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Dovhalyuk V, Yang F, Nikolic S, Vujasinovic M, Löhr JM, Globisch D. Differences in the Fecal Metabolome of Autoimmune Pancreatitis Patients. United European Gastroenterol J 2025. [PMID: 40243134 DOI: 10.1002/ueg2.70025] [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: 09/08/2024] [Revised: 02/08/2025] [Accepted: 02/16/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Chronic pancreatitis is a risk factor for pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis that is primarily characterized by its immune mediate etiology, clinically resembling pancreatic cancer, yet uniquely responsive to steroid treatment. OBJECTIVE Early and accurate diagnosis of autoimmune pancreatitis is vital for effective treatment and patient prognosis, for which new diagnostic tools are urgently required. Gut microbiota dysbiosis has been identified to correlate with the development of pancreatic diseases, which provides new opportunities for the discovery of disease biomarkers. METHODS We utilized a mass spectrometric global metabolomics investigation of patient autoimmune pancreatitis and chronic pancreatitis fecal samples, investigating microbiome, dietary and human metabolism. RESULTS We discovered a series of newly identified metabolic signatures between both patient groups including enterolactone, 4-guanidinobutanoic acid, and methylthioadenosine sulfoxide. Additionally, the analysis revealed significant differences in several metabolic pathways such as fatty acids, alkaloids, amino acids and peptides. CONCLUSION Our observations provide novel insights into important metabolic human pathways and microbiome-derived metabolites to distinguish autoimmune pancreatitis from chronic pancreatitis. These findings reveal systemic metabolic responses and the identified metabolites may be developed into potential biomarkers for future diagnosis to distinguish between autoimmune pancreatitis and chronic pancreatitis.
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Affiliation(s)
- Vladyslav Dovhalyuk
- Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Fan Yang
- Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Sara Nikolic
- Department of Gastroenterology, Clinic of Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
- Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden
- Department for Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - J-Matthias Löhr
- Department for Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Daniel Globisch
- Department of Chemistry - BMC, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Guo X, Shao Y. Role of the oral-gut microbiota axis in pancreatic cancer: a new perspective on tumor pathophysiology, diagnosis, and treatment. Mol Med 2025; 31:103. [PMID: 40102723 PMCID: PMC11917121 DOI: 10.1186/s10020-025-01166-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 03/11/2025] [Indexed: 03/20/2025] Open
Abstract
Pancreatic cancer, one of the most lethal malignancies, remains challenging due to late diagnosis, aggressive progression, and therapeutic resistance. Recent advances have revealed the presence of intratumoral microbiota, predominantly originating from the oral and gut microbiomes, which play pivotal roles in pancreatic cancer pathogenesis. The dynamic interplay between oral and gut microbial communities, termed the "oral-gut microbiota axis," contributes multifacetedly to pancreatic ductal adenocarcinoma (PDAC). Microbial translocation via anatomical or circulatory routes establishes tumor-resident microbiota, driving oncogenesis through metabolic reprogramming, immune regulation, inhibition of apoptosis, chronic inflammation, and dysregulation of the cell cycle. Additionally, intratumoral microbiota promote chemoresistance and immune evasion, further complicating treatment outcomes. Emerging evidence highlights microbial signatures in saliva and fecal samples as promising non-invasive diagnostic biomarkers, while microbial diversity correlates with prognosis. Therapeutic strategies targeting this axis-such as antibiotics, probiotics, and engineered bacteria-demonstrate potential to enhance treatment efficacy. By integrating mechanisms of microbial influence on tumor biology, drug resistance, and therapeutic applications, the oral-gut microbiota axis emerges as a critical regulator of PDAC, offering novel perspectives for early detection, prognostic assessment, and microbiome-based therapeutic interventions.
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Affiliation(s)
- Xuanchi Guo
- School of Stomatology, Shandong University, No. 44-1 Wenhua West Road, Jinan City, Shandong Province, China.
| | - Yuhan Shao
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
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Chen X, Sun F, Wang X, Feng X, Aref AR, Tian Y, Ashrafizadeh M, Wu D. Inflammation, microbiota, and pancreatic cancer. Cancer Cell Int 2025; 25:62. [PMID: 39987122 PMCID: PMC11847367 DOI: 10.1186/s12935-025-03673-6] [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: 10/14/2024] [Accepted: 02/04/2025] [Indexed: 02/24/2025] Open
Abstract
Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life of people around the world. In spite of the advances in the treatment of PC, the overall survival of this disease in advanced stage is less than 12%. Moreover, PC cells have aggressive behaviour in proliferation and metastasis as well as capable of developing therapy resistance. Therefore, highlighting the underlying molecular mechanisms in PC pathogenesis can provide new insights for its treatment. In the present review, inflammation and related pathways as well as role of gut microbiome in the regulation of PC pathogenesis are highlighted. The various kinds of interleukins and chemokines are able to regulate angiogenesis, metastasis, proliferation, inflammation and therapy resistance in PC cells. Furthermore, a number of molecular pathways including NF-κB, TLRs and TGF-β demonstrate dysregulation in PC aggravating inflammation and tumorigenesis. Therapeutic regulation of these pathways can reverse inflammation and progression of PC. Both chronic and acute pancreatitis have been shown to be risk factors in the development of PC, further highlighting the role of inflammation. Finally, the composition of gut microbiota can be a risk factor for PC development through affecting pathways such as NF-κB to mediate inflammation.
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Affiliation(s)
- XiaoLiang Chen
- Department of General Surgery and Integrated Traditional Chinese and Western Medicine Oncology, Tiantai People'S Hospital of Zhejiang Province(Tiantai Branch of Zhejiang Provincial People'S Hospital), Hangzhou Medical College, Taizhou, Zhejiang, China
| | - Feixia Sun
- Nursing Department, Shandong First Medical University Affiliated Occupational Disease Hospital (Shandong Provincial Occupational Disease Hospital), Jinan, China
| | - Xuqin Wang
- Department of Oncology, Chongqing General Hospital, Chongqing University, Chongqing, 401120, China
| | - Xiaoqiang Feng
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong, China
| | - Amir Reza Aref
- VitroVision Department, DeepkinetiX, Inc, Boston, MA, USA
| | - Yu Tian
- Research Center, the Huizhou Central People'S Hospital, Guangdong Medical University, Huizhou, Guangdong, China.
