|
1
|
Yin LL, Qi PQ, Hu YF, Fu XJ, He RS, Wang MM, Deng YJ, Xiong SY, Yu QW, Hu JP, Zhou L, Zhou ZB, Xiong Y, Deng H. Dysbiosis promotes recurrence of adenomatous polyps in the distal colorectum. World J Gastrointest Oncol 2024; 16:3600-3623. [PMID: 39171160 PMCID: PMC11334022 DOI: 10.4251/wjgo.v16.i8.3600] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/19/2024] [Accepted: 06/14/2024] [Indexed: 08/07/2024] Open
Abstract
BACKGROUND Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled. AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps. METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators. RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones. CONCLUSION These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.
Collapse
Affiliation(s)
- Li-Li Yin
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Ping-Qian Qi
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yun-Fei Hu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Xiao-Jun Fu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Rui-Shan He
- The Second College of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Meng-Meng Wang
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yan-Juan Deng
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Su-Yi Xiong
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Qi-Wen Yu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Jin-Ping Hu
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Lv Zhou
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Zhi-Bin Zhou
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Ying Xiong
- Department of General Medicine, The Second College of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi Province, China
| | - Huan Deng
- The Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Fourth Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
- Tumor Immunology Institute, Nanchang University, Nanchang 330006, Jiangxi Province, China
- The Ministry of Education Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi Province, China
| |
Collapse
|
|
2
|
Grion BAR, Fonseca PLC, Kato RB, García GJY, Vaz ABM, Jiménez BN, Dambolenea AL, Garcia-Etxebarria K, Brenig B, Azevedo V, Bujanda L, Banales JM, Góes-Neto A. Identification of taxonomic changes in the fecal bacteriome associated with colorectal polyps and cancer: potential biomarkers for early diagnosis. Front Microbiol 2024; 14:1292490. [PMID: 38293554 PMCID: PMC10827328 DOI: 10.3389/fmicb.2023.1292490] [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: 09/11/2023] [Accepted: 12/26/2023] [Indexed: 02/01/2024] Open
Abstract
Colorectal cancer (CRC) commonly arises in individuals with premalignant colon lesions known as polyps, with both conditions being influenced by gut microbiota. Host-related factors and inherent characteristics of polyps and tumors may contribute to microbiome variability, potentially acting as confounding factors in the discovery of taxonomic biomarkers for both conditions. In this study we employed shotgun metagenomics to analyze the taxonomic diversity of bacteria present in fecal samples of 90 clinical subjects (comprising 30 CRC patients, 30 with polyps and 30 controls). Our findings revealed a decrease in taxonomic richness among individuals with polyps and CRC, with significant dissimilarities observed among the study groups. We identified significant alterations in the abundance of specific taxa associated with polyps (Streptococcaceae, Lachnoclostridium, and Ralstonia) and CRC (Lactobacillales, Clostridiaceae, Desulfovibrio, SFB, Ruminococcus, and Faecalibacterium). Clostridiaceae exhibited significantly lower abundance in the early stages of CRC. Additionally, our study revealed a positive co-occurrence among underrepresented genera in CRC, while demonstrating a negative co-occurrence between Faecalibacterium and Desulfovibrio, suggesting potential antagonistic relationships. Moreover, we observed variations in taxonomic richness and/or abundance within the polyp and CRC bacteriome linked to polyp size, tumor stage, dyslipidemia, diabetes with metformin use, sex, age, and family history of CRC. These findings provide potential new biomarkers to enhance early CRC diagnosis while also demonstrating how intrinsic host factors contribute to establishing a heterogeneous microbiome in patients with CRC and polyps.
