiome in the development of colorectal cancer (CRC) and that it can serve as a biomarker for early diagnosis. This review aims to give an overview of the current status of published studies regarding the microbiome as a screening tool for early CRC detection. A literature search was conducted using PubMed and EMBASE in August 2022. Studies assessing the efficacy of microbiome-derived biomarkers based on noninvasive derived samples were included. Not relevant studies or studies not specifying the stage of CRC or grouping them together in the analysis were excluded. The risk of bias for screening tools was performed using the QUADAS-2 checklist. A total of 28 studies were included, ranging from 2 to 462 for CRC and 18 to 665 advanced adenoma patient inclusions, of which only two investigated the co-metabolome as biomarker. The diagnostic performance of faecal bacteria-derived biomarkers had an AUC ranging from 0.28-0.98 for precursor lesions such as advanced adenomas and 0.54-0.89 for early CRC. Diagnostic performance based on the co-metabolome showed an AUC ranging from 0.69 - 0.84 for precursor lesions and 0.65 - 0.93 for early CRC. All models improved when combined with established clinical early detection markers such as gFOBT. A high level of heterogeneity was seen in the number of inclusions and methodology used in the studies. The faecal and oral gut microbiome has the potential to complement existing CRC screening tools, however current evidence suggests that this is not yet ready for routine clinical use.
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Affiliation(s)
- Florine H. Zwezerijnen-Jiwa
- Department of Surgery and Cancer, St. Mary's Hospital, Imperial College London, London W2 1NY, UK,Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, 1105 BK Amsterdam, The Netherlands,Department of Gastroenterology, Amsterdam University Medical Centres, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Hugo Sivov
- Department of Surgery and Cancer, St. Mary's Hospital, Imperial College London, London W2 1NY, UK
| | - Petra Paizs
- Department of Surgery and Cancer, St. Mary's Hospital, Imperial College London, London W2 1NY, UK
| | - Konstantina Zafeiropoulou
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, 1105 BK Amsterdam, The Netherlands,Department of Paediatric Surgery, Emma Children's Hospital, Amsterdam University Medical Centres, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - James Kinross
- Department of Surgery and Cancer, St. Mary's Hospital, Imperial College London, London W2 1NY, UK,Corresponding author at: Department of Surgery and Cancer, St. Mary's Hospital, Imperial College London, 10th Floor QEQMW, Praed Street, London, W2 1NY, UK
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23
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Zhang H, Yu Y, Li J, Gong P, Wang X, Li X, Cheng Y, Yu X, Zhang N, Zhang X. Changes of gut microbiota in colorectal cancer patients with Pentatrichomonas hominis infection. Front Cell Infect Microbiol 2022; 12:961974. [PMID: 36118043 PMCID: PMC9471007 DOI: 10.3389/fcimb.2022.961974] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 07/27/2022] [Indexed: 01/11/2023] Open
Abstract
Pentatrichomonas hominis is a parasitic trichomonads protozoa that parasitizes in the colon and cecum of humans and other animals. Our previous studies have demonstrated that infection with P. hominis is associated with the incidence of colon cancer (37.93%). However, the mechanism by which P. hominis infections increase the incidence of colon cancer remains unclear. Previous studies have suggested that certain parasites promote colon cancer by regulating gut microbiota. This study aimed to elucidate whether the association between P. hominis infections and the increased incidence of colon cancer is related to changes in gut microbiota. Therefore, the gut microbiota patients with colon cancer who were infected with P. hominis and uninfected patients with colon cancer were analyzed by 16S rRNA high-throughput sequencing. The results demonstrated that patients with colon cancer who were not infected with P. hominis showed increased gut bacterial diversity, a higher relative abundance of Alcaligenes sp., Leucobacter sp., Paraprevotella sp., Ruminococcaceae UCG-002, and a significant reduction in the abundance of Veillonella sp., compared to individuals without colon cancer. Additionally, the relative abundance of the Ruminococcaceae UCG-002 and the Eubacterium eligens groups was reduced, while the relative abundance of bacteria associated with colon cancer, including Flavonifractor sp., Lachnoclostridium sp., and the Ruminococcus gnavus group, increased significantly in patients with colon cancer who were infected with P. hominis, compared to those of uninfected patients with colon cancer. In conclusion, these results suggested that P. hominis infections may aggravate the development of colon cancer and the findings provide new insights for subsequent in-depth studies on the pathogenesis, diagnosis, and prevention of colon cancer.