- School of Public Health, Benedictine University, No. 5700 College Road, Lisle, IL, 60532, USA.
| | - Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, Shandong, China.
| | - Dengfeng Wu
- Department of Emergency, The People'S Hospital of Gaozhou, No. 89 Xiguan Road, Gaozhou, 525200, Guangdong, China.
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He R, Qi P, Shu L, Ding Y, Zeng P, Wen G, Xiong Y, Deng H. Dysbiosis and extraintestinal cancers. J Exp Clin Cancer Res 2025; 44:44. [PMID: 39915884 PMCID: PMC11804008 DOI: 10.1186/s13046-025-03313-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 01/31/2025] [Indexed: 02/09/2025] Open
Abstract
The gut microbiota plays a crucial role in safeguarding host health and driving the progression of intestinal diseases. Despite recent advances in the remarkable correlation between dysbiosis and extraintestinal cancers, the underlying mechanisms are yet to be fully elucidated. Pathogenic microbiota, along with their metabolites, can undermine the integrity of the gut barrier through inflammatory or metabolic pathways, leading to increased permeability and the translocation of pathogens. The dissemination of pathogens through the circulation may contribute to the establishment of an immune-suppressive environment that promotes carcinogenesis in extraintestinal organs either directly or indirectly. The oncogenic cascade always engages in the disruption of hormonal regulation and inflammatory responses, the induction of genomic instability and mutations, and the dysregulation of adult stem cell proliferation. This review aims to comprehensively summarize the existing evidence that points to the potential role of dysbiosis in the malignant transformation of extraintestinal organs such as the liver, breast, lung, and pancreas. Additionally, we delve into the limitations inherent in current methodologies, particularly the challenges associated with differentiating low loads gut-derived microbiome within tumors from potential sample contamination or symbiotic microorganisms. Although still controversial, an understanding of the contribution of translocated intestinal microbiota and their metabolites to the pathological continuum from chronic inflammation to tumors could offer a novel foundation for the development of targeted therapeutics.
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Affiliation(s)
- Ruishan He
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Pingqian Qi
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Linzhen Shu
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Yidan Ding
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Peng Zeng
- Department of Breast Surgery, Jiangxi Armed Police Corps Hospital, Nanchang, China
| | - Guosheng Wen
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Ying Xiong
- Department of General Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Huan Deng
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China.
- Tumor Immunology Institute, Nanchang University, Nanchang, 330006, Jiangxi, China.
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Vilà-Quintana L, Fort E, Pardo L, Albiol-Quer MT, Ortiz MR, Capdevila M, Feliu A, Bahí A, Llirós M, García-Velasco A, Morell Ginestà M, Laquente B, Pozas D, Moreno V, Garcia-Gil LJ, Duell EJ, Pimenoff VN, Carreras-Torres R, Aldeguer X. Metagenomic Study Reveals Phage-Bacterial Interactome Dynamics in Gut and Oral Microbiota in Pancreatic Diseases. Int J Mol Sci 2024; 25:10988. [PMID: 39456772 PMCID: PMC11507633 DOI: 10.3390/ijms252010988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/04/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Individuals with pancreatic-related health conditions usually show lower diversity and different composition of bacterial and viral species between the gut and oral microbiomes compared to healthy individuals. We performed a thorough microbiome analysis, using deep shotgun sequencing of stool and saliva samples obtained from patients with chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and healthy controls (HCs).We observed similar microbiota composition at the species level in both the gut and oral samples in PDAC patients compared to HCs, among which the most distinctive finding was that the abundance of oral-originated Fusobacterium nucleatum species did not differ between the oral and the gut samples. Moreover, comparing PDAC patients with HCs, Klebsiella oxytoca was significantly more abundant in the stool samples of PDAC patients, while Streptococcus spp. showed higher abundance in both the oral and stool samples of PDAC patients. Finally, the most important finding was the distinctive gut phage-bacterial interactome pattern among PDAC patients. CrAssphages, particularly Blohavirus, showed mutual exclusion with K. oxytoca species, while Burzaovirus showed co-occurrence with Enterobacteriaceae spp., which have been shown to be capable of inducing DNA damage in human pancreatic cells ex vivo. The interactome findings warrant further mechanistic studies, as our findings may provide new insights into developing microbiota-based diagnostic and therapeutic methods for pancreatic diseases.
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Affiliation(s)
- Laura Vilà-Quintana
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Esther Fort
- Department of Gastroenterology, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Laura Pardo
- Department of Gastroenterology, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Maria T. Albiol-Quer
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Maria Rosa Ortiz
- Department of Pathology, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Montserrat Capdevila
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Anna Feliu
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Anna Bahí
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Marc Llirós
- Bioinformatics and Bioimaging (BI-SQUARED) Research Group, Biosciences Department, Faculty of Sciences, Technology and Engineering, Universitat de Vic, 08500 Vic, Spain
| | - Adelaida García-Velasco
- Precision Oncology Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
- Institut Català d’Oncologia (ICO), Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Mireia Morell Ginestà
- Hereditary Cancer Program, Institut Català d’Oncologia (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), CIBERONC, 08908 Barcelona, Spain
| | - Berta Laquente
- Medical Oncology Department, Institut Català d’Oncologia (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
| | - Débora Pozas
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Victor Moreno
- Institut Català d’Oncologia (ICO), Institut de Recerca Biomedica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
- UBICS, University of Barcelona (UB), 08028 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 08036 Barcelona, Spain
| | - Librado Jesús Garcia-Gil
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Eric Jeffrey Duell
- Cancer Epidemiology Research Program, Unit of Nutrition and Cancer, Institut Català d’Oncologia (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
| | - Ville Nikolai Pimenoff
- Department of Clinical Science, Intervention and Technology—CLINTEC, Karolinska Institutet, 14152 Stockholm, Sweden
- Unit of Population Health, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
| | - Robert Carreras-Torres
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Xavier Aldeguer
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
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Zhu L, Chen G, Huang C, Gao H, Wang Y, Shen Y. SUMO3 inhibition by butyric acid suppresses cell viability and glycolysis and promotes gemcitabine antitumor activity in pancreatic cancer. Biol Direct 2024; 19:74. [PMID: 39183358 PMCID: PMC11345958 DOI: 10.1186/s13062-024-00513-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 08/08/2024] [Indexed: 08/27/2024] Open
Abstract
BACKGROUND Excavation of key molecules can help identify therapeutic targets and improve the prognosis of pancreatic cancer. This study evaluated the roles of SUMO3 in cell viability, glycolysis, gemcitabine (GEM) sensitivity, and the antitumor activity of butyric acid (BA) in pancreatic cancer. METHODS The mRNA and protein levels of SUMO3 were detected by qRT-PCR, Western blot, and immunohistochemical assay. SUMO3 was silenced or overexpressed in pancreatic cancer cells with or without Wnt/β-catenin pathway inhibitor, glycolysis inhibitor, GEM, or BA treatment. Cell viability was measured using the Cell Counting Kit-8 assay. Glycolysis was measured by determining the extracellular acidification rate, ATP level, and lactate content. Apoptosis was measured by flow cytometry, and TUNEL staining was used to examine in vitro and in vivo sensitivity to GEM chemotherapy. Luciferase reporter and chromatin immunoprecipitation assays were conducted to detect the binding of the SUMO3 promoter and NF-κB p65. RESULTS SUMO3 was increased and associated with poor survival in pancreatic cancer. SUMO3 knockdown decreased cell viability and glycolysis in vitro and inhibited tumor growth in vivo. SUMO3 overexpression increased cell viability and glycolysis in vitro through the β-catenin pathway. SUMO3 knockdown increased GEM sensitivity, whereas SUMO3 overexpression decreased GEM sensitivity and inhibited the antitumor activity of BA. BA promoted histone acetylation and p-IκBα expression to inhibit NF-κB p65-mediated SUMO3 transcription. CONCLUSION SUMO3 acted as an active molecule in cell survival and growth by enhancing glycolysis in response to either GEM or BA. The mechanism was related to the constitutive IκBα/NF-κB/SUMO3/β-catenin signaling pathway.