Collapse
Affiliation(s)
- Beatriz Alessandra Rudi Grion
- Laboratory of Molecular and Computational Biology of Fungi, Institute of Biological Sciences, Department of Microbiology, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Paula Luize Camargos Fonseca
- Integrative Biology Laboratory, Institute of Biological Sciences, Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | | | - Aline Bruna Martins Vaz
- Oswaldo Cruz Foundation (Fiocruz-MG), Minas Gerais, Brazil
- Medical School, Universidade José do Rosário Vellano (UNIFENAS), Belo Horizonte, Brazil
| | - Beatriz Nafría Jiménez
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Ikerbasque, San Sebastian, Spain
| | - Ainhoa Lapitz Dambolenea
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Ikerbasque, San Sebastian, Spain
| | - Koldo Garcia-Etxebarria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Ikerbasque, San Sebastian, Spain
| | - Bertram Brenig
- Institute of Veterinary Medicine, Burckhardtweg, University of Göttingen, Göttingen, Germany
| | - Vasco Azevedo
- Laboratory of Cellular and Molecular Genetics, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Ikerbasque, San Sebastian, Spain
| | - Jesus M. Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute – Donostia University Hospital, Ikerbasque, San Sebastian, Spain
- CIBERehd, Madrid, Spain
- Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain
| | - Aristóteles Góes-Neto
- Laboratory of Molecular and Computational Biology of Fungi, Institute of Biological Sciences, Department of Microbiology, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Graduate Program in Bioinformatics, Federal University of Minas Gerais, Belo Horizonte, Brazil
| |
Collapse
|
|
3
|
Dudun AA, Chesnokova DV, Voinova VV, Bonartsev AP, Bonartseva GA. Changes in the Gut Microbiota Composition during Implantation of Composite Scaffolds Based on Poly(3-hydroxybutyrate) and Alginate on the Large-Intestine Wall. Polymers (Basel) 2023; 15:3649. [PMID: 37688275 PMCID: PMC10489921 DOI: 10.3390/polym15173649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/23/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
The development of biopolymer scaffolds for intestine regeneration is one of the most actively developing areas in tissue engineering. However, intestinal regenerative processes after scaffold implantation depend on the activity of the intestinal microbial community that is in close symbiosis with intestinal epithelial cells. In this work, we study the impact of different scaffolds based on biocompatible poly(3-hydroxybutyrate) (PHB) and alginate (ALG) as well as PHB/ALG scaffolds seeded with probiotic bacteria on the composition of gut microbiota of Wistar rats. Implantation of PHB/ALG scaffolds on the large-intestine wall to close its injury showed that alpha diversity of the gut microbiota was not reduced in rats implanted with different PHB/ALG scaffolds except for the PHB/ALG scaffolds with the inclusion of Lactobacillus spheres (PHB/ALG-L). The composition of the gut microbiota of rats implanted with PHB/ALG scaffolds with probiotic bacteria or in simultaneous use of an antimicrobial agent (PHB/ALG-AB) differed significantly from other experimental groups. All rats with implanted scaffolds demonstrated shifts in the composition of the gut microbiota by individual operational taxonomic units. The PHB/ALG-AB construct led to increased abundance of butyrate-producing bacteria: Ileibacterium sp. dominated in rats with implanted PHB/ALG-L and Lactobacillus sp. and Bifidobacterium sp. dominated in the control group. In addition, the PHB/ALG scaffolds had a favourable effect on the growth of commensal bacteria. Thus, the effect of implantation of the PHB/ALG scaffold compared to other scaffolds on the composition of the gut microbiota was closest to the control variant, which may demonstrate the biocompatibility of this device with the microbiota.
Collapse
Affiliation(s)
- Andrei A. Dudun
- A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, Bld. 2, 119071 Moscow, Russia;
| | - Dariana V. Chesnokova
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234 Moscow, Russia; (D.V.C.); (V.V.V.); (A.P.B.)
| | - Vera V. Voinova
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234 Moscow, Russia; (D.V.C.); (V.V.V.); (A.P.B.)
| | - Anton P. Bonartsev
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1-12, 119234 Moscow, Russia; (D.V.C.); (V.V.V.); (A.P.B.)
| | - Garina A. Bonartseva
- A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, Bld. 2, 119071 Moscow, Russia;
| |
Collapse
|
|
4
|
Alhhazmi AA, Alhamawi RM, Almisned RM, Almutairi HA, Jan AA, Kurdi SM, Almutawif YA, Mohammed-Saeid W. Gut Microbial and Associated Metabolite Markers for Colorectal Cancer Diagnosis. Microorganisms 2023; 11:2037. [PMID: 37630597 PMCID: PMC10457972 DOI: 10.3390/microorganisms11082037] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/29/2023] [Accepted: 07/30/2023] [Indexed: 08/27/2023] Open
Abstract
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the Cochrane Handbook for Systematic Reviews of Interventions. Twenty-four studies were eligible. We identified strong evidence of two microbial markers Fusobacterium and Porphyromonas for ADA vs. CRC, and nine microbial markers Lachnospiraceae-Lachnoclostridium, Ruminococcaceae-Ruminococcus, Parvimonas spp., Parvimonas micra, Enterobacteriaceae, Fusobacterium spp., Bacteroides, Peptostreptococcus-Peptostreptococcus stomatis, Clostridia spp.-Clostridium hylemonae, Clostridium symbiosum, and Porphyromonas-Porphyromonas asaccharolytica for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
Collapse
Affiliation(s)
- Areej A. Alhhazmi
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Renad M. Alhamawi
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Reema M. Almisned
- Seha Polyclinic, P.O. Box 150, Al-Madinah Al-Munawarah 41311, Saudi Arabia;
| | - Hanouf A. Almutairi
- Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), P.O. Box 6900, Thuwal 23955, Saudi Arabia;
| | - Ahdab A. Jan
- Abdulla Fouad Medical Supplies and Services (AFMS), P.O. Box 150, Al-Madinah Al-Munawarah 21414, Saudi Arabia;
| | - Shahad M. Kurdi
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Yahya A. Almutawif
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Waleed Mohammed-Saeid
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia;
| |
Collapse
|
|
5
|
Abstract
The microbiome (bacteria, viruses, and fungi) that exist within a patient's gastrointestinal tract and throughout their body have been increasingly understood to play a critical role in a variety of disease, including a number of cancer histologies. These microbial colonies are reflective of a patient's overall health state, their exposome, and germline genetics. In the case of colorectal adenocarcinoma, significant progress has been made in understanding the mechanism the microbiome plays beyond mere associations in both disease initiation and progression. Importantly, this improved understanding holds the potential to further identify the role these microbes play in colorectal cancer. We hope this improved understanding will be able to be leveraged in the future through either biomarkers or next-generation therapeutics to augment contemporary treatment algorithms through the manipulation of a patient's microbiome-whether through diet, antibiotics, prebiotics, or novel therapeutics. Here we review the role of the microbiome in the setting of patients with stage IV colorectal adenocarcinoma in both the development and progression or disease as well as response to therapeutics.
Collapse
Affiliation(s)
- Samuel Cass
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael G. White
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
6
|
Liu H, Zhang K, Liu P, Xu X, Zhou Y, Gan L, Yao L, Li B, Chen T, Fang N. Improvement Effect of Bifidobacterium animalis subsp. lactis MH-02 in Patients Receiving Resection of Colorectal Polyps: A Randomized, Double-Blind, Placebo-Controlled Trial. Front Immunol 2022; 13:940500. [PMID: 35833120 PMCID: PMC9271559 DOI: 10.3389/fimmu.2022.940500] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/01/2022] [Indexed: 11/24/2022] Open
Abstract
Background Postoperative symptoms, bowel dysfunction and recurrence are common problems after resection of colorectal polyps. We aimed to evaluate the efficacy of Bifidobacterium in the postoperative patients. Methods In this single-center, randomized, double-blind, placebo-controlled trial, adults (≥ 18 years) undergoing endoscopic resection of colorectal polyps were treated with probiotics (Bifidobacterium animalis subsp. lactis MH-02, 2 × 109 colony-forming units per packet) or placebo once daily for 7 days. The primary clinical endpoint was a reduction in the mean total postoperative symptoms score within 7 days postoperatively. Secondary clinical endpoints were the single symptom scores, time to recovery of bowel function, and changes in the intestinal microbiota. This study is registered with the number ChiCTR2100046687. Results A total of 100 individuals were included (48 in probiotic group and 52 in placebo group). No difference was seen in the mean scores between the two groups (0.29 vs. 0.43, P = 0.246). Colorectal polyps size (P = 0.008) and preoperative symptoms (P = 0.032) were influential factors for the primary endpoint. Besides, MH-02 alleviated difficult defecation (P = 0.045), and reduced the time to recovery of bowel function (P = 0.032). High-throughput analysis showed that MH-02 can help restore the diversity of intestinal microbiota, and increased the relative abundance of Bifidobacterium, Roseburia, Gemmiger, Blautia and Ruminococcus, while reduced the relative abundance of Clostridium at genus level (P < 0.05). Conclusion In this prospective trial, MH-02 showed efficacy in patients with resection of colorectal polyps, particularly in the recovery of bowel function, and the changes in the intestinal microbiota may provide evidence for further exploration of the therapeutic mechanisms.
Collapse
Affiliation(s)
- Hui Liu
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Kaige Zhang
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Peng Liu
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Xuan Xu
- Huankui Academy, Nanchang University, Nanchang, China
| | - Yuyang Zhou
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Lihong Gan
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Ling Yao
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Bin Li
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
| | - Tingtao Chen
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China
- *Correspondence: Tingtao Chen, ; Nian Fang,
| | - Nian Fang
- Third Clinical Medical College, Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, China
- *Correspondence: Tingtao Chen, ; Nian Fang,
| |
Collapse
|
|
7
|
Zhou CB, Pan SY, Jin P, Deng JW, Xue JH, Ma XY, Xie YH, Cao H, Liu Q, Xie WF, Zou XP, Sheng JQ, Wang BM, Wang H, Ren JL, Liu SD, Sun YW, Meng XJ, Zhao G, Chen JX, Cui Y, Wang PQ, Guo HM, Yang L, Chen X, Ding J, Yang XN, Wang XK, Qian AH, Hou LD, Wang Z, Chen YX, Fang JY. Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer. Gastroenterology 2022; 162:1933-1947.e18. [PMID: 35167866 DOI: 10.1053/j.gastro.2022.02.015] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 01/25/2022] [Accepted: 02/06/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).
Collapse
Affiliation(s)
- Cheng-Bei Zhou
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Si-Yuan Pan
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Peng Jin
- Department of Gastroenterology, The First Medical Center of Chinese People's Liberation Army General Hospital, The Seventh Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jia-Wen Deng
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jin-Hui Xue
- Department of Clinical Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xin-Yue Ma
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan-Hong Xie
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Cao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qiang Liu
- Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei-Fen Xie
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xiao-Ping Zou
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Jian-Qiu Sheng
- Department of Gastroenterology, The First Medical Center of Chinese People's Liberation Army General Hospital, The Seventh Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Hong Wang
- Department of Gastroenterology, Shanghai Jing'an District Central Hospital, Fudan University, Shanghai, China
| | - Jian-Lin Ren
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Si-De Liu
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yun-Wei Sun
- Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiang-Jun Meng
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gang Zhao
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jin-Xian Chen
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Cui
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Pei-Qin Wang
- Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Hui-Min Guo
- Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Lang Yang
- Department of Gastroenterology, The First Medical Center of Chinese People's Liberation Army General Hospital, The Seventh Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China
| | - Jia Ding
- Department of Gastroenterology, Shanghai Jing'an District Central Hospital, Fudan University, Shanghai, China
| | - Xiao-Ning Yang
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Xin-Ke Wang
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ai-Hua Qian
- Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li-Dan Hou
- Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zheng Wang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology; Shanghai Institute of Digestive Disease; NHC Key Laboratory of Digestive Diseases; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| |
Collapse
|
|
8
|
Yu L, Zhao G, Wang L, Zhou X, Sun J, Li X, Zhu Y, He Y, Kofonikolas K, Bogaert D, Dunlop M, Zhu Y, Theodoratou E, Li X. A systematic review of microbial markers for risk prediction of colorectal neoplasia. Br J Cancer 2022; 126:1318-1328. [PMID: 35292756 PMCID: PMC9042911 DOI: 10.1038/s41416-022-01740-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 12/23/2021] [Accepted: 02/03/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Substantial evidence indicates that dysbiosis of the gut microbial community is associated with colorectal neoplasia. This review aims to systematically summarise the microbial markers associated with colorectal neoplasia and to assess their predictive performance. METHODS A comprehensive literature search of MEDLINE and EMBASE databases was performed to identify eligible studies. Observational studies exploring the associations between microbial biomarkers and colorectal neoplasia were included. We also included prediction studies that constructed models using microbial markers to predict CRC and adenomas. Risk of bias for included observational and prediction studies was assessed. RESULTS Forty-five studies were included to assess the associations between microbial markers and colorectal neoplasia. Nine faecal microbiotas (i.e., Fusobacterium, Enterococcus, Porphyromonas, Salmonella, Pseudomonas, Peptostreptococcus, Actinomyces, Bifidobacterium and Roseburia), two oral pathogens (i.e., Treponema denticola and Prevotella intermedia) and serum antibody levels response to Streptococcus gallolyticus subspecies gallolyticus were found to be consistently associated with colorectal neoplasia. Thirty studies reported prediction models using microbial markers, and 83.3% of these models had acceptable-to-good discrimination (AUROC > 0.75). The results of predictive performance were promising, but most of the studies were limited to small number of cases (range: 9-485 cases) and lack of independent external validation (76.7%). CONCLUSIONS This review provides insight into the evidence supporting the association between different types of microbial species and their predictive value for colorectal neoplasia. Prediction models developed from case-control studies require further external validation in high-quality prospective studies. Further studies should assess the feasibility and impact of incorporating microbial biomarkers in CRC screening programme.
Collapse
Affiliation(s)
- Lili Yu
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Gang Zhao
- Center for Disease Control and Prevention of Hangzhou, Hangzhou, China
| | - Lijuan Wang
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Zhou
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Sun
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinxuan Li
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yingshuang Zhu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Yazhou He
- Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, China
| | | | - Debby Bogaert
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Malcolm Dunlop
- Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Yimin Zhu
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK
- Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Xue Li
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
Xue JH, Xie YH, Zou TH, Qian Y, Kang ZR, Zhou CB, Pan SY, Xia TX, Chen YX, Fang JY. Fecal Fusobacterium nucleatum as a predictor for metachronous colorectal adenoma after endoscopic polypectomy. J Gastroenterol Hepatol 2021; 36:2841-2849. [PMID: 34121231 DOI: 10.1111/jgh.15559] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 04/02/2021] [Accepted: 05/19/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Fusobacterium nucleatum is increasingly being recognized as an important risk factor in colorectal cancer and colorectal adenoma. Endoscopic polypectomy is associated with a decreased incidence of colorectal cancer; however, patients still suffer from a risk of metachronous adenoma. Currently, there are few effective non-invasive factors that may predict metachronous colorectal adenoma. Here, we evaluated the performance of F. nucleatum in predicting metachronous adenoma. METHODS Fecal samples and clinical information of patients before endoscopic polypectomy were collected from 367 patients in a retrospective cohort, and 238 patients in a prospective cohort. The abundance of fecal F. nucleatum was measured via quantitative polymerase chain reaction. Surveillance colonoscopies were conducted between 1 and 3 years after polypectomy (average follow-up 27.07 months for the retrospective cohort & 22.57 months for the prospective cohort) to identify metachronous adenoma. Candidate predictive factors and cut-off value of F. nucleatum abundance were identified from the retrospective cohort and then validated in the prospective cohort. RESULTS A high abundance of fecal F. nucleatum was found to be an independent risk factor for metachronous adenomas (odds ratio, 6.38; P < 0.001) in the retrospective cohort and was validated in the prospective cohort with a specificity of 65.00%, and a sensitivity of 73.04%, and an overall performance with the area under the curve of 0.73. CONCLUSION Fecal abundance of F. nucleatum may be a reliable predictor for metachronous adenoma after endoscopic polypectomy.
Collapse
Affiliation(s)
- Jin-Hui Xue
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan-Hong Xie
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian-Hui Zou
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Qian
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zi-Ran Kang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Cheng-Bei Zhou
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Si-Yuan Pan
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian-Xue Xia
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease; State Key Laboratory for Oncogenes and Related Genes; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
|
11
|
Koulouris A, Tsagkaris C, Messaritakis I, Gouvas N, Sfakianaki M, Trypaki M, Spyrou V, Christodoulakis M, Athanasakis E, Xynos E, Tzardi M, Mavroudis D, Souglakos J. Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies. Cancers (Basel) 2021; 13:3522. [PMID: 34298740 PMCID: PMC8304269 DOI: 10.3390/cancers13143522] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/09/2021] [Accepted: 07/12/2021] [Indexed: 12/12/2022] Open
Abstract
Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients' quality of life, as well.
Collapse
Affiliation(s)
- Andreas Koulouris
- Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece; (A.K.); (M.S.); (M.T.); (D.M.); (J.S.)
- Department of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Greece
| | | | - Ippokratis Messaritakis
- Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece; (A.K.); (M.S.); (M.T.); (D.M.); (J.S.)
| | - Nikolaos Gouvas
- Medical School, University of Cyprus, Nicosia 20537, Cyprus;
| | - Maria Sfakianaki
- Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece; (A.K.); (M.S.); (M.T.); (D.M.); (J.S.)
| | - Maria Trypaki
- Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece; (A.K.); (M.S.); (M.T.); (D.M.); (J.S.)
| | - Vasiliki Spyrou
- Department of Radiation Oncology, Hygeia Hospital, 15123 Athens, Greece;
| | - Manousos Christodoulakis
- Department of General Surgery, Venizeleio General Hospital, Leoforos Knossou 44, 71409 Heraklion, Greece;
| | - Elias Athanasakis
- Department of Surgery, University General Hospital of Heraklion, 71110 Heraklion, Greece;
| | - Evangelos Xynos
- Department of Surgery, Creta Interclinic Hospital of Heraklion, 71305 Heraklion, Greece;
| | - Maria Tzardi
- Laboratory of Pathology, University General Hospital of Heraklion, 70013 Heraklion, Greece;
| | - Dimitrios Mavroudis
- Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece; (A.K.); (M.S.); (M.T.); (D.M.); (J.S.)
- Department of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Greece
| | - John Souglakos
- Laboratory of Translational Oncology, Medical School, University of Crete, 70013 Heraklion, Greece; (A.K.); (M.S.); (M.T.); (D.M.); (J.S.)
- Department of Medical Oncology, University Hospital of Heraklion, 71110 Heraklion, Greece
| |
Collapse
|
|
12
|
Aprile F, Bruno G, Palma R, Mascellino MT, Panetta C, Scalese G, Oliva A, Severi C, Pontone S. Microbiota Alterations in Precancerous Colon Lesions: A Systematic Review. Cancers (Basel) 2021; 13:cancers13123061. [PMID: 34205378 PMCID: PMC8234190 DOI: 10.3390/cancers13123061] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/09/2021] [Accepted: 06/14/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Even with recent advances, gut microbiota is still one of the most demanding challenges that research needs to handle. In particular, given its deep impact on gastrointestinal health, microbiota could explain the development and progression of certain diseases. Moreover, it could be used as a potential predictive biomarker. Given this, the relationship between intestinal microbiota and colorectal adenoma, considered a premalignant lesion leading to carcinoma, has been deeply evaluated. This review highlights the historical and novel data on microbiota characteristics in adenoma patients to provide an updated summary of current knowledge and its limits. Abstract Gut microbiota plays an important role in human health. It may promote carcinogenesis and is related to several diseases of the gastrointestinal tract. This study of microbial dysbiosis in the etiology of colorectal adenoma aimed to investigate the possible causative role of microbiota in the adenoma–carcinoma sequence and its possible preventive role. A systematic, PRISMA-guided review was performed. The PubMed database was searched using “adenoma microbiota” and selecting original articles between January 2010 and May 2020 independently screened. A higher prevalence of Proteobacteria, Fusobacteria, and Bacteroidetes phyla was observed in the fecal luminal and mucosa-associated microbiota of patients with adenoma. However, other studies provided evidence of depletion of Clostridium, Faecalibacterium, Bacteroides and Romboutsia. Results on the relationship between adenoma endoscopic resection and microbiota were inconsistent. In conclusion, none of the analyzed studies developed a predictive model that could differentiate adenoma from non-adenoma patients, and therefore, to prevent cancer progression. The impact of adenoma’s endoscopic resection on microbiota was investigated, but the results were inconclusive. Further research in the field is required.
Collapse
Affiliation(s)
- Francesca Aprile
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Giovanni Bruno
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Rossella Palma
- Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.P.); (C.P.)
| | - Maria Teresa Mascellino
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy; (M.T.M.); (A.O.)
| | - Cristina Panetta
- Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.P.); (C.P.)
| | - Giulia Scalese
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy; (M.T.M.); (A.O.)
| | - Carola Severi
- Department of Translational and Precision Medicine, Gastroenterology Unit, Sapienza University of Rome, 00161 Rome, Italy; (F.A.); (G.B.); (G.S.); (C.S.)
| | - Stefano Pontone
- Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; (R.P.); (C.P.)
- Correspondence: ; Tel.: +39-06-49975568
| |
Collapse
|
|
13
|
Huang QY, Yao F, Zhou CR, Huang XY, Wang Q, Long H, Wu QM. Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes. World J Clin Cases 2020; 8:6213-6228. [PMID: 33392303 PMCID: PMC7760447 DOI: 10.12998/wjcc.v8.i24.6213] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 10/13/2020] [Accepted: 11/02/2020] [Indexed: 02/05/2023] Open
Abstract
The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars’ attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota–CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.
Collapse
Affiliation(s)
- Qi-You Huang
- Institute of Infection, Immunology and Tumor Microenvironment, Medical College, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China
| | - Fei Yao
- Institute of Infection, Immunology and Tumor Microenvironment, Medical College, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China
| | - Chuan-Ren Zhou
- Institute of Infection, Immunology and Tumor Microenvironment, Medical College, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China
| | - Xiao-Ying Huang
- Institute of Infection, Immunology and Tumor Microenvironment, Medical College, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China
| | - Qiang Wang
- Institute of Infection, Immunology and Tumor Microenvironment, Medical College, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China
| | - Hui Long
- Department of Gastroenterology, Tianyou Affiliated Hospital, Wuhan University of Science and Technology, Wuhan 430064, Hubei Province, China
| | - Qing-Ming Wu
- Institute of Infection, Immunology and Tumor Microenvironment, Medical College, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China
| |
Collapse
|
|
14
|
Zheng Y, Yu J, Liang C, Li S, Wen X, Li Y. Characterization on gut microbiome of PCOS rats and its further design by shifts in high-fat diet and dihydrotestosterone induction in PCOS rats. Bioprocess Biosyst Eng 2020; 44:953-964. [PMID: 32157446 DOI: 10.1007/s00449-020-02320-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 02/26/2020] [Indexed: 12/11/2022]
Abstract
Polycystic ovary syndrome (PCOS) is associated with gut microbiota disturbance. Emerging evidence has shown that gut microbiota plays a major role in the development of PCOS. To better understand how the gut microbiota contributes to the development of PCOS, we investigated the influences of high-fat diet and hyperandrogenism, independently or synergistically, have on the gut microbiota in rats. Furthermore, we explored the associations between gut microbiota and hyperandrogenism or other hallmarks of PCOS. Twenty female SD rats were randomized at aged 3 weeks into 4 groups (n = 5, each); HA: PCOS rats fed with ordinary diet; HF: rats with high-fat diet (HFD); HA-HF: PCOS rats fed with HFD; and C: control rats with ordinary diet. PCOS rat model was induced by 5α-dihydrotestosterone (DHT) injection for 6 weeks. The fasting blood glucose (FBG), plasma insulin, testosterone, free testosterone, TNF-α, MDA, SOD, LPS, TLR4, TG, TC, HDL-C, and LDL-C levels were measured. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing. The results showed that rats in the HA and HA-HF group displayed abnormal estrous cycles with increasing androgen level and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Compare with the C group, relative abundance of the Bacteroidetes phylum decreased significantly in the other groups (P < 0.05). The Chao1 was the highest in the group C and significantly higher than the HA-HF group (P < 0.05). T, FT, insulin, MDA, LPS, and TNF-α levels had the negative correlation with the richness of community (Chao1 index) in the gut. The rats in the HF and HA-HF groups tended to have lower Shannon and Simpson indices than the C group (P < 0.01, respectively). However, there were no significant differences between C group and the HA group in the Shannon and Simpson values. Beta diversity analysis was then performed based on a weighted UniFrac analysis. The PCoA plots showed a clear separation of the C group from the other groups. ANOSIM analysis of variance confirmed that there were statistically significant separations between the C group and the HA, HA-HF, and HF groups (P < 0.01, respectively). These results showed that DHT with HFD could lower diversity of the gut microbial community. Both HFD and DHT could shift the overall gut microbial composition and change the composition of the microbial community in gut. Furthermore, our analyses demonstrated that the levels of TG, MDA, TNF-α, LPS, TLR4, T, FT, FINS, and HDL-C were correlated with the changes of in the gut microbiome. HFD and DHT were associated with the development and pathology of PCOS by shaping gut microbial communities.
Collapse
Affiliation(s)
- Yanhua Zheng
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jingwei Yu
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Chengjie Liang
- Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Shuna Li
- The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiaohui Wen
- The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yanmei Li
- School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
| |
Collapse
|
|
15
|
Wu CY. Microbiota alterations after colon adenoma resection. J Gastroenterol Hepatol 2019; 34:1669-1670. [PMID: 31726487 DOI: 10.1111/jgh.14893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Chun-Ying Wu
- Division of Translational Research and Center of Excellence for Cancer Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Biomedical Informatics, Institute of Clinical Medicine, and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.,Department of Public Health, China Medical University, Taichung, Taiwan.,National Health Research Institutes, National Institute of Cancer Research, Miaoli, Taiwan.,Taiwan Microbiota Consortium, Taipei, Taiwan
| |
Collapse
|