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Affiliation(s)
- Hongbo Zhang
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yanhui Yu
- Second Affiliated Hospital, Jilin University, Changchun, China
| | - Jianhua Li
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Pengtao Gong
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiaocen Wang
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xin Li
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yidan Cheng
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiuyan Yu
- Clinical Laboratory, Jilin Cancer Hospital, Changchun, China
| | - Nan Zhang
- Key Laboratory of Zoonosis Research by Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China
- *Correspondence: Nan Zhang, ; Xichen Zhang,
| | - Xichen Zhang
- Key Laboratory of Zoonosis Research by Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
- *Correspondence: Nan Zhang, ; Xichen Zhang,
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24
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Aitchison A, Pearson JF, Purcell RV, Frizelle FA, Keenan JI. Detection of Fusobacterium nucleatum DNA in primary care patient stool samples does not predict progression of colorectal neoplasia. PLoS One 2022; 17:e0269541. [PMID: 35658028 PMCID: PMC9165787 DOI: 10.1371/journal.pone.0269541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 05/23/2022] [Indexed: 11/20/2022] Open
Abstract
Background Carriage of certain bacterial species may represent potential biomarkers of colorectal cancer (CRC). Prominent among these is Fusobacterium nucleatum. We explored the association of F. nucleatum DNA in stool samples with the presence of colonic neoplastic lesions in a cohort of primary care patients, and compared our findings with those from an unrelated cohort of colonoscopy patients followed clinically over time. Methods Carriage rates of F. nucleatum in stool samples were assessed in 185 patients referred for a faecal immunochemical test (FIT) by their general practitioners (GPs). Comparisons were made with stool samples from 57 patients diagnosed with CRC and 57 age-matched healthy controls, and with tissue samples taken at colonoscopy from 150 patients with a decade of subsequent clinical follow-up. Findings F. nucleatum DNA was found at a high rate (47.0%) in stool samples from primary care patients, and more often in stool samples from CRC patients (47.4%) than in healthy controls (7.0%), (P = 7.66E-7). No association was found between carriage of F. nucleatum and FIT positivity (P = 0.588). While evidence of stool-associated F. nucleatum DNA was significantly more likely to indicate a lesion in those primary care patients progressed to colonoscopy (P = 0.023), this finding did not extend to the progression of neoplastic lesions in the 150 patients with a decade of follow up. Conclusion The finding of F. nucleatum DNA at similar rates in stool samples from patients diagnosed with CRC and in primary care patients with pre-cancerous lesions supports growing awareness that the presence of these bacteria may be a biomarker for increased risk of disease. However, molecular evidence of F. nucleatum did not predict progression of colonic lesions, which may lessen the utility of this bacterium as a biomarker for increased risk of disease.
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Affiliation(s)
- Alan Aitchison
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - John F. Pearson
- Biostatistics and Computational Biology Unit, University of Otago Christchurch, Christchurch, New Zealand
| | - Rachel V. Purcell
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Frank A. Frizelle
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Jacqueline I. Keenan
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
- * E-mail:
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25
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Zhang X, Zhang Y, Gui X, Zhang Y, Zhang Z, Chen W, Zhang X, Wang Y, Zhang M, Shang Z, Xin Y, Zhang Y. Salivary Fusobacterium nucleatum serves as a potential biomarker for colorectal cancer. iScience 2022; 25:104203. [PMID: 35479401 PMCID: PMC9035728 DOI: 10.1016/j.isci.2022.104203] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 02/14/2022] [Accepted: 04/01/2022] [Indexed: 12/24/2022] Open
Abstract
Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.
Fusobacterium nucleatum DNA level is increased in saliva of colorectal cancer patients Salivary F. nucleatum DNA is a biomarker for colorectal cancer diagnosis Salivary F. nucleatum DNA is an independent prognostic factor KEGG identified relationships to ECM-receptor interaction and focal adhesion pathways
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26
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Abstract
INTRODUCTION Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. Nonetheless, with early detection of CRC or its precancerous lesions, mortality, and CRC incidence can be reduced. Although colonoscopy is currently the gold standard for CRC screening and diagnosis, its invasive nature, and troublesome bowel preparation deter patient participation. Therefore, there is a need to expand the use of noninvasive or minimally invasive methods to increase patient compliance. AREAS COVERED This review summarizes advances in different methods for CRC screening, including stool bacterial and metagenomic markers, fecal proteins, genetic and epigenetic markers in blood and stools, and imaging modalities. The cost-effectiveness of these methods is also discussed. FIT is more cost-effective compared to virtual colonoscopy, mSEPT9 test, and Multitarget Stool DNA test, while the cost-effectiveness of other noninvasive methods requires further evaluation. EXPERT OPINION Recent evidence has well demonstrated the usefulness of gut microbiome and certain fecal bacterial markers in the noninvasive diagnosis of CRC and its precancerous lesions. Many of the fecal biomarkers, from host cells or the gut environment, show better diagnostic sensitivity than FIT. New screening tests based on these fecal biomarkers can be expected to replace FIT with higher cost-effectiveness in the near future.
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Affiliation(s)
- Sarah Cheuk Hei Chan
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Jessie Qiaoyi Liang
- Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Cuhk Shenzhen Research Institute, the Chinese University of Hong Kong, Shatin, Hong Kong, China
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27
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Liang JQ, Zeng Y, Kwok G, Cheung CP, Suen BY, Ching JYL, To KF, Yu J, Chan FKL, Ng SC. Novel microbiome signatures for non-invasive diagnosis of adenoma recurrence after colonoscopic polypectomy. Aliment Pharmacol Ther 2022; 55:847-855. [PMID: 35224756 PMCID: PMC9303256 DOI: 10.1111/apt.16799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 09/14/2021] [Accepted: 01/17/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND We previously reported a panel of novel faecal microbiome gene markers for diagnosis of colorectal adenoma and cancer. AIM To evaluate whether these markers are useful in detecting adenoma recurrence after polypectomy. METHODS Subjects were enrolled in a polyp surveillance study from 2009 to 2019. Stool samples were collected before bowel preparation of index colonoscopy (baseline) and surveillance colonoscopy (follow-up). Fusobacterium nucleatum (Fn), Lachnoclostridium marker (m3), Clostridium hathewayi (Ch) and Bacteroides clarus were quantified in baseline and follow-up samples by quantitative polymerase chain reaction (qPCR) to correlate with adenoma recurrence. Recurrence was defined as new adenomas detected >6 months after polypectomy. Faecal immunochemical test (FIT) was performed for comparison. RESULTS A total of 161 baseline and 104 follow-up samples were analysed. Among patients with adenoma recurrence, Fn and m3 increased (both P < 0.05) while Ch were unchanged in follow-up versus baseline samples. Among patients without recurrence, Fn and m3 were unchanged while Ch decreased (P < 0.05) in follow-up versus baseline samples. Logistic regression that included changes of m3, Fn and Ch at follow-up compared with baseline achieved an area under receiver operating characteristic curve (AUROC) of 0.95 (95%CI: 0.84-0.99) with 90.0% sensitivity and 87.0% specificity for detecting recurrent adenoma. Combination of m3, Fn and Ch at follow-up sample achieved AUROC of 0.74 (95%CI: 0.65-0.82) with 81.3% sensitivity and 55.4% specificity for detecting recurrent adenoma. FIT showed limited sensitivity (8.3%) in detecting recurrent adenomas. CONCLUSION Our combinations of faecal microbiome gene markers can be potentially useful non-invasive tools for detecting adenoma recurrence.
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Affiliation(s)
- Jessie Qiaoyi Liang
- Department of Microbiology, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Centre for Gut Microbiota Research, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina,Microbiota I‐Centre (MagIC) LimitedThe Chinese University of Hong KongHong KongChina
| | - Yao Zeng
- Department of Microbiology, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Centre for Gut Microbiota Research, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Microbiota I‐Centre (MagIC) LimitedThe Chinese University of Hong KongHong KongChina
| | - Grace Kwok
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina
| | - Chun Pan Cheung
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Centre for Gut Microbiota Research, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina,Microbiota I‐Centre (MagIC) LimitedThe Chinese University of Hong KongHong KongChina
| | - Bing Yee Suen
- Department of SurgeryThe Chinese University of Hong KongHong KongChina
| | - Jessica Y. L. Ching
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina,Microbiota I‐Centre (MagIC) LimitedThe Chinese University of Hong KongHong KongChina
| | - Ka Fai To
- Department of Anatomy Chemical PathologyThe Chinese University of Hong KongHong KongChina
| | - Jun Yu
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Centre for Gut Microbiota Research, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina
| | - Francis K. L. Chan
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Centre for Gut Microbiota Research, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina,Microbiota I‐Centre (MagIC) LimitedThe Chinese University of Hong KongHong KongChina
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Centre for Gut Microbiota Research, Faculty of MedicineThe Chinese University of Hong KongHong KongChina,Institute of Digestive Disease, State Key Laboratory for Digestive Disease, Li Ka Shing Institute of Health Science, CUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina,Microbiota I‐Centre (MagIC) LimitedThe Chinese University of Hong KongHong KongChina
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28
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Zhou P, Yang D, Sun D, Zhou Y. Gut microbiome: New biomarkers in early screening of colorectal cancer. J Clin Lab Anal 2022; 36:e24359. [PMID: 35312122 PMCID: PMC9102648 DOI: 10.1002/jcla.24359] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Peng Zhou
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology School of Medicine Ningbo University Ningbo China
- Department of Gastroenterology The Affiliated Hospital of Medical School Ningbo University Ningbo China
| | - Dongxue Yang
- Department of Gastroenterology The Affiliated Hospital of Medical School Ningbo University Ningbo China
- Institute of Digestive Disease of Ningbo University Ningbo China
| | - Desen Sun
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology School of Medicine Ningbo University Ningbo China
- Department of Gastroenterology The Affiliated Hospital of Medical School Ningbo University Ningbo China
- Institute of Digestive Disease of Ningbo University Ningbo China
| | - Yuping Zhou
- Department of Gastroenterology The Affiliated Hospital of Medical School Ningbo University Ningbo China
- Institute of Digestive Disease of Ningbo University Ningbo China
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Duijster JW, Franz E, Neefjes J, Mughini-Gras L. Bacterial and Parasitic Pathogens as Risk Factors for Cancers in the Gastrointestinal Tract: A Review of Current Epidemiological Knowledge. Front Microbiol 2021; 12:790256. [PMID: 34956157 PMCID: PMC8692736 DOI: 10.3389/fmicb.2021.790256] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships.
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Affiliation(s)
- Janneke W. Duijster
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Eelco Franz
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Jacques Neefjes
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Lapo Mughini-Gras
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
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Identification of mucin degraders of the human gut microbiota. Sci Rep 2021; 11:11094. [PMID: 34045537 PMCID: PMC8159939 DOI: 10.1038/s41598-021-90553-4] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 05/07/2021] [Indexed: 12/22/2022] Open
Abstract
Mucins are large glycoproteins consisting of approximately 80% of hetero-oligosaccharides. Gut mucin degraders of healthy subjects were investigated, through a culture dependent and independent approach. The faeces of five healthy adults were subjected to three steps of anaerobic enrichment in a medium with sole mucins as carbon and nitrogen sources. The bacterial community was compared before and after the enrichment by 16S rRNA gene profiling. Bacteria capable of fermenting sugars, such as Anaerotruncus, Holdemania, and Enterococcaceae likely took advantage of the carbohydrate chains. Escherichia coli and Enterobacteriaceae, Peptococcales, the Coriobacteriale Eggerthella, and a variety of Clostridia such as Oscillospiraceae, Anaerotruncus, and Lachnoclostridium, significantly increased and likely participated to the degradation of the protein backbone of mucin. The affinity of E. coli and Enterobacteriaceae for mucin may facilitate the access to the gut mucosa, promoting gut barrier damage and triggering systemic inflammatory responses. Only three species of strict anaerobes able to grow on mucin were isolated from the enrichments of five different microbiota: Clostridium disporicum, Clostridium tertium, and Paraclostridium benzoelyticum. The limited number of species isolated confirms that in the gut the degradation of these glycoproteins results from cooperation and cross-feeding among several species exhibiting different metabolic capabilities.
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