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Affiliation(s)
- Liming Zhu
- Minimally Invasive Therapy Center, Department of Integrative Oncology, Fudan University, Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Department of Oncology, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, 214071, China
| | - Gang Chen
- Department of Pediatric Cardiothoracic Surgery, Children's Hospital of Fudan University, Shanghai, 201102, China
| | - Changjing Huang
- Minimally Invasive Therapy Center, Department of Integrative Oncology, Fudan University, Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Huifeng Gao
- Minimally Invasive Therapy Center, Department of Integrative Oncology, Fudan University, Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yilin Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China.
| | - Yehua Shen
- Minimally Invasive Therapy Center, Department of Integrative Oncology, Fudan University, Shanghai Cancer Center, 270 Dong'An Road, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
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Grigorescu RR, Husar-Sburlan IA, Gheorghe C. Pancreatic Cancer: A Review of Risk Factors. Life (Basel) 2024; 14:980. [PMID: 39202722 PMCID: PMC11355429 DOI: 10.3390/life14080980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/28/2024] [Accepted: 08/01/2024] [Indexed: 09/03/2024] Open
Abstract
Pancreatic adenocarcinoma is one of the most lethal types of gastrointestinal cancer despite the latest medical advances. Its incidence has continuously increased in recent years in developed countries. The location of the pancreas can result in the initial symptoms of neoplasia being overlooked, which can lead to a delayed diagnosis and a subsequent reduction in the spectrum of available therapeutic options. The role of modifiable risk factors in pancreatic cancer has been extensively studied in recent years, with smoking and alcohol consumption identified as key contributors. However, the few screening programs that have been developed focus exclusively on genetic factors, without considering the potential impact of modifiable factors on disease occurrence. Thus, fully understanding and detecting the risk factors for pancreatic cancer represents an important step in the prevention and early diagnosis of this type of neoplasia. This review reports the available evidence on different risk factors and identifies the areas that could benefit the most from additional studies.
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Affiliation(s)
- Raluca Roxana Grigorescu
- Gastroenterology Department, “Sfanta Maria” Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | | | - Cristian Gheorghe
- Center for Digestive Disease and Liver Transplantation, Fundeni Clinical Institute, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Ke TM, Lophatananon A, Muir KR. Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization. Int J Mol Sci 2024; 25:4615. [PMID: 38731833 PMCID: PMC11082974 DOI: 10.3390/ijms25094615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 04/16/2024] [Accepted: 04/17/2024] [Indexed: 05/13/2024] Open
Abstract
This two-sample Mendelian randomization (MR) study was conducted to investigate the causal associations between type 2 diabetes mellitus (T2DM) and the risk of pancreatic cancer (PaCa), as this causal relationship remains inconclusive in existing MR studies. The selection of instrumental variables for T2DM was based on two genome-wide association study (GWAS) meta-analyses from European cohorts. Summary-level data for PaCa were extracted from the FinnGen and UK Biobank databases. Inverse variance weighted (IVW) and four other robust methods were employed in our MR analysis. Various sensitivity analyses and multivariable MR approaches were also performed to enhance the robustness of our findings. In the IVW and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analyses, the odds ratios (ORs) for each 1-unit increase in genetically predicted log odds of T2DM were approximately 1.13 for PaCa. The sensitivity tests and multivariable MR supported the causal link between T2DM and PaCa without pleiotropic effects. Therefore, our analyses suggest a causal relationship between T2DM and PaCa, shedding light on the potential pathophysiological mechanisms of T2DM's impact on PaCa. This finding underscores the importance of T2DM prevention as a strategy to reduce the risk of PaCa.
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Affiliation(s)
| | | | - Kenneth R. Muir
- Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, UK; (T.-M.K.); (A.L.)
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9
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Boicean A, Ichim C, Todor SB, Anderco P, Popa ML. The Importance of Microbiota and Fecal Microbiota Transplantation in Pancreatic Disorders. Diagnostics (Basel) 2024; 14:861. [PMID: 38732276 PMCID: PMC11082979 DOI: 10.3390/diagnostics14090861] [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: 04/02/2024] [Revised: 04/16/2024] [Accepted: 04/18/2024] [Indexed: 05/13/2024] Open
Abstract
The role of the intestinal microbiota in the diagnosis and treatment of pancreatic diseases is increasingly significant. Consequently, fecal microbiota transplantation (FMT) is emerging as a promising therapeutic avenue for various pancreatic disorders, including cancer, pancreatitis, and type 1 diabetes (T1D). This innovative procedure entails transferring gut microbiota from healthy donors to individuals affected by pancreatic ailments with the potential to restore intestinal balance and alleviate associated symptoms. FMT represents a pioneering approach to improve patient outcomes in pancreatic diseases, offering tailored treatments customized to individual microbiomes and specific conditions. Recent research highlights the therapeutic benefits of targeting the gut microbiota for personalized interventions in pancreatic disorders. However, a comprehensive understanding of the intricate interplay between gut microbiota and pancreatic physiology warrants further investigation. The necessity for additional studies and research endeavors remains crucial, especially in elucidating both adult and pediatric cases affected by pathological pancreatic conditions.
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Affiliation(s)
| | - Cristian Ichim
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania; (A.B.); (S.B.T.); (P.A.); (M.L.P.)
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Hunter C, Dia K, Boykins J, Perry K, Banerjee N, Cuffee J, Armstrong E, Morgan G, Banerjee HN, Banerjee A, Bhattacharya S. An investigation for phylogenetic characterization of human Pancreatic cancer microbiome by 16SrDNA Sequencing and Bioinformatics techniques. RESEARCH SQUARE 2024:rs.3.rs-4140368. [PMID: 38585738 PMCID: PMC10996791 DOI: 10.21203/rs.3.rs-4140368/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundance of microbiota in the pancreatic cancer.
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Affiliation(s)
- Colby Hunter
- Elizabeth City State University campus of The University of North Carolina
| | - Khadimou Dia
- Elizabeth City State University campus of The University of North Carolina
| | - Julia Boykins
- Elizabeth City State University campus of The University of North Carolina
| | - Karrington Perry
- Elizabeth City State University campus of The University of North Carolina
| | - Narendra Banerjee
- Elizabeth City State University campus of The University of North Carolina
| | - Jazmine Cuffee
- Elizabeth City State University campus of The University of North Carolina
| | - Erik Armstrong
- Elizabeth City State University campus of The University of North Carolina
| | - Gabrielle Morgan
- Elizabeth City State University campus of The University of North Carolina
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Jin D, Jin S, Zhou T, Cui Z, Guo B, Li G, Zhang C. Quantitative evaluation of gut microbiota composition in pancreatic cancer: A pooled study. Medicine (Baltimore) 2024; 103:e36907. [PMID: 38457538 PMCID: PMC10919531 DOI: 10.1097/md.0000000000036907] [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: 10/23/2023] [Revised: 12/15/2023] [Accepted: 12/18/2023] [Indexed: 03/10/2024] Open
Abstract
BACKGROUND Prior research has demonstrated a positive association between the composition of gut microbiota and the incidence of pancreatic cancer. Nevertheless, a thorough quantitative and systematic evaluation of the distinct properties of gut microbiota in individuals diagnosed with pancreatic cancer has yet to be conducted. The objective of this study is to examine alterations in the diversity of intestinal microbiota in individuals diagnosed with pancreatic cancer. METHODS Search for relevant literature published before July 2023 in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library, without any language restrictions. RESULTS A total of 12 studies were included, including 535 patients with pancreatic cancer and 677 healthy controls. Analysis was conducted on 6 phyla, 16 genera, and 6 species. The study found significant and distinctive changes in the α-diversity of gut microbiota, as well as in the relative abundance of multiple gut bacterial groups at the phylum, genus, and species levels in pancreatic cancer patients. CONCLUSION Overall, there are certain characteristic changes in the gut microbiota of pancreatic cancer patients. However, further research is warranted to elucidate the specific mechanism of action and the potential for treatment.
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Affiliation(s)
- Dachuan Jin
- Department of Clinical Laboratory, Sixth People’s Hospital of Zhengzhou, Zhengzhou, P.R. China
| | - Shunqin Jin
- Department of Radiology, Hebei Medical University, Shijiazhuang, P.R. China
| | - Tao Zhou
- Department of Geriatric Medicine, Key Laboratory of Cardiovascular Proteomics of Shandong University, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Zhongfeng Cui
- Department of Clinical Laboratory, Sixth People’s Hospital of Zhengzhou, Zhengzhou, P.R. China
| | - Baoqiang Guo
- Faculty of Science and Engineering, Department of Life Sciences, Manchester Metropolitan University, Manchester, U.K
| | - Guangming Li
- Department of Liver Disease, Sixth People’s Hospital of Zhengzhou, Zhengzhou, P.R. China
| | - Chunming Zhang
- Department of General Surgery, Sixth People’s Hospital of Zhengzhou, Zhengzhou, P.R. China
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Sbeit W, Gershovitz G, Shahin A, Shhadeh S, Salman M, Basheer M, Khoury T. Obesity Is Associated with Distal Migration of Pancreatic Adenocarcinoma to Body and Tail: A Multi-Center Study. Cancers (Basel) 2024; 16:359. [PMID: 38254848 PMCID: PMC10814908 DOI: 10.3390/cancers16020359] [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: 12/25/2023] [Revised: 01/09/2024] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
(1) Background: Pancreatic adenocarcinoma (PAC) is one of the most lethal types of cancer. Most cases of PAC occur in the head of the pancreas. Given the proximity of the pancreatic head to the bile duct, most patients present clinically during early stages of the disease, while distally located PAC could have delayed clinical presentation. (2) Aims: To assess predictors of non-head PAC. (3) Methods: A retrospective multicenter study was conducted, including all patients who had endoscopic ultrasound (EUS) for pancreatic masses and who had histologic confirmation of PAC. (4) Results: Of the 151 patients included, 92 (60.9%) had pancreatic head cancer, and 59 (39.1%) had distal pancreatic cancer. PAC at body was the most common location in the distal PAC group (31 patients (52.5%)). Logistic regression analysis demonstrated a significant association of obesity with distal migration of PAC (OR 4.44, 95% CI 1.15-17.19, p = 0.03), while none of the other assessed parameters showed a significant association. Notably, abdominal pain was more significantly associated with distal PAC vs. head location (OR 2.85, 95% CI 1.32-6.16, p = 0.008). (5) Conclusions: Obesity shows a significant association as a clinical predictor of distal PAC. Further studies are needed to better explore this association.
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Affiliation(s)
- Wisam Sbeit
- Gastroenterology Department, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (G.G.); (A.S.); (S.S.); (M.B.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Gil Gershovitz
- Gastroenterology Department, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (G.G.); (A.S.); (S.S.); (M.B.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Amir Shahin
- Gastroenterology Department, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (G.G.); (A.S.); (S.S.); (M.B.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Shhady Shhadeh
- Gastroenterology Department, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (G.G.); (A.S.); (S.S.); (M.B.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Mahmoud Salman
- Department of Surgery, Shaare Zedek Medical Center, Jerusalem 91120, Israel;
| | - Maamoun Basheer
- Gastroenterology Department, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (G.G.); (A.S.); (S.S.); (M.B.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Tawfik Khoury
- Gastroenterology Department, Galilee Medical Center, Nahariya 22100, Israel; (W.S.); (G.G.); (A.S.); (S.S.); (M.B.)
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
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13
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Marzhoseyni Z, Shaghaghi Z, Alvandi M, Shirvani M. Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer. Curr Cancer Drug Targets 2024; 24:612-628. [PMID: 38213140 DOI: 10.2174/0115680096274860231111210214] [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: 07/30/2023] [Revised: 09/09/2023] [Accepted: 09/25/2023] [Indexed: 01/13/2024]
Abstract
Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.
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Affiliation(s)
- Zeynab Marzhoseyni
- Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Iran, Sari, Iran
| | - Zahra Shaghaghi
- Cancer Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maryam Alvandi
- Cardiovascular Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Nuclear Medicine and Molecular Imaging, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Maria Shirvani
- Infectious Disease Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
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14
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Lyu Y, Xie F, Chen B, Shin WS, Chen W, He Y, Leung KT, Tse GMK, Yu J, To KF, Kang W. The nerve cells in gastrointestinal cancers: from molecular mechanisms to clinical intervention. Oncogene 2024; 43:77-91. [PMID: 38081962 PMCID: PMC10774121 DOI: 10.1038/s41388-023-02909-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/22/2023] [Accepted: 11/24/2023] [Indexed: 01/10/2024]
Abstract
Gastrointestinal (GI) cancer is a formidable malignancy with significant morbidity and mortality rates. Recent studies have shed light on the complex interplay between the nervous system and the GI system, influencing various aspects of GI tumorigenesis, such as the malignance of cancer cells, the conformation of tumor microenvironment (TME), and the resistance to chemotherapies. The discussion in this review first focused on exploring the intricate details of the biological function of the nervous system in the development of the GI tract and the progression of tumors within it. Meanwhile, the cancer cell-originated feedback regulation on the nervous system is revealed to play a crucial role in the growth and development of nerve cells within tumor tissues. This interaction is vital for understanding the complex relationship between the nervous system and GI oncogenesis. Additionally, the study identified various components within the TME that possess a significant influence on the occurrence and progression of GI cancer, including microbiota, immune cells, and fibroblasts. Moreover, we highlighted the transformation relationship between non-neuronal cells and neuronal cells during GI cancer progression, inspiring the development of strategies for nervous system-guided anti-tumor drugs. By further elucidating the deep mechanism of various neuroregulatory signals and neuronal intervention, we underlined the potential of these targeted drugs translating into effective therapies for GI cancer treatment. In summary, this review provides an overview of the mechanisms of neuromodulation and explores potential therapeutic opportunities, providing insights into the understanding and management of GI cancers.
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Affiliation(s)
- Yang Lyu
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- CUHK-Shenzhen Research Institute, Shenzhen, China
| | - Fuda Xie
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- CUHK-Shenzhen Research Institute, Shenzhen, China
| | - Bonan Chen
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- CUHK-Shenzhen Research Institute, Shenzhen, China
| | - Wing Sum Shin
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Wei Chen
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Yulong He
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Kam Tong Leung
- Department of Pediatrics, The Chinese University of Hong Kong, Hong Kong, China
| | - Gary M K Tse
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Ka Fai To
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Wei Kang
- Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
- Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China.
- CUHK-Shenzhen Research Institute, Shenzhen, China.
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15
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Fraile-Martinez O, García-Montero C, Pekarek L, Saz JV, Álvarez-Mon MÁ, Barrena-Blázquez S, García-Honduvilla N, Buján J, Asúnsolo Á, Coca S, Alvarez-Mon M, Guijarro LG, Saez MA, Ortega MA. Decreased survival in patients with pancreatic cancer may be associated with an increase in histopathological expression of inflammasome marker NLRP3. Histol Histopathol 2024; 39:35-40. [PMID: 37057822 DOI: 10.14670/hh-18-617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2023]
Abstract
Pancreatic cancer is a malignant neoplasm that, despite its low frequency, has a 5-year survival rate of less than 10%. The study of different histopathological markers has allowed a better understanding of the onset and development of this type of tumor as well as facilitating an approach to clinical variables based on their diagnostic, prognostic, and predictive value. In this sense, the NLRP3 protein of the inflammasome has been shown to be a component of great relevance in the initiation and progression of pancreatic cancer, although the value of this biomarker in patients has not yet been clarified. In this study, we selected 41 patients with pancreatic cancer and followed them for 60 months (5 years), evaluating their NLRP3 expression using immunohistochemical techniques. Furthermore, by performing Kaplan-Meier curves, we evaluated the survival of these patients in relation to their NLRP3 expression. Our results show that a significant percentage of our cohort had high expression of this component (90.74%) and that there is an inverse relationship between the expression of NLRP3 and patient survival. High levels of NLRP3 expression are related to lower survival and worse prognosis in these patients, possibly due to an ineffective immune system response and increased tumor-promoted inflammation. Future studies should be aimed at confirming these results in larger groups and evaluating various clinical strategies based on this knowledge.
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Affiliation(s)
- Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Leonel Pekarek
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Oncology Service, Guadalajara University Hospital, Guadalajara, Spain
| | - José V Saz
- Department of Biomedicine and Biotechnology, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain
| | - Miguel Ángel Álvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | | | - Natalio García-Honduvilla
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Julia Buján
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Ángel Asúnsolo
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Spain
| | - Santiago Coca
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine (CIBEREHD), University Hospital Príncipe de Asturias, Alcala de Henares, Spain
| | - Luis G Guijarro
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcalá, Alcala de Henares, Spain
| | - Miguel A Saez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, Alcala de Henares, Spain
| | - Miguel A Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), Madrid, Spain
- Cancer Registry and Pathology Department, Principe de Asturias University Hospital, Alcala de Henares, Spain.
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16
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Ramezani F, Pourghazi F, Eslami M, Gholami M, Mohammadian Khonsari N, Ejtahed HS, Larijani B, Qorbani M. Dietary fiber intake and all-cause and cause-specific mortality: An updated systematic review and meta-analysis of prospective cohort studies. Clin Nutr 2024; 43:65-83. [PMID: 38011755 DOI: 10.1016/j.clnu.2023.11.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 10/11/2023] [Accepted: 11/07/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Accumulating evidence supports the effects of dietary fiber on the risk of non-communicable diseases (NCDs). However, there is no updated systematic review and meta-analysis that compares and pools the effect of different types of fiber on mortality. METHODS In this systematic review and meta-analysis, all prospective cohort studies that evaluated the relationship between dietary fiber intake and all-cause or cause-specific mortality were included. The PubMed, SCOPUS, and Web of Science databases were searched up to October 2022. Data extraction and quality assessment were performed by two researchers independently. Heterogeneity between studies was assessed using Chi-square based test. Random/fixed effect meta-analysis was used to pool the hazard ratios (HR) or relative risks (RR) and 95 % confidence intervals (CI) for the association between different types of fiber and mortality. RESULTS This systematic review included 64 eligible studies, with a total sample size of 3512828 subjects, that investigated the association between dietary fiber intake and mortality from all-cause, cardiovascular disease (CVD), and cancer. Random-effect meta-analysis shows that higher consumption of total dietary fiber, significantly decreased the risk of all-cause mortality, CVD-related mortality, and cancer-related mortality by 23, 26 and 22 % (HR:0.77; 95%CI (0.73,0.82), HR:0.74; 95%CI (0.71,0.77) and HR:0.78; 95%CI (0.68,0.87)), respectively. The consumption of insoluble fiber tended to be more effective than soluble fiber intake in reducing the risk of total mortality and mortality due to CVD and cancer. Additionally, dietary fiber from whole grains, cereals, and vegetables was associated with a reduced risk of all-cause mortality, while dietary fiber from nuts and seeds reduced the risk of CVD-related death by 43 % (HR:0.57; 95 % CI (0.38,0.77)). CONCLUSION This comprehensive meta-analysis provides additional evidence supporting the protective association between fiber intake and all-cause and cause-specific mortality rates.
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Affiliation(s)
- Fatemeh Ramezani
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzad Pourghazi
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maysa Eslami
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Gholami
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Qorbani
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
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17
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Getsina M, Tsyba N, Polyakov P, Beloborodova N, Chernevskaya E. Blood Serum and Drainage Microbial and Mitochondrial Metabolites in Patients after Surgery for Pancreatic Cancer. Metabolites 2023; 13:1198. [PMID: 38132880 PMCID: PMC10744670 DOI: 10.3390/metabo13121198] [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: 11/24/2023] [Revised: 12/11/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023] Open
Abstract
Pancreatic cancer (PC) has the highest mortality rate of all major cancers in the world despite improvements in clinical care and an understanding of the biology of pancreatic cancer. A study of 64 patients with verified pancreatic cancer who underwent surgery was included. Sampling was carried out at three points: before surgery and on days 1-3 after surgery and 5-7 days after surgery. Drainage fluid collection was taken from the drains installed intraoperatively one day after surgery. Tyrosine and phenylalanine metabolites and two mitochondrial metabolites, namely succinic and fumaric acids, were identified and quantified by GC-MS in the serum of healthy donors and patients. Differences in the metabolomic profile were found between the patients and healthy people. A statistically significant decrease in the level of p-hydroxyphenyllactic acid (p-HPhLA), the amount of sum 3 sepsis-associated metabolites (Σ 3AMM), as well as fumaric and succinic acids in patients was observed. It was also noted that p-hydroxyphenyllactic acid in the preoperative period may be considered as a predictor of complications and longer postoperative recovery.
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Affiliation(s)
- Maria Getsina
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25-2 Petrovka Str., 107031 Moscow, Russia
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18
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He J, Li H, Jia J, Liu Y, Zhang N, Wang R, Qu W, Liu Y, Jia L. Mechanisms by which the intestinal microbiota affects gastrointestinal tumours and therapeutic effects. MOLECULAR BIOMEDICINE 2023; 4:45. [PMID: 38032415 PMCID: PMC10689341 DOI: 10.1186/s43556-023-00157-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 11/08/2023] [Indexed: 12/01/2023] Open
Abstract
The intestinal microbiota is considered to be a forgotten organ in human health and disease. It maintains intestinal homeostasis through various complex mechanisms. A significant body of research has demonstrated notable differences in the gut microbiota of patients with gastrointestinal tumours compared to healthy individuals. Furthermore, the dysregulation of gut microbiota, metabolites produced by gut bacteria, and related signal pathways can partially explain the mechanisms underlying the occurrence and development of gastrointestinal tumours. Therefore, this article summarizes the latest research progress on the gut microbiota and gastrointestinal tumours. Firstly, we provide an overview of the composition and function of the intestinal microbiota and discuss the mechanisms by which the intestinal flora directly or indirectly affects the occurrence and development of gastrointestinal tumours by regulating the immune system, producing bacterial toxins, secreting metabolites. Secondly, we present a detailed analysis of the differences of intestinal microbiota and its pathogenic mechanisms in colorectal cancer, gastric cancer, hepatocellular carcinoma, etc. Lastly, in terms of treatment strategies, we discuss the effects of the intestinal microbiota on the efficacy and toxic side effects of chemotherapy and immunotherapy and address the role of probiotics, prebiotics, FMT and antibiotic in the treatment of gastrointestinal tumours. In summary, this article provides a comprehensive review of the pathogenic mechanisms of and treatment strategies pertaining to the intestinal microbiota in patients with gastrointestinal tumours. And provide a more comprehensive and precise scientific basis for the development of microbiota-based treatments for gastrointestinal tumours and the prevention of such tumours.
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Affiliation(s)
- Jikai He
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Haijun Li
- Department of Gastrointestinal Surgery, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010017, Inner Mongolia, China
| | - Jiaqi Jia
- Graduate School of Youjiang Medical University for Nationalities, No. 98 Chengcheng Road, Youjiang District, Baise City, 533000, China
| | - Yang Liu
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Ning Zhang
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Rumeng Wang
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Wenhao Qu
- Graduate School of Youjiang Medical University for Nationalities, No. 98 Chengcheng Road, Youjiang District, Baise City, 533000, China
| | - Yanqi Liu
- Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot City, 010050, Inner Mongolia, China.
| | - Lizhou Jia
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China.
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19
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Jiang Z, Mou Y, Wang H, Li L, Jin T, Wang H, Liu M, Jin W. Causal effect between gut microbiota and pancreatic cancer: a two-sample Mendelian randomization study. BMC Cancer 2023; 23:1091. [PMID: 37950180 PMCID: PMC10636952 DOI: 10.1186/s12885-023-11493-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 10/08/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed. METHODS In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study. RESULTS At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403-0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157-3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128-3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072-1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071-1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran's Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC. CONCLUSIONS Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.
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Grants
- WKJ-ZJ-2201 Scientific research fund of national health commision of China, Key health science and technology program of Zhejiang Province
- WKJ-ZJ-2201 Scientific research fund of national health commision of China, Key health science and technology program of Zhejiang Province
- WKJ-ZJ-2201 Scientific research fund of national health commision of China, Key health science and technology program of Zhejiang Province
- WKJ-ZJ-2201 Scientific research fund of national health commision of China, Key health science and technology program of Zhejiang Province
- WKJ-ZJ-2201 Scientific research fund of national health commision of China, Key health science and technology program of Zhejiang Province
- 2022C03099 Key Project of social welfare program of Zhejiang Science and Technology Department,'Lingyan'Program
- 2022C03099 Key Project of social welfare program of Zhejiang Science and Technology Department,'Lingyan'Program
- 2022C03099 Key Project of social welfare program of Zhejiang Science and Technology Department,'Lingyan'Program
- 2022C03099 Key Project of social welfare program of Zhejiang Science and Technology Department,'Lingyan'Program
- 2022C03099 Key Project of social welfare program of Zhejiang Science and Technology Department,'Lingyan'Program
- Key Project of social welfare program of Zhejiang Science and Technology Department,’Lingyan’Program
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Affiliation(s)
- Zhichen Jiang
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Yiping Mou
- Department of General Surgery, Devision of Dastroenterology and Pancreas, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, Zhejiang, China
| | - Huiju Wang
- Department of General Surgery, Devision of Dastroenterology and Pancreas, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, Zhejiang, China
| | - Li Li
- Department of General Surgery, Devision of Dastroenterology and Pancreas, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, Zhejiang, China
| | - Tianyu Jin
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - He Wang
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Mingyang Liu
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Weiwei Jin
- Department of General Surgery, Devision of Dastroenterology and Pancreas, Affiliated People's Hospital, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
- Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, Zhejiang, China.
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20
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Hong W, Huang G, Wang D, Xu Y, Qiu J, Pei B, Qian D, Meng X. Gut microbiome causal impacts on the prognosis of breast cancer: a Mendelian randomization study. BMC Genomics 2023; 24:497. [PMID: 37644405 PMCID: PMC10464481 DOI: 10.1186/s12864-023-09608-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 08/20/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Growing evidence has shown that gut microbiome composition is associated with breast cancer (BC), but the causality remains unknown. We aimed to investigate the link between BC prognosis and the gut microbiome at various oestrogen receptor (ER) statuses. METHODS We performed a genome-wide association study (GWAS) to analyse the gut microbiome of BC patients, the dataset for which was collected by the Breast Cancer Association Consortium (BCAC). The analysis was executed mainly via inverse variance weighting (IVW); the Mendelian randomization (MR) results were verified by heterogeneity tests, sensitivity analysis, and pleiotropy analysis. RESULTS Our findings identified nine causal relationships between the gut microbiome and total BC cases, with ten and nine causal relationships between the gut microbiome and ER-negative (ER-) and ER-positive (ER+) BC, respectively. The family Ruminococcaceae and genus Parabacteroides were most apparent among the three categories. Moreover, the genus Desulfovibrio was expressed in ER- BC and total BC, whereas the genera Sellimonas, Adlercreutzia and Rikenellaceae appeared in the relationship between ER + BC and total BC. CONCLUSION Our MR inquiry confirmed that the gut microbiota is causally related to BC. This further explains the link between specific bacteria for prognosis of BC at different ER statuses. Considering that potential weak instrument bias impacts the findings and that the results are limited to European females due to data constraints, further validation is crucial.
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Affiliation(s)
- Weimin Hong
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, China
| | - Guoxin Huang
- Department of Evidence-Based Medicine Center, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China
| | - Danhong Wang
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, China
| | - Yadan Xu
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, China
| | - Jie Qiu
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, China
| | - Bin Pei
- Department of Evidence-Based Medicine Center, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China.
| | - Da Qian
- Department of Burn and Plastic Surgery-Hand Surgery, Changshu Hospital Affiliated to Soochow University Changshu No 1 People's Hospital, Changshu, 215500, China.
| | - Xuli Meng
- General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, China.
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21
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Papa V, Schepis T, Coppola G, Chiappetta MF, Del Vecchio LE, Rozera T, Quero G, Gasbarrini A, Alfieri S, Papa A. The Role of Microbiota in Pancreatic Cancer. Cancers (Basel) 2023; 15:3143. [PMID: 37370753 DOI: 10.3390/cancers15123143] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 06/02/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023] Open
Abstract
Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In addition, some bacterial strains can produce carcinogens that promote the growth of cancer cells. Research has also focused on pancreatic and oral microbiota. Changes in these microbiota can contribute to the development and progression of PC. Furthermore, patients with periodontal disease have an increased risk of developing PC. The potential use of microbiota as a prognostic marker or to predict patients' responses to chemotherapy or immunotherapy is also being explored. Overall, the role of microbiota-including the gut, pancreatic, and oral microbiota-in PC is an active research area. Understanding these associations could lead to new diagnostic and therapeutic targets for this deadly disease.
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Affiliation(s)
- Valerio Papa
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Tommaso Schepis
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Gaetano Coppola
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Michele Francesco Chiappetta
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Livio Enrico Del Vecchio
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Tommaso Rozera
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Giuseppe Quero
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Sergio Alfieri
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Digestive Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Alfredo Papa
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
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22
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Ruze R, Song J, Yin X, Chen Y, Xu R, Wang C, Zhao Y. Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review. Signal Transduct Target Ther 2023; 8:139. [PMID: 36964133 PMCID: PMC10039087 DOI: 10.1038/s41392-023-01376-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 01/31/2023] [Accepted: 02/15/2023] [Indexed: 03/26/2023] Open
Abstract
Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers. The growing interest in this area is prominently actuated by the increasing obesity and DM prevalence, which is partially responsible for the slight but constant increase in pancreatic cancer (PC) occurrence. PC is a highly lethal malignancy characterized by its insidious symptoms, delayed diagnosis, and devastating prognosis. The intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent whole-body systemic changes that are suitable for cancer initiation. The main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple pathways. Detrimental alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment (TME) for carcinogenesis, which can be exacerbated by several crucial pathophysiological processes and TME components, such as autophagy, endoplasmic reticulum stress, oxidative stress, epithelial-mesenchymal transition, and exosome secretion. This review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity- and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.
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Affiliation(s)
- Rexiati Ruze
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Jianlu Song
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Xinpeng Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Yuan Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Ruiyuan Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Chengcheng Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China.
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China.
- Key Laboratory of Research in Pancreatic Tumors, Chinese Academy of Medical Sciences, 100023, Beijing, China.
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23
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Zhong H, Liu S, Zhu J, Wu L. Associations between genetically predicted levels of blood metabolites and pancreatic cancer risk. Int J Cancer 2023; 153:103-110. [PMID: 36757187 DOI: 10.1002/ijc.34466] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 01/14/2023] [Accepted: 01/30/2023] [Indexed: 02/10/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies, which is featured by systematic metabolism. Thus, a better understanding of metabolic dysregulation in PDAC is important to better characterize its etiology. Here, we performed a large metabolome-wide association study (MWAS) to systematically explore associations between genetically predicted metabolite levels in blood and PDAC risk. Using data from 881 subjects of European descent in the TwinsUK Project, comprehensive genetic models were built to predict serum metabolite levels. These prediction models were applied to the genetic data of 8275 cases and 6723 controls included in the PanScan (I, II and III) and PanC4 consortia. After assessing the metabolite-PDAC risk associations by a slightly modified TWAS/FUSION framework, we identified five metabolites (including two dipeptides) showing significant associations with PDAC risk at false discovery rate (FDR) <0.05. Integrated with gut microbial information, two-sample Mendelian randomization (MR) analyses were further performed to investigate the relationship among serum metabolites, gut microbiome features and PDAC. The flavonoid-degrading bacteria Flavonifractor sp90199495 was found to be associated with metabolite X-21849 and it was also shown to be associated with PDAC risk. Collectively, our study identified novel candidate metabolites for PDAC risk, which could lead to new insights into the etiology of PDAC and improved treatment options.
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Affiliation(s)
- Hua Zhong
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Shuai Liu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Jingjing Zhu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA
| | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA
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24
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Jiang Z, Zhang W, Zhang Z, Sha G, Wang D, Tang D. Intratumoral microbiota: A new force in diagnosing and treating pancreatic cancer. Cancer Lett 2023; 554:216031. [PMID: 36481214 DOI: 10.1016/j.canlet.2022.216031] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/17/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022]
Abstract
Pancreatic cancer is an increasingly growing source of cancer-related deaths and is often diagnosed at advanced stages. Its treatment is difficult because of the poor results of conventional treatments, such as surgery, chemotherapy, and radiotherapy. Microbiota and their products can regulate the microenvironment of pancreatic tumors, the biological behavior of pancreatic cancer cells, and the functionality of the immune system. Promising results have been achieved in treating pancreatic cancer by regulating microbiota. However, intratumoral microbiota is still in its infancy as a new field of discovery for pancreatic cancer. This review summarizes the mechanisms by which intratumoral microbiota causes pancreatic cancer tumorigenesis, progression, and metastasis and demonstrates their significant potential in diagnosing and treating pancreatic cancer. Additionally, we present an outlook on the future of intratumoral microbiota in treating pancreatic cancer.
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Affiliation(s)
- Zhengting Jiang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China.
| | - Wenjie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China.
| | - Zhilin Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China.
| | - Gengyu Sha
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, 225001, China.
| | - Daorong Wang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
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25
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Zhao J, Yang Y, Xu H, Zheng J, Shen C, Chen T, Wang T, Wang B, Yi J, Zhao D, Wu E, Qin Q, Xia L, Qiao L. Data-independent acquisition boosts quantitative metaproteomics for deep characterization of gut microbiota. NPJ Biofilms Microbiomes 2023; 9:4. [PMID: 36693863 PMCID: PMC9873935 DOI: 10.1038/s41522-023-00373-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 01/11/2023] [Indexed: 01/26/2023] Open
Abstract
Metaproteomics can provide valuable insights into the functions of human gut microbiota (GM), but is challenging due to the extreme complexity and heterogeneity of GM. Data-independent acquisition (DIA) mass spectrometry (MS) has been an emerging quantitative technique in conventional proteomics, but is still at the early stage of development in the field of metaproteomics. Herein, we applied library-free DIA (directDIA)-based metaproteomics and compared the directDIA with other MS-based quantification techniques for metaproteomics on simulated microbial communities and feces samples spiked with bacteria with known ratios, demonstrating the superior performance of directDIA by a comprehensive consideration of proteome coverage in identification as well as accuracy and precision in quantification. We characterized human GM in two cohorts of clinical fecal samples of pancreatic cancer (PC) and mild cognitive impairment (MCI). About 70,000 microbial proteins were quantified in each cohort and annotated to profile the taxonomic and functional characteristics of GM in different diseases. Our work demonstrated the utility of directDIA in quantitative metaproteomics for investigating intestinal microbiota and its related disease pathogenesis.
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Affiliation(s)
- Jinzhi Zhao
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China
| | - Yi Yang
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China
- ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, 311200, Hangzhou, China
| | - Hua Xu
- Department of Core Facility of Basic Medical Sciences, and Department of Psychiatry of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China
| | - Jianxujie Zheng
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China
| | - Chengpin Shen
- Shanghai Omicsolution Co., Ltd, 201100, Shanghai, China
| | - Tian Chen
- Changhai Hospital, The Naval Military Medical University, 200433, Shanghai, China
| | - Tao Wang
- Department of Core Facility of Basic Medical Sciences, and Department of Psychiatry of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China
| | - Bing Wang
- College of Food Science and Technology, Shanghai Ocean University, 201306, Shanghai, China
| | - Jia Yi
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China
| | - Dan Zhao
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China
| | - Enhui Wu
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China
| | - Qin Qin
- Changhai Hospital, The Naval Military Medical University, 200433, Shanghai, China.
| | - Li Xia
- Department of Core Facility of Basic Medical Sciences, and Department of Psychiatry of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China.
| | - Liang Qiao
- Department of Chemistry, Shanghai Stomatological Hospital, Fudan University, 200000, Shanghai, China.
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26
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Binda C, Gibiino G, Sbrancia M, Coluccio C, Cazzato M, Carloni L, Cucchetti A, Ercolani G, Sambri V, Fabbri C. Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy. Cancers (Basel) 2022; 15:cancers15010001. [PMID: 36611999 PMCID: PMC9817971 DOI: 10.3390/cancers15010001] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/28/2022] [Accepted: 12/13/2022] [Indexed: 12/29/2022] Open
Abstract
Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis.
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Affiliation(s)
- Cecilia Binda
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Giulia Gibiino
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
- Correspondence: ; Tel.: +39-3488609557
| | - