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Cai Z, Zhang M, Zhou L, Xiong Y, Wang H, Chen Y, Yuan J. Kai-Xin-San polysaccharides exert therapeutic effects on D-gal and Aβ 25-35-induced AD rats by regulating gut microbiota and metabolic profile. Int J Biol Macromol 2025; 306:141850. [PMID: 40058438 DOI: 10.1016/j.ijbiomac.2025.141850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 02/24/2025] [Accepted: 03/06/2025] [Indexed: 05/11/2025]
Abstract
Metabolic abnormalities and gut microbiota imbalance are intricately linked to the onset and progression of Alzheimer's disease (AD). Kai-Xin-San (KXS) is a traditional herbal formula known for its therapeutic effects on AD. Our previous research indicated that Kai-Xin-San polysaccharide (KXS-P) exhibits a significant therapeutic impact on AD, but the precise mechanisms remain incompletely understood. In this study, untargeted fecal metabolomics and 16S rRNA gene sequencing were used to investigate the potential mechanisms by which KXS-P acts against AD. Key metabolites and gut microbial species were identified using multivariate analysis and a comprehensive examination of intestinal microecology. Our findings revealed that KXS-P improves lipid metabolism in AD rats by modulating a series of lipid molecules and bile acid levels. Additionally, KXS-P regulated gut microbiota composition and restored the symbiotic relationships within the gut microbiome. Notably, the anti-inflammatory effect of KXS-P may be related to its regulation of specific lipotypes levels and the abundance of Romboutsia, Bifidobacterium and Alloprevotella. KXS-P demonstrates the ability to alleviate symptoms of AD rats through multiple mechanisms: ① Improving lipid metabolism and maintaining lipid homeostasis; ② Reducing neuronal and inflammatory damage; ③ Regulating the composition and symbiotic relationships of gut microbiota to preserve intestinal microecological balance.
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Affiliation(s)
- Zhinan Cai
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Min Zhang
- Nanchang Key Laboratory of Detection and Control of Food Safety, Nanchang Inspection and Testing Center, Nanchang 330012, China
| | - Lifen Zhou
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Yongchang Xiong
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Huijuan Wang
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Ying Chen
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Jinbin Yuan
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
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Ma Y, Zhou Y, Xie G, Chen H, Huangfu Y, Shen L, Liu Y, Wang P. HEX-1 reduces colitis-driven colorectal cancer via inactivating the prolyl isomerase PIN1 sensitization and remodeling the gut microbiota. Discov Oncol 2025; 16:565. [PMID: 40251462 PMCID: PMC12008109 DOI: 10.1007/s12672-025-02338-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 04/08/2025] [Indexed: 04/20/2025] Open
Abstract
Metabolic reprogramming, a pivotal hallmark of cancer, plays a crucial role in both the initiation and progression of colorectal cancer (CRC). Despite the vast unknowns surrounding the identity and biological activities of most natural metabolites in diseases, our study, utilizing native metabolomics results through GC-MS/MS, identified a small molecule, 4,4-Dimethyl-2-cyclohexen-1-one, named HEX-1 in the serum of CRC patients. We have further explored and assessed its biological activities. HEX-1 suppressed the proliferation of cancer cells and tumorigenesis via the inactivation and sensitization of PIN1. Notably, HEX-1 exhibits similar functional effects as all-trans retinoic acid (atRA) but stands out by not inducing the degradation of PIN1 mRNA or protein expression, unlike biological compounds associated with atRA. HEX-1 demonstrated the ability to induce G1/S arrest in vitro and ameliorate the progression of inflammatory CRC in mice by remodeling the gut microbiota. As volatile organic compounds (VOCs), HEX-1 could be detected feasibly. Its unique ability to penetrate whole cell populations positions it as a promising approach for cancer therapy and as an enhancer for chemotherapy and immunotherapy. The findings suggest that HEX-1 holds the potential as a valuable addition to the armamentarium against CRC.
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Affiliation(s)
- Yanhui Ma
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yunlan Zhou
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Guohua Xie
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Hui Chen
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yuchan Huangfu
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Lisong Shen
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- Institute of Artificial Intelligence Medicine, Shanghai Academy of Experimental Medicine, Shanghai, 200092, China
| | - Yi Liu
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
- Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
- Institute of Artificial Intelligence Medicine, Shanghai Academy of Experimental Medicine, Shanghai, 200092, China.
| | - Ping Wang
- Department of Laboratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
- Institute of Artificial Intelligence Medicine, Shanghai Academy of Experimental Medicine, Shanghai, 200092, China.
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Zhang H, Zhou Y, Jiang YH, Hu WP, Huang LL, Lin HX, Zuo ZG, Du JM, Lou YL. Altered microbiota of rectal mucosa in rectal cancer patients. World J Gastroenterol 2025; 31:105248. [PMID: 40248061 PMCID: PMC12001164 DOI: 10.3748/wjg.v31.i13.105248] [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: 01/16/2025] [Revised: 02/27/2025] [Accepted: 03/21/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND With advances in sequencing techniques, microbiota dysbiosis and pathogenic microbes that accelerate colorectal cancer progression have been identified and widely reported. However, few studies have focused on the microbiota taxa of rectal mucus in rectal cancer (RC) patients. Here, we analyzed the composition and characteristics of the rectal mucosa microbiota of RC patients from Wenzhou city, China, and compared the results with those of healthy controls. AIM To explore the changes in the characteristics of the rectal mucosal flora associated with RC, and identify biomarkers of microbe taxa for RC. METHODS Rectal mucosa samples from a Chinese cohort of 72 recently diagnosed RC patients and 71 healthy controls were obtained. A validation cohort, which included 22 RC patients and 60 healthy controls, was also established. Changes in the rectal mucosal flora were observed by cultivation, 16S ribosomal DNA gene sequencing analysis and quantitative polymerase chain reaction analysis. RESULTS The 16S ribosomal DNA results demonstrated that RC patients presented increased bacterial community richness and alpha diversity as well as an altered rectal mucosal microbiota, with depletion of Proteobacteria and Thermi and enrichment of Bacteroidetes and Fusobacteria in cancerous mucosal tissues (CM) and enrichment of Firmicutes and Cyanobacteria in adjacent noncancerous mucosal tissues (AM). The culture results showed that the mean loads of Escherichia coli, Bifidobacterium, Enterococcus, and Lactobacillus were significantly reduced in RC patients. The ratios of Prevotella to Ruminococcus [areas under the receiver operating curve: 0.795 in AM vs normal control mucosa (NM), 0.77 in CM vs NM] and of Prevotella stercorea to Propionibacterium acnes (areas under the receiver operating curve: 0.808 in AM vs NM, 0.843 in CM vs NM) exhibited excellent abilities to differentiate between healthy controls and RC patients. CONCLUSION RC patients have an altered rectal mucosal microbiota, and the ratio of Prevotella to Ruminococcus or the ratio of Prevotella stercorea to Propionibacterium acnes may serve as a marker for RC diagnosis.
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Affiliation(s)
- Hao Zhang
- Department of Laboratory Medicine, Hangzhou Geriatric Hospital, Hangzhou 310022, Zhejiang Province, China
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Yan Zhou
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - You-Heng Jiang
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China
| | - Wan-Ping Hu
- Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Lu-Lu Huang
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Hai-Xia Lin
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Zhi-Gui Zuo
- Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Ji-Mei Du
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Yong-Liang Lou
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
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Bakir-Gungor B, Temiz M, Canakcimaksutoglu B, Yousef M. Prediction of colorectal cancer based on taxonomic levels of microorganisms and discovery of taxonomic biomarkers using the Grouping-Scoring-Modeling (G-S-M) approach. Comput Biol Med 2025; 187:109813. [PMID: 39929003 DOI: 10.1016/j.compbiomed.2025.109813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 01/09/2025] [Accepted: 02/05/2025] [Indexed: 02/12/2025]
Abstract
Colorectal cancer (CRC) is one of the most prevalent forms of cancer globally. The human gut microbiome plays an important role in the development of CRC and serves as a biomarker for early detection and treatment. This research effort focuses on the identification of potential taxonomic biomarkers of CRC using a grouping-based feature selection method. Additionally, this study investigates the effect of incorporating biological domain knowledge into the feature selection process while identifying CRC-associated microorganisms. Conventional feature selection techniques often fail to leverage existing biological knowledge during metagenomic data analysis. To address this gap, we propose taxonomy-based Grouping Scoring Modeling (G-S-M) method that integrates biological domain knowledge into feature grouping and selection. In this study, using metagenomic data related to CRC, classification is performed at three taxonomic levels (genus, family and order). The MetaPhlAn tool is employed to determine the relative abundance values of species in each sample. Comparative performance analyses involve six feature selection methods and four classification algorithms. When experimented on two CRC associated metagenomics datasets, the highest performance metric, yielding an AUC of 0.90, is observed at the genus taxonomic level. At this level, 7 out of top 10 groups (Parvimonas, Peptostreptococcus, Fusobacterium, Gemella, Streptococcus, Porphyromonas and Solobacterium) were commonly identified for both datasets. Moreover, the identified microorganisms at genus, family, and order levels are thoroughly discussed via refering to CRC-related metagenomic literature. This study not only contributes to our understanding of CRC development, but also highlights the applicability of taxonomy-based G-S-M method in tackling various diseases.
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Affiliation(s)
- Burcu Bakir-Gungor
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gul University, Kayseri, 38080, Turkey
| | - Mustafa Temiz
- Department of Electrical and Computer Engineering, Faculty of Engineering, Abdullah Gul University, Kayseri, 38080, Turkey.
| | - Beyza Canakcimaksutoglu
- Department of Bioengineering, Faculty of Life and Natural Science, Abdullah Gul University, Kayseri, 38080, Turkey
| | - Malik Yousef
- Department of Information Systems, Zefat Academic College, Zefat, 13206, Israel; Galilee Digital Health Research Center (GDH), Zefat Academic College, Israel
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5
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Giordano G, Mastrantoni L, Terranova R, Colloca GF, Zuccalà G, Landi F. The role of Mediterranean diet in cancer incidence and mortality in the older adults. NPJ AGING 2024; 10:61. [PMID: 39639020 PMCID: PMC11621705 DOI: 10.1038/s41514-024-00186-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 11/18/2024] [Indexed: 12/07/2024]
Abstract
The magnitude of benefit of Mediterranean diet in cancer prevention and mortality in older adults is still unclear, therefore we conducted a systematic review and meta-analysis. Outcomes considered were cancer incidence and cancer mortality. In studies evaluating cancer incidence as a time-to-event endpoint and adherence as quantiles, HR was 0.885 (95% CI 0.773-1.013, I2 = 44%). Including ORs, exploratory pooled effect size was 0.876 (0.794-0.966, I2 = 34%), consistently with results of studies evaluating ORs for adherence as one-point increase (OR 0.744, 0.570-0.972, I2 = 90%). No clear benefit was observed on cancer mortality, with pooled HR of 0.935 (0.800-1.093, I2 = 0%). Significant differences were observed for ORs according to cancer type but not between medium and high adherence for both outcomes. Certainty of evidence was low. Our findings suggest that MD could play a protective role in cancer incidence in advanced age, but no clear effect on cancer mortality was observed.
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Affiliation(s)
- Giulia Giordano
- Department of Geriatrics, Orthopaedics and Rheumathological Sciences, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy.
| | - Luca Mastrantoni
- Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
| | - Roberta Terranova
- Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy
- Geriatrics, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giuseppe Ferdinando Colloca
- Department of Imaging Diagnostic, Oncologic radiotherapy and Haematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giuseppe Zuccalà
- Department of Geriatrics, Orthopaedics and Rheumathological Sciences, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy
| | - Francesco Landi
- Department of Geriatrics, Orthopaedics and Rheumathological Sciences, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy
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Bakir-Gungor B, Temiz M, Inal Y, Cicekyurt E, Yousef M. CCPred: Global and population-specific colorectal cancer prediction and metagenomic biomarker identification at different molecular levels using machine learning techniques. Comput Biol Med 2024; 182:109098. [PMID: 39293338 DOI: 10.1016/j.compbiomed.2024.109098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 08/29/2024] [Accepted: 08/31/2024] [Indexed: 09/20/2024]
Abstract
Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related deaths. Recent research highlights the pivotal role of the gut microbiota in CRC development and progression. Understanding the complex interplay between disease development and metagenomic data is essential for CRC diagnosis and treatment. Current computational models employ machine learning to identify metagenomic biomarkers associated with CRC, yet there is a need to improve their accuracy through a holistic biological knowledge perspective. This study aims to evaluate CRC-associated metagenomic data at species, enzymes, and pathway levels via conducting global and population-specific analyses. These analyses utilize relative abundance values from human gut microbiome sequencing data and robust classification models are built for disease prediction and biomarker identification. For global CRC prediction and biomarker identification, the features that are identified by SelectKBest (SKB), Information Gain (IG), and Extreme Gradient Boosting (XGBoost) methods are combined. Population-based analysis includes within-population, leave-one-dataset-out (LODO) and cross-population approaches. Four classification algorithms are employed for CRC classification. Random Forest achieved an AUC of 0.83 for species data, 0.78 for enzyme data and 0.76 for pathway data globally. On the global scale, potential taxonomic biomarkers include ruthenibacterium lactatiformanas; enzyme biomarkers include RNA 2' 3' cyclic 3' phosphodiesterase; and pathway biomarkers include pyruvate fermentation to acetone pathway. This study underscores the potential of machine learning models trained on metagenomic data for improved disease prediction and biomarker discovery. The proposed model and associated files are available at https://github.com/TemizMus/CCPRED.
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Affiliation(s)
- Burcu Bakir-Gungor
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gul University, Kayseri, 38080, Turkey
| | - Mustafa Temiz
- Department of Electrical and Computer Engineering, Faculty of Engineering, Abdullah Gul University, Kayseri, 38080, Turkey.
| | - Yasin Inal
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gul University, Kayseri, 38080, Turkey
| | - Emre Cicekyurt
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gul University, Kayseri, 38080, Turkey
| | - Malik Yousef
- Department of Information Systems, Zefat Academic College, Zefat, 13206, Israel; Galilee Digital Health Research Center (GDH), Zefat Academic College, Israel
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Wang S, Jiang Y, Che L, Wang RH, Li SC. Enhancing insights into diseases through horizontal gene transfer event detection from gut microbiome. Nucleic Acids Res 2024; 52:e61. [PMID: 38884260 DOI: 10.1093/nar/gkae515] [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: 09/28/2023] [Revised: 04/23/2024] [Accepted: 06/04/2024] [Indexed: 06/18/2024] Open
Abstract
Horizontal gene transfer (HGT) phenomena pervade the gut microbiome and significantly impact human health. Yet, no current method can accurately identify complete HGT events, including the transferred sequence and the associated deletion and insertion breakpoints from shotgun metagenomic data. Here, we develop LocalHGT, which facilitates the reliable and swift detection of complete HGT events from shotgun metagenomic data, delivering an accuracy of 99.4%-verified by Nanopore data-across 200 gut microbiome samples, and achieving an average F1 score of 0.99 on 100 simulated data. LocalHGT enables a systematic characterization of HGT events within the human gut microbiome across 2098 samples, revealing that multiple recipient genome sites can become targets of a transferred sequence, microhomology is enriched in HGT breakpoint junctions (P-value = 3.3e-58), and HGTs can function as host-specific fingerprints indicated by the significantly higher HGT similarity of intra-personal temporal samples than inter-personal samples (P-value = 4.3e-303). Crucially, HGTs showed potential contributions to colorectal cancer (CRC) and acute diarrhoea, as evidenced by the enrichment of the butyrate metabolism pathway (P-value = 3.8e-17) and the shigellosis pathway (P-value = 5.9e-13) in the respective associated HGTs. Furthermore, differential HGTs demonstrated promise as biomarkers for predicting various diseases. Integrating HGTs into a CRC prediction model achieved an AUC of 0.87.
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Affiliation(s)
- Shuai Wang
- City University of Hong Kong Shenzhen Research Institute, Shenzhen, China
- Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
| | - Yiqi Jiang
- City University of Hong Kong Shenzhen Research Institute, Shenzhen, China
- Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
| | - Lijia Che
- City University of Hong Kong Shenzhen Research Institute, Shenzhen, China
- Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
| | - Ruo Han Wang
- City University of Hong Kong Shenzhen Research Institute, Shenzhen, China
- Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
| | - Shuai Cheng Li
- City University of Hong Kong Shenzhen Research Institute, Shenzhen, China
- Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong
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Tian R, Guan M, Chen L, Wan Y, He L, Zhao Z, Gao T, Zong L, Chang J, Zhang J. Mechanism insights into the histopathological changes of polypropylene microplastics induced gut and liver in zebrafish. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 280:116537. [PMID: 38852469 DOI: 10.1016/j.ecoenv.2024.116537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/20/2024] [Accepted: 05/30/2024] [Indexed: 06/11/2024]
Abstract
Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 μm across varying concentrations (300 mg/L and 600 mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.
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Affiliation(s)
- Ran Tian
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Miao Guan
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Lei Chen
- Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
| | - Yaming Wan
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Le He
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Ziwen Zhao
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Ting Gao
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Linhao Zong
- Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China
| | - Jiang Chang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.
| | - Junfeng Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, China.
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Pandit P, Shirke C, Bhatia N, Godad A, Belemkar S, Patel J, Zine S. An Overview of Recent Findings that Shed Light on the Connection between Fat and Cancer. Endocr Metab Immune Disord Drug Targets 2024; 24:178-193. [PMID: 37489790 DOI: 10.2174/1871530323666230724141942] [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: 12/02/2022] [Revised: 05/27/2023] [Accepted: 06/08/2023] [Indexed: 07/26/2023]
Abstract
Obesity and cancer have been found to have a direct link in epidemiological studies. Obesity raises the risk of cancer and associated chronic disorders. Furthermore, an imbalance of adipokines, like leptins, plays a crucial role in neoplasm pathogenesis, cell migration, and thereby, cancer metastasis. Also, leptin increases human epidermal growth factor receptor 2 (HER2) protein levels through the STAT3-mediated (signal transducer and activator of transcription) upregulation of heat shock protein (Hsp90) in breast cancer cells. It has been noticed that insulin and insulin-like growth factors (IGFs) act as mitosis activators in the host and cancerous breast epithelial cells. The condition of hyperinsulinemia explains the positive association between colorectal cancer and obesity. Furthermore, in prostate cancer, an alteration in sex hormone levels, testosterone and dihydrotestosterone, has been reported to occur, along with increased oxidative stress, which is the actual cause of the tumors. Whereas, there have been two interconnected factors that play a crucial role in the psychological cycle concerned with lung cancer. The review article focuses on all the prospects of etiological mechanisms that have found linkage with obesity and breast, colon, lung, and prostate cancers. Furthermore, the article has also highlighted how these new insights into the processes occur and, due to which reasons, obesity contributes to tumorigenesis. This review provides a detailed discussion on the progression, which can assist in the development of new and innovative techniques to interfere in this process, and it has been supported with insights based on evidence literature on approved clinical treatments for obesity and cancer.
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Affiliation(s)
- Parth Pandit
- Department of Pharmacology, University of Strathclyde, Glasgow, UK
| | - Chaitanya Shirke
- Department of Pharmaceutics, NMIMS Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management - (SPPSPTM), Mumbai, India
| | - Nirav Bhatia
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
| | - Angel Godad
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, India
| | - Sateesh Belemkar
- Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V. M. Road, Vile Parle (W), Mumbai, India
| | - Jayshree Patel
- Department of Quality Assurance, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
| | - Sandip Zine
- Department of Pharmaceutical Chemistry, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V. M. Road, Vile Parle (W), Mumbai, India
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10
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Widjaja F, Rietjens IMCM. From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes. Biomedicines 2023; 11:2658. [PMID: 37893032 PMCID: PMC10603957 DOI: 10.3390/biomedicines11102658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/22/2023] [Accepted: 09/24/2023] [Indexed: 10/29/2023] Open
Abstract
The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine-feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either -20 °C for up to a few months or -80 °C for a longer period-up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.
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Affiliation(s)
- Frances Widjaja
- Division of Toxicology, Wageningen University & Research, 6708 WE Wageningen, The Netherlands;
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11
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Yu S, Ding Y, Wang X, Kin Ng S, Cao S, Liu W, Guo Z, Xie Y, Hong S, Xu L, Li X, Li J, Lv W, Peng S, Li Y, Sung JJ, Yu J, Xiao H. Intratumoral Bacteria Dysbiosis Is Associated with Human Papillary Thyroid Cancer and Correlated with Oncogenic Signaling Pathways. ENGINEERING 2023; 28:179-192. [DOI: 10.1016/j.eng.2023.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Bagyánszki M, Bódi N. Key elements determining the intestinal region-specific environment of enteric neurons in type 1 diabetes. World J Gastroenterol 2023; 29:2704-2716. [PMID: 37274063 PMCID: PMC10237112 DOI: 10.3748/wjg.v29.i18.2704] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 03/28/2023] [Accepted: 04/17/2023] [Indexed: 05/11/2023] Open
Abstract
Diabetes, as a metabolic disorder, is accompanied with several gastrointestinal (GI) symptoms, like abdominal pain, gastroparesis, diarrhoea or constipation. Serious and complex enteric nervous system damage is confirmed in the background of these diabetic motility complaints. The anatomical length of the GI tract, as well as genetic, developmental, structural and functional differences between its segments contribute to the distinct, intestinal region-specific effects of hyperglycemia. These observations support and highlight the importance of a regional approach in diabetes-related enteric neuropathy. Intestinal large and microvessels are essential for the blood supply of enteric ganglia. Bidirectional morpho-functional linkage exists between enteric neurons and enteroglia, however, there is also a reciprocal communication between enteric neurons and immune cells on which intestinal microbial composition has crucial influence. From this point of view, it is more appropriate to say that enteric neurons partake in multidirectional communication and interact with these key players of the intestinal wall. These interplays may differ from segment to segment, thus, the microenvironment of enteric neurons could be considered strictly regional. The goal of this review is to summarize the main tissue components and molecular factors, such as enteric glia cells, interstitial cells of Cajal, gut vasculature, intestinal epithelium, gut microbiota, immune cells, enteroendocrine cells, pro-oxidants, antioxidant molecules and extracellular matrix, which create and determine a gut region-dependent neuronal environment in diabetes.
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Affiliation(s)
- Mária Bagyánszki
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged H-6726, Hungary
| | - Nikolett Bódi
- Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged H-6726, Hungary
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13
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He L, Yang BZ, Ma YJ, Wen L, Liu F, Zhang XJ, Liu TQ. Differences in clinical features and gut microbiota between individuals with methamphetamine casual use and methamphetamine use disorder. Front Cell Infect Microbiol 2023; 13:1103919. [PMID: 36909722 PMCID: PMC9996337 DOI: 10.3389/fcimb.2023.1103919] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/30/2023] [Indexed: 02/25/2023] Open
Abstract
Background The transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD. Method We recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits. Result Compared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05). Conclusion Our findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.
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Affiliation(s)
- Li He
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Bao-Zhu Yang
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States
| | - Yue-Jiao Ma
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Li Wen
- Department of Internal Medicine, Section of Endocrinology & Core Laboratory of Yale Center for Clinical Investigation, Yale University School of Medicine, New Haven, CT, United States
| | - Feng Liu
- Compulsory Detoxification Center of Changsha Public Security Bureau, Changsha, Hunan, China
| | - Xiao-Jie Zhang
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Tie-Qiao Liu
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
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Abstract
The occurrence and progression of colorectal cancer (CRC) are closely related to intestinal microecological disorders. Butyrate, the representative of short chain fatty acids, possess anti-inflammatory and antioxidant effects, and its antitumor effect has been gradually paid attention to. In this study, azoxymethane/dextran sodium sulfate induced mouse CRC model was used to explore the role and mechanism of butyrate in regulating colon cancer and its intestinal microecological balance. Outcomes exhibited that butyrate alleviated weight loss, disease activity index, and survival in CRC mice and inhibited tumor number and progression. Further research revealed that butyrate restrained the aggregation of harmful while promoting the colonization of beneficial flora, such as Actinobacteriota, Bifidobacteriales and Muribaculacea through 16S rDNA sequence analysis. This study confirmed that butyrate can ameliorate CRC by repairing intestinal microecology, providing ideas and evidence for chemical prophylactic agents, such as butyrate to remedy tumors and regulate tumor microbiota.
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Xu S, Lv Q, Zou N, Zhang Y, Zhang J, Tang Q, Chou SH, Lu L, He J. Influence of neo-adjuvant radiotherapy on the intestinal microbiota of rectal cancer patients. J Cancer Res Clin Oncol 2023:10.1007/s00432-022-04553-6. [PMID: 36656381 DOI: 10.1007/s00432-022-04553-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 12/21/2022] [Indexed: 01/20/2023]
Abstract
PURPOSE Neo-adjuvant radiotherapy (NART) is a widely used pre-surgery radiotherapy for rectal cancer patients. Although NART is effective in reducing tumor burden before surgery, it may cause dysbiosis of intestinal microbiota. The intestinal microbiota shapes tumor inflammatory environment and influences cancer progression. However, how NART remodels the microbiota and how the microbiota affects therapeutic efficacy has been largely elusive. This study aimed to reveal the details of how NART affects the intestinal microbiota in patients with rectal cancer. METHODS Rectal cancer patients who received NART were recruited into the study, and their healthy family members on the same diet served as controls. Stool samples from five rectal cancer patients (28 in total) and five healthy individuals (16 in total) were collected for intestinal microbiota analysis by 16S rRNA gene amplicon sequencing. Samples from patients were divided into earlier- and later-NART according to the number of NART. RESULTS NART did not significantly affect the α diversity of intestinal microbiota. However, the abundance of bacterial genera associated with cancer progression tended to decrease in later-NART patients. More importantly, a variety of oral pathogenic bacteria were enriched in the intestine of later-NART patients. NART also affected functional pathways associated with the microbiota in DNA repair, metabolism, and bacterial infection. CONCLUSION NART significantly altered the microbiota composition and function in rectal cancer patients, and some oral pathogens were found to translocate to the intestine. This is the first report to study the effect of NART on intestinal microbiota in patients with rectal cancer, exploring the importance of intestinal microbiota during the process of NART.
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Affiliation(s)
- Siyang Xu
- State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Qimei Lv
- State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Ning Zou
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, People's Republic of China
| | - Yuling Zhang
- State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Jiucheng Zhang
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, People's Republic of China
| | - Qing Tang
- State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Shan-Ho Chou
- State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Li Lu
- Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, People's Republic of China.
| | - Jin He
- State Key Laboratory of Agricultural Microbiology & Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.
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Bucher-Johannessen C, Birkeland EE, Vinberg E, Bemanian V, Hoff G, Berstad P, Rounge TB. Long-term follow-up of colorectal cancer screening attendees identifies differences in Phascolarctobacterium spp. using 16S rRNA and metagenome sequencing. Front Oncol 2023; 13:1183039. [PMID: 37182146 PMCID: PMC10172651 DOI: 10.3389/fonc.2023.1183039] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 03/31/2023] [Indexed: 05/16/2023] Open
Abstract
Background The microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross-sectional studies. However, there is a lack of studies using prospectively collected samples. Methods From the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the samples and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity and differential abundance. Results Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was associated with time to CRC diagnosis. Conclusion Using a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.
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Affiliation(s)
- Cecilie Bucher-Johannessen
- Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway
| | | | - Elina Vinberg
- Department of Research, Cancer Registry of Norway, Oslo, Norway
| | - Vahid Bemanian
- Department of Pathology, Akershus University Hospital, Oslo, Norway
| | - Geir Hoff
- Department of Research, Telemark Hospital Skien, Skien, Norway
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo University Hospital, Oslo, Norway
| | - Paula Berstad
- Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo University Hospital, Oslo, Norway
| | - Trine B. Rounge
- Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Centre for Bioinformatics, Department of Pharmacy, University of Oslo, Oslo, Norway
- *Correspondence: Trine B. Rounge,
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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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Abstract
The gut microbiota (GM) is associated with colorectal cancer (CRC) development. However, studies demonstrating the role of GM in CRC are limited to metagenomic analyses. These studies lack direct evidence proving that the candidate strains are involved in CRC, and isolated probiotics for bacteriotherapy. Therefore, to identify novel GM with anti-CRC activity, we previously isolated gut bacteria from the feces of healthy individuals, screened the isolated GM's anti-CRC activity, and discovered that cell-free supernatants of GM isolates demonstrated antiproliferative activity against CRC cells. Here, our study identified one of them as Eubacterium callanderi and chose it for further study because the genus Eubacterium has been suggested to contribute to various aspects of gut health; however, the functions are unknown. First, we confirmed that E. callanderi cell-free supernatant (EcCFS) exerted antiproliferative activity-by inducing apoptosis and cell cycle arrest-that was dose-dependent and specific to cancer cell lines. Next, we discovered that EcCFS active molecules were heat stable and protease insensitive. High-performance liquid chromatography analysis revealed that EcCFS contained high butyrate concentrations possessing anticancer activity. Additionally, gas chromatography-mass spectrometry analysis of the aqueous phase of ethyl acetate-extracted EcCFS and an antiproliferation assay of the aqueous phase and 4-aminobutanoic acid (GABA) suggested that GABA is a possible anti-CRC agent. Finally, in the CT26 allograft mouse model, E. callanderi oral administration and EcCFS peri-tumoral injection inhibited tumor growth in vivo. Therefore, our study reveals that E. callanderi has an anti-CRC effect and suggests that it may be a potential candidate for developing probiotics to control CRC. IMPORTANCE The gut microbiota has been reported to be involved in colorectal cancer, as suggested by metagenomic analysis. However, metagenomic analysis has limitations, such as bias in the analysis and the absence of bacterial resources for follow-up studies. Therefore, we attempted to discover gut microorganisms that are related to colorectal cancer using the culturomics method. In this study, we discovered that Eubacterium callanderi possesses anti-colorectal cancer activity in vitro and in vivo, suggesting that E. callanderi could be used in bacteriotherapy for colorectal cancer treatment.
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Jacobs JP, Goudarzi M, Lagishetty V, Li D, Mak T, Tong M, Ruegger P, Haritunians T, Landers C, Fleshner P, Vasiliauskas E, Ippoliti A, Melmed G, Shih D, Targan S, Borneman J, Fornace AJ, McGovern DPB, Braun J. Crohn's disease in endoscopic remission, obesity, and cases of high genetic risk demonstrates overlapping shifts in the colonic mucosal-luminal interface microbiome. Genome Med 2022; 14:91. [PMID: 35971134 PMCID: PMC9377146 DOI: 10.1186/s13073-022-01099-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 08/02/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Crohn's disease (CD) patients demonstrate distinct intestinal microbial compositions and metabolic characteristics compared to unaffected controls. However, the impact of inflammation and underlying genetic risk on these microbial profiles and their relationship to disease phenotype are unclear. We used lavage sampling to characterize the colonic mucosal-luminal interface (MLI) microbiome of CD patients in endoscopic remission and unaffected controls relative to obesity, disease genetics, and phenotype. METHODS Cecum and sigmoid colon were sampled from 110 non-CD controls undergoing screening colonoscopy who were stratified by body mass index and 88 CD patients in endoscopic remission (396 total samples). CD polygenic risk score (GRS) was calculated using 186 known CD variants. MLI pellets were analyzed by 16S ribosomal RNA gene sequencing, and supernatants by untargeted liquid chromatography-mass spectrometry. RESULTS CD and obesity were each associated with decreased cecal and sigmoid MLI bacterial diversity and distinct bacterial composition compared to controls, including expansion of Escherichia/Shigella. Cecal and sigmoid dysbiosis indices for CD were significantly greater in obese controls than non-overweight controls. CD, but not obesity, was characterized by altered biogeographic relationship between the sigmoid and cecum. GRS was associated with select taxonomic shifts that overlapped with changes seen in CD compared to controls including Fusobacterium enrichment. Stricturing or penetrating Crohn's disease behavior was characterized by lower MLI bacterial diversity and altered composition, including reduced Faecalibacterium, compared to uncomplicated CD. Taxonomic profiles including reduced Parasutterella were associated with clinical disease progression over a mean follow-up of 3.7 years. Random forest classifiers using MLI bacterial abundances could distinguish disease state (area under the curve (AUC) 0.93), stricturing or penetrating Crohn's disease behavior (AUC 0.82), and future clinical disease progression (AUC 0.74). CD patients showed alterations in the MLI metabolome including increased cholate:deoxycholate ratio compared to controls. CONCLUSIONS Obesity, CD in endoscopic remission, and high CD genetic risk have overlapping colonic mucosal-luminal interface (MLI) microbiome features, suggesting a shared microbiome contribution to CD and obesity which may be influenced by genetic factors. Microbial profiling during endoscopic remission predicted Crohn's disease behavior and progression, supporting that MLI sampling could offer unique insight into CD pathogenesis and provide novel prognostic biomarkers.
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Affiliation(s)
- Jonathan P Jacobs
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-6949, USA.
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, USA.
| | | | - Venu Lagishetty
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-6949, USA
| | - Dalin Li
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Tytus Mak
- National Institute of Standards and Technology, Gaithersburg, USA
| | - Maomeng Tong
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, USA
| | - Paul Ruegger
- Department of Plant Pathology and Microbiology, University of California Riverside, Riverside, USA
| | - Talin Haritunians
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Carol Landers
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Philip Fleshner
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Eric Vasiliauskas
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Andrew Ippoliti
- Department of Medicine, Keck School of Medicine of USC, Los Angeles, USA
| | - Gil Melmed
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - David Shih
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Stephan Targan
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - James Borneman
- Department of Plant Pathology and Microbiology, University of California Riverside, Riverside, USA
| | - Albert J Fornace
- Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, USA
| | - Dermot P B McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Jonathan Braun
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, USA
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The Tissue-Associated Microbiota in Colorectal Cancer: A Systematic Review. Cancers (Basel) 2022; 14:cancers14143385. [PMID: 35884445 PMCID: PMC9317273 DOI: 10.3390/cancers14143385] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 07/05/2022] [Accepted: 07/08/2022] [Indexed: 11/28/2022] Open
Abstract
Simple Summary Growing evidence shows a close relationship between the microbiome and colorectal cancer, but most studies analyze fecal samples. However, solid information on the microbial community that is present locally in the intestinal tumor tissues is lacking. Therefore, the aim of this systematic review was to compile evidence on the relationship between tissue-associated microbiota and colorectal cancer. Among 5080 screened publications, 39 were eligible and included in the analysis. Despite the heterogeneity in methodologies and reporting between studies, 12 groups of bacteria with strong positive and 18 groups of bacteria with strong negative associations with colorectal cancer were identified. Such knowledge may ultimately be used in novel strategies that aim to prevent, detect, and treat colorectal cancer in the upcoming years. Abstract The intestinal microbiome is associated with colorectal cancer. Although the mucosal microbiota better represents an individual’s local microbiome, studies on the colorectal cancer microbiota mainly reflect knowledge obtained from fecal samples. This systematic review aimed to summarize the current evidence on the relationship between the mucosal-associated bacterial microbiota and colorectal cancer. Searches were conducted in PubMed and Web of Science databases for publications comparing the mucosal microbiome of colorectal cancer patients with that of healthy controls, or with that of non-cancerous mucosal tissues. The primary outcomes were differences in microbial diversity and taxonomy. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Of the 5080 studies identified, 39 were eligible and included in the systematic review. No consistent results were identified for the α- and β-diversity, due to high heterogeneity in reporting and to differences in metrics and statistical approaches, limiting study comparability. Qualitative synthesis of microbial taxonomy identified 12 taxa with strong positive and 18 taxa with strong negative associations with colorectal cancer. Fusobacterium, Campylobacter, Parvimonas, Peptostreptococcus, Streptococcus, and Granulicatella were defined as enriched in colorectal cancer. Despite the methodological limitations of the studies, consistent evidence on bacterial taxa associated with colorectal cancer was identified. Prospective studies in large and well-characterized patient populations will be crucial to validate these findings.
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Merino-Ribas A, Araujo R, Pereira L, Campos J, Barreiros L, Segundo MA, Silva N, Costa CFFA, Quelhas-Santos J, Trindade F, Falcão-Pires I, Alencastre I, Dumitrescu IB, Sampaio-Maia B. Vascular Calcification and the Gut and Blood Microbiome in Chronic Kidney Disease Patients on Peritoneal Dialysis: A Pilot Study. Biomolecules 2022; 12:biom12070867. [PMID: 35883423 PMCID: PMC9313079 DOI: 10.3390/biom12070867] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/08/2022] [Accepted: 06/16/2022] [Indexed: 12/13/2022] Open
Abstract
Vascular calcification (VC) is a frequent condition in chronic kidney disease (CKD) and a well-established risk factor for the development of cardiovascular disease (CVD). Gut dysbiosis may contribute to CVD and inflammation in CKD patients. Nonetheless, the role of gut and blood microbiomes in CKD-associated VC remains unknown. Therefore, this pilot study aimed to explore the link between gut and blood microbiomes and VC in CKD patients on peritoneal dialysis (CKD-PD). Our results showed relative changes in specific taxa between CKD-PD patients with and without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, and Eubacterium eligens group in the gut, and Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, and Pelomonas in the blood. An association between VC and all-cause mortality risk in CKD-PD patients was also observed, and patients with higher mortality risk corroborate the changes of Eubacterium eligens in the gut and Devosia genus in the blood. Although we did not find differences in uremic toxins, intestinal translocation markers, and inflammatory parameters among CKD-PD patients with and without VC, soluble CD14 (sCD14), a nonspecific marker of monocyte activation, positively correlated with VC severity. Therefore, gut Eubacterium eligens group, blood Devosia, and circulating sCD14 should be further explored as biomarkers for VC, CVD, and mortality risk in CKD.
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Affiliation(s)
- Ana Merino-Ribas
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
- Departament de Medicina, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain;
- Nephrology Department, Hospital Universitari de Girona Doctor Josep Trueta, 17007 Girona, Spain
| | - Ricardo Araujo
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
| | - Luciano Pereira
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
- Nephrology Department, Centro Hospitalar Universitário de São João, 4200-319 Porto, Portugal;
| | - Joana Campos
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
| | - Luísa Barreiros
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (L.B.); (M.A.S.)
| | - Marcela A. Segundo
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (L.B.); (M.A.S.)
| | - Nádia Silva
- Nephrology Department, Centro Hospitalar Universitário de São João, 4200-319 Porto, Portugal;
| | - Carolina F. F. A. Costa
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
| | - Janete Quelhas-Santos
- UnIC@RISE- Cardiovascular Research and Development Centre, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.Q.-S.); (F.T.); (I.F.-P.)
| | - Fábio Trindade
- UnIC@RISE- Cardiovascular Research and Development Centre, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.Q.-S.); (F.T.); (I.F.-P.)
| | - Inês Falcão-Pires
- UnIC@RISE- Cardiovascular Research and Development Centre, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.Q.-S.); (F.T.); (I.F.-P.)
| | - Ines Alencastre
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
| | - Ioana Bancu Dumitrescu
- Departament de Medicina, Universitat Autonoma de Barcelona, 08035 Barcelona, Spain;
- Fresenius Nephrocare, 110372 Pitesti, Romania
| | - Benedita Sampaio-Maia
- Nephrology & Infectious Diseases R & D Group, i3S—Instituto de Investigação e Inovação em Saúde, INEB—Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal; (A.M.-R.); (R.A.); (L.P.); (J.C.); (C.F.F.A.C.); (I.A.)
- Faculdade de Medicina Dentária, Universidade do Porto, 4200-393 Porto, Portugal
- Correspondence: ; Tel.: +351-220-901-100
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22
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Chen H, Ye C, Cai B, Zhang F, Wang X, Zhang J, Zhang Z, Guo Y, Yao Q. Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota. BMC Cancer 2022; 22:566. [PMID: 35596224 PMCID: PMC9123795 DOI: 10.1186/s12885-022-09635-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 05/04/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The role of Berberine (BBR) in colorectal cancer (CRC) and gut microbiota has begun to appreciate. However, there was no direct evidence confirm that the gut microbiota regulated by BBR could inhibit CRC. This report investigated the effect of stool from BBR treated subjects and its effect on CRC. METHODS A mouse model for CRC was developed using azoxymethane (AOM) and dextran sulfate sodium (DSS). Intestinal tissue from affected mice were used to determine the efficacy of BBR against CRC. Stool samples were collected for the 16s rRNA gene sequencing and fecal microbiota transplantation (FMT). Finally, the mechanism of gut microbiota from BBR treated mice on CRC was explored using immunohistochemistry, RNA-Sequencing, quantitative RT-PCR, and western blot analyses. RESULTS BBR significantly reduced intestinal tumor development. The richness of gut microbiota were notably decreased by BBR. Specifically, the relative abundance of beneficial bacteria (Roseburia, Eubacterium, Ruminococcaceae, and Firmicutes_unclassified) was increased while the level of bacteria (Odoribacter, Muribaculum, Mucispirillum, and Parasutterella) was decreased by BBR treatment. FMT experiment determined that the mice fed with stool from BBR treated AOM/DSS mice demonstrated a relatively lower abundance of macroscopic polyps and a significantly lower expression of β-catenin, and PCNA in intestinal tissue than mice fed with stool from AOM/DSS mice. Mechanistically, intestinal tissue obtained from mice fed with stool from BBR treated AOM/DSS mice demonstrated a decreased expression of inflammatory cytokines including interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), C-C motif chemokine 1 (Ccl1), Ccl6, and C-X-C motif ligand (Cxcl9). In addition, the NF-κB expression was greatly suppressed in mice fed with stool from BBR treated AOM/DSS mice. Real-time PCR arrays revealed a down-regulation of genes involved in cell proliferation, angiogenesis, invasiveness, and metastasis in mice fed with stool from BBR treated AOM/DSS mice. CONCLUSIONS Stool obtained from BBR treated AOM/DSS mice was able to increase colon length while simultaneously decreasing the density of macroscopic polyps, cell proliferation, inflammatory modulators and the expression of NF-κB. Therefore, it was concluded that suppression of pro-inflammatory genes and carcinogens factors by modulating gut microbiota was an important pathway for BBR to inhibit tumor growth in conventional mice.
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Affiliation(s)
- Haitao Chen
- Department of Integrated Chinese and Western Medicine, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China
| | - Chenxiao Ye
- Zhejiang Chinese Medical University, 310053, Hangzhou, Zhejiang, China
| | - Biyu Cai
- Zhejiang Chinese Medical University, 310053, Hangzhou, Zhejiang, China
| | - Fan Zhang
- Zhejiang Chinese Medical University, 310053, Hangzhou, Zhejiang, China
| | - Xuanying Wang
- Zhejiang Chinese Medical University, 310053, Hangzhou, Zhejiang, China
| | - Jin Zhang
- Zhejiang Chinese Medical University, 310053, Hangzhou, Zhejiang, China
| | - Zewei Zhang
- Department of Abdominal Surgical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, Hangzhou, Zhejiang, China
| | - Yong Guo
- Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310003, Hangzhou, Zhejiang, China.
| | - Qinghua Yao
- Department of Integrated Chinese and Western Medicine, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China. .,Key Laboratory of Traditional Chinese Medicine Oncology, Zhejiang Cancer Hospital, 310022, Hangzhou, China. .,Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, 310022, Hangzhou, Zhejiang, China.
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23
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Grochowska M, Perlejewski K, Laskus T, Radkowski M. The Role of Gut Microbiota in Gastrointestinal Tract Cancers. Arch Immunol Ther Exp (Warsz) 2022; 70:7. [PMID: 35112169 PMCID: PMC8810472 DOI: 10.1007/s00005-021-00641-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
Disturbances in gastrointestinal (GI) microbiota could play a significant role in the development of GI cancers, but the underlying mechanisms remain largely unclear. While some bacteria seem to facilitate carcinogenesis, others appear to be protective. So far only one bacterium (Helicobacter pylori) has been classified by the International Agency for Cancer Research as carcinogenic in humans but many other are the subject of intense research. Most studies on the role of microbiota in GI tract oncogenesis focus on pancreatic and colorectal cancers with the following three species: Helicobacter pylori, Escherichia coli, and Porphyromonas gingivalis as likely causative factors. This review summarizes the role of bacteria in GI tract oncogenesis.
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Affiliation(s)
- Marta Grochowska
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Karol Perlejewski
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Tomasz Laskus
- Department of Adult Infectious Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Marek Radkowski
- Department of Immunopathology, Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland
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24
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Zhang M, Lv Y, Hou S, Liu Y, Wang Y, Wan X. Differential Mucosal Microbiome Profiles across Stages of Human Colorectal Cancer. Life (Basel) 2021; 11:831. [PMID: 34440574 PMCID: PMC8401903 DOI: 10.3390/life11080831] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 08/12/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Emerging evidences link gut microbiota to colorectal cancer (CRC) initiation and development. However, the CRC stage- and spatial-specific bacterial taxa were less investigated, especially in a Chinese cohort, leading to our incomplete understanding of the functional roles of gut microbiota in promoting CRC progression and recurrence. Here, we report the composition and structure of gut microbiota across CRC stages I, II and III, by analyzing the gut mucosal microbiomes of 75 triplet-paired samples collected from on-tumor, adjacent-tumor and off-tumor sites and 26 healthy controls. We observed tumor-specific pattern of mucosal microbiome profiles as CRC progressed and identified ten bacterial taxa with high abundances (>1%) as potential biomarkers for tumor initiation and development. Peptostreptococcus and Parvimonas can serve as biomarkers for CRC stage I. Fusobacterium, Streptococcus, Parvimonas, Burkholderiales, Caulobacteraceae, Delftia and Oxalobacteraceae can serve as biomarkers for CRC stage II, while Fusobacterium, Burkholderiales, Caulobacteraceae, Oxalobacteraceae, Faecalibacterium and Sutterella can serve as biomarkers for CRC stage III. These biomarkers classified CRC stages I, II and III distinguished from each other with an area under the receiver-operating curve (AUC) > 0.5. Moreover, co-occurrence and co-excluding network analysis of these genera showed strong correlations in CRC stage I, which were subsequently reduced in CRC stages II and III. Our findings provide a reference index for stage-specific CRC diagnosis and suggest stage-specific roles of Peptostreptococcus, Fusobacterium, Streptococcus and Parvimonas in driving CRC progression.
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Affiliation(s)
- Mingqing Zhang
- Nankai University School of Medicine, Nankai University, Tianjin 300071, China;
- Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; (Y.L.); (Y.L.)
| | - Yongming Lv
- Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; (Y.L.); (Y.L.)
| | - Shaobin Hou
- Advanced Studies in Genomics, Proteomics and Bioinformatics, University of Hawaii, Honolulu, HI 96822, USA;
| | - Yanfei Liu
- Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; (Y.L.); (Y.L.)
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yijia Wang
- Tianjin Union Medical Center, Nankai University, Tianjin 300121, China; (Y.L.); (Y.L.)
| | - Xuehua Wan
- TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300071, China
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25
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Fang CY, Chen JS, Hsu BM, Hussain B, Rathod J, Lee KH. Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers. Microorganisms 2021; 9:microorganisms9081548. [PMID: 34442626 PMCID: PMC8401100 DOI: 10.3390/microorganisms9081548] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/15/2021] [Accepted: 07/18/2021] [Indexed: 12/12/2022] Open
Abstract
Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.
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Affiliation(s)
- Chuan-Yin Fang
- Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 621, Taiwan;
| | - Jung-Sheng Chen
- Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan;
| | - Bing-Mu Hsu
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan;
- Center for Innovative on Aging Society (CIRAS), National Chung Cheng University, Chiayi 621, Taiwan
- Correspondence: ; Tel.: +886-52720411 (ext. 66218)
| | - Bashir Hussain
- Department of Earth and Environmental Sciences, National Chung Cheng University, Chiayi 621, Taiwan;
- Department of Biomedical Sciences, National Chung Cheng University, Chiayi 621, Taiwan
| | - Jagat Rathod
- Department of Earth Sciences, National Cheng Kung University, Tainan 701, Taiwan;
| | - Kuo-Hsin Lee
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan;
- School of Medicine, I-Shou University, Kaohsiung 824, Taiwan
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26
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González-Mercado VJ, Lim J, Marrero S, Pedro E, Saligan LN. Gut microbiota and fatigue in rectal cancer patients: a cross-sectional pilot study. Support Care Cancer 2021; 29:4615-4621. [PMID: 33495850 DOI: 10.1007/s00520-021-06013-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 01/19/2021] [Indexed: 12/17/2022]
Abstract
CONTEXT Although microbial-mediated disturbance of intestinal mucosal homeostasis (dysbiosis) is believed to contribute to the pathogenesis of chemotherapy and radiotherapy (CRT)-related fatigue, potential differences in the gut microbial diversity and in the abundance of gut microbial taxa between fatigued and non-fatigued patients have not been adequately examined, particularly in the rectal cancer population. PURPOSE In this cross-sectional study, we aim to examine the differences in (a) gut microbial diversity and gut microbial abundances and (b) predicted functional pathways of the gut microbiome between rectal cancer participants with and without fatigue at the end of CRT. METHODS Rectal cancer patients (n = 50) provided stool samples for 16S rRNA gene sequencing and symptom ratings for fatigue at the end of CRT. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. RESULTS Fatigued (n = 35) participants showed enriched bacterial abundances of Eubacterium, Streptococcus, Adlercreutzia, and Actinomyces, as well as enriched abundances of the microbial sucrose degradation pathway, compared to non-fatigued patients at the end of CRT (n = 15). CONCLUSIONS Differentially abundant microbial taxa were identified in fatigued and non-fatigued rectal cancer participants at the end of CRT. However, the exact role of these taxa (and identification of species) in the biology of CRT-related fatigue remains to be examined.
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Affiliation(s)
| | - Jean Lim
- University of Miami, Miami, FL, USA
| | - Sara Marrero
- College of Arts and Sciences, University of South Florida, Tampa, FL, USA
| | - Elsa Pedro
- School of Pharmacy, Medical Science Campus, University of Puerto Rico, San Juan, Puerto Rico
| | - Leorey N Saligan
- Symptom Science Center, Principal Investigator, Symptom Biology Unit, Division of Intramural Research, NINR, NIH, DHHS, Bethesda, MD, USA
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27
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Wang Y, Wan X, Wu X, Zhang C, Liu J, Hou S. Eubacterium rectale contributes to colorectal cancer initiation via promoting colitis. Gut Pathog 2021; 13:2. [PMID: 33436075 PMCID: PMC7805161 DOI: 10.1186/s13099-020-00396-z] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The 'driver-passenger' model in human gut microbial dysbiosis suggests that 'driver' bacteria may colonize with low relative abundance on tumor site but persistently induce chronic change in normal intestinal epithelium and initiate CRC. They are gradually replaced by 'passenger' bacteria later on, due to their low adaptability to the on-tumor site niche. RESULTS To reveal site-specific bacterial taxon markers in CRC patients, we analyzed the gut mucosal microbiome of 75 paired samples of on-tumor and tumor-adjacent sites, 75 off-tumor sites, and 26 healthy controls. Linear discriminant analysis of relative abundance profiles revealed unique bacterial taxon distribution correlated with specific tumor sites, with Eubacterium having the distribution characteristic of potential driver bacteria. We further show that Eubacterium rectale endotoxin activates the transcription factor NF-κΒ, which regulates multiple aspects of innate and adaptive immune responses in normal colon epithelial cells. Unlike the 'passenger' bacterium Fusobacterium nucleatum, E. rectale promotes dextran sodium sulfate-induced colitis in Balb/c mice. CONCLUSIONS Our findings reveal that E. rectale functions as a 'driver' bacterium and contributes to cancer initiation via promoting inflammation.
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Affiliation(s)
- Yijia Wang
- Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Rd., Hongqiao district, Tianjin, 300121, China
| | - Xuehua Wan
- TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin, 300071, China
| | - Xiaojing Wu
- Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Rd., Hongqiao district, Tianjin, 300121, China
| | - Chunze Zhang
- Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Rd., Hongqiao district, Tianjin, 300121, China
| | - Jun Liu
- Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Rd., Hongqiao district, Tianjin, 300121, China.
| | - Shaobin Hou
- Advanced Studies in Genomics, Proteomics, and Bioinformatics, University of Hawaii At Manoa, 2538 McCarthy Mall, Snyder Hall, Honolulu, HI, 96822, USA.
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28
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Fattahi Y, Heidari HR, Khosroushahi AY. Review of short-chain fatty acids effects on the immune system and cancer. FOOD BIOSCI 2020. [DOI: 10.1016/j.fbio.2020.100793] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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The Effects of Prebiotic Supplementation with OMNi-LOGiC ® FIBRE on Fecal Microbiome, Fecal Volatile Organic Compounds, and Gut Permeability in Murine Neuroblastoma-Induced Tumor-Associated Cachexia. Nutrients 2020; 12:nu12072029. [PMID: 32650568 PMCID: PMC7400931 DOI: 10.3390/nu12072029] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 06/26/2020] [Accepted: 07/04/2020] [Indexed: 02/06/2023] Open
Abstract
Malignant diseases can cause tumor-associated cachexia (TAC). Supplementation with prebiotic non-digestible carbohydrates exerts positive metabolic effects in experimental oncologic diseases. The aim of this project was to assess the effect of prebiotic supplementation with OMNi-LOGiC® FIBRE on intestinal microbiome, bacterial metabolism, gut permeability, and inflammation in a murine model of neuroblastoma (NB)-associated TAC. For this study, 2,000,000 NB cells (MHH-NB11) were implanted into athymic mice followed by daily supplementation with water or 200 mg prebiotic oligosaccharide (POS) OMNi-LOGiC® FIBRE (NB-Aqua, n = 12; NB-POS, n = 12). Three animals of each tumor group did not develop NB. The median time of tumor growth (first visibility to euthanasia) was 37 days (IQR 12.5 days) in the NB-Aqua group and 37 days (IQR 36.5 days) in the NB-POS group (p = 0.791). At euthanasia, fecal microbiome and volatile organic compounds (VOCs), gut permeability (fluorescein isothiocyanate-dextran (FITC-dextran), and gut barrier markers were measured. Values were compared to sham animals following injection of culture medium and gavage of either water or OMNi-LOGiC® FIBRE (SH-Aqua, n = 10; SH-POS, n = 10). Alpha diversity did not differ significantly between the groups. Principal coordinate analysis (PCoA) revealed clustering differences between Aqua and POS animals. Both NB and POS supplementation led to taxonomic alterations of the fecal microbiome. Of 49 VOCs, 22 showed significant differences between the groups. NB animals had significantly higher gut permeability than Aqua animals; POS did not ameliorate these changes. The pore and leak pathways of tight junctions did not differ between groups. In conclusion, our results suggest that NB-induced TAC causes increased gut permeability coupled with compositional changes in the fecal microbiome and VOC profile. Prebiotic supplementation with OMNi-LOGiC® FIBRE seemed to induce modifications of the fecal microbiome and VOC profile but did not improve gut permeability.
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30
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Wang W, Fang D, Zhang H, Xue J, Wangchuk D, Du J, Jiang L. Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1. Onco Targets Ther 2020; 13:4691-4704. [PMID: 32547098 PMCID: PMC7263851 DOI: 10.2147/ott.s235575] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 05/07/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Sodium butyrate (NaB) is a short-chain fatty acid which is produced by bacterial fermentation of nondigestible dietary fiber and has been reported to exert anti-tumor effects in many tumors including colorectal cancer (CRC). However, the role of thioredoxin-1 (Trx-1) in NaB-induced anti-tumor effect has not been completely clarified. MATERIALS AND METHODS Effects of NaB on the growth of CRC cell lines HT29 and SW480 were detected by the Cell Counting Kit-8 (CCK-8) and colony formation assays. The apoptotic cells were determined by flow cytometry, and cell migration was assessed by a Transwell assay. Western blot analysis was used to test the Trx-1 and epithelial-to-mesenchymal transition (EMT)-related proteins level. Reactive oxygen species (ROS) level was determined and N-acetylcysteine (NAC) recovery experiment was performed in CRC cells. In addition, mice xenograft model was established to test the effect of NaB on CRC growth in vivo. Further, the effects of NaB on CRC cells with overexpression or knockdown were tested by the CCK-8 and Transwell assays. RESULTS NaB treatment significantly inhibited cell growth and decreased Trx-1 protein expression in CRC cells but not in normal colon epithelial cells. NaB also induced apoptosis, inhibited colony formation, migration and EMT in CRC cells. Besides, NaB increased ROS level in CRC cells and NAC reversed NaB-induced inhibition of cell proliferation. Moreover, downregulation of Trx-1 significantly enhanced NaB-induced inhibitory effects on cell growth and migration, whereas overexpression of Trx-1 attenuated NaB-induced inhibitory effects on growth and migration in CRC cells. CONCLUSION These findings indicate that the NaB-mediated anti-tumor effects on CRC cells are related to downregulation of Trx-1.
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Affiliation(s)
- Wenqi Wang
- Department of Microbiology and Immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou325000, People’s Republic of China
- Department of Laboratory Medicine, Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital, Shanghai 201318, People’s Republic of China
| | - Daoquan Fang
- Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou325000, People’s Republic of China
| | - Hao Zhang
- Department of Microbiology and Immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou325000, People’s Republic of China
| | - Jiao Xue
- Department of Microbiology and Immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou325000, People’s Republic of China
| | - Drugyel Wangchuk
- Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou325000, People’s Republic of China
| | - Jimei Du
- Department of Microbiology and Immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou325000, People’s Republic of China
| | - Lei Jiang
- Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou325000, People’s Republic of China
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Xu S, Yin W, Zhang Y, Lv Q, Yang Y, He J. Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer. Cancers (Basel) 2020; 12:cancers12020372. [PMID: 32041122 PMCID: PMC7072156 DOI: 10.3390/cancers12020372] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 02/03/2020] [Accepted: 02/04/2020] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third cause of cancer death in the world, while intestinal microbiota is a community of microbes living in human intestine that can potentially impact human health in many ways. Accumulating evidence suggests that intestinal microbiota, especially that from the intestinal bacteria, play a key role in the CRC development; therefore, identification of bacteria involved in CRC development can provide new targets for the CRC diagnosis, prevention, and treatment. Over the past decade, there have been considerable advances in applying 16S rDNA sequencing data to verify associated intestinal bacteria in CRC patients; however, due to variations of individual and environment factors, these results seem to be inconsistent. In this review, we scrutinized the previous 16S rDNA sequencing data of intestinal bacteria from CRC patients, and identified twelve genera that are specifically enriched in the tumor microenvironment. We have focused on their relationship with the CRC development, and shown that some bacteria could promote CRC development, acting as foes, while others could inhibit CRC development, serving as friends, for human health. Finally, we highlighted their potential applications for the CRC diagnosis, prevention, and treatment.
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Kang Y, Feng D, Law HKW, Qu W, Wu Y, Zhu GH, Huang WY. Compositional alterations of gut microbiota in children with primary nephrotic syndrome after initial therapy. BMC Nephrol 2019; 20:434. [PMID: 31771550 PMCID: PMC6878711 DOI: 10.1186/s12882-019-1615-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Accepted: 11/06/2019] [Indexed: 02/08/2023] Open
Abstract
Background Primary nephrotic syndrome (PNS) is a common glomerular disease in children. T cell dysfunction plays a crucial role in the pathogenesis of PNS. Moreover, dysbiosis of gut microbiota contributes to immunological disorders. Whether the initial therapy of PNS affects gut microbiota remains an important question. Our study investigated compositional changes of gut microbiota after initial therapy. Methods Fecal samples of 20 children with PNS were collected before and after 4-week initial therapy. Total bacteria DNA were extracted and the V3-V4 regions of bacteria 16S ribosomal RNA gene were sequenced. The composition of gut microbiota before and after initial therapy was analyzed by bioinformatics methods. The function of altered gut microbiota was predicted with PICRUSt method. Results The richness and diversity of gut microbiota were similar before and after 4-week initial therapy. Gut microbiota at the phylum level was dominated by four phyla including Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria, but the increased relative abundance after initial therapy was found in Deinococcus-Thermus and Acidobacteria. At the genus level, the increased abundance of gut microbiota after initial therapy was observed in short chain fat acids (SCFA)-producing bacteria including Romboutsia, Stomatobaculum and Cloacibacillus (p < 0.05). Moreover, the predicted functional profile of gut microbiota showed that selenocompound metabolism, isoflavonoid biosynthesis and phosphatidylinositol signaling system weakened after initial therapy of PNS. Conclusions Initial therapy of PNS increased SCFA-producing gut microbiota, but might diminish selenocompound metabolism, isoflavonoid biosynthesis and phosphatidylinositol signaling system in children.
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Affiliation(s)
- Yulin Kang
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China
| | - Dan Feng
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China
| | - Helen Ka-Wai Law
- Department of Health Technology and Informatics, Faculty of Health and Social Science, Hong Kong Polytechnic University, Hunghom, Hong Kong, China
| | - Wei Qu
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China
| | - Ying Wu
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China
| | - Guang-Hua Zhu
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China
| | - Wen-Yan Huang
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.
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Mentella MC, Scaldaferri F, Ricci C, Gasbarrini A, Miggiano GAD. Cancer and Mediterranean Diet: A Review. Nutrients 2019; 11:E2059. [PMID: 31480794 PMCID: PMC6770822 DOI: 10.3390/nu11092059] [Citation(s) in RCA: 271] [Impact Index Per Article: 45.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 08/17/2019] [Accepted: 08/29/2019] [Indexed: 12/11/2022] Open
Abstract
The Mediterranean diet is considered one of the most worldwide healthy dietary patterns thanks to a combination of foods rich mainly in antioxidants and anti-inflammatory nutrients. Many studies have demonstrated a strong and inverse relationship between a high level of Mediterranean diet adherence and some chronic diseases (such as cardiovascular diseases, diabetes, etc.) and cancer. Given its protective effects in reducing oxidative and inflammatory processes of cells and avoiding DNA damages, cell proliferation, and their survival, angiogenesis, inflammations and metastasis, the Mediterranean diet is considered a powerful and manageable method to fight cancer incidence. The aim of this narrative review was to determine the magnitude of interaction between the Mediterranean diet and more widespread types of cancer so as to give a first and useful overview on this relationship identifying, with a nutritional approach, those nutrients of Mediterranean diet able to reduce cancer incidence.
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Affiliation(s)
- Maria Chiara Mentella
- UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
| | - Franco Scaldaferri
- UOC di Medicina Interna e Gastroenterologia, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Caterina Ricci
- UOC di Ginecologia Oncologica, Area Salute della Donna, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- UOC di Medicina Interna e Gastroenterologia, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giacinto Abele Donato Miggiano
- UOC di Nutrizione Clinica, Area Medicina Interna, Gastroenterologia e Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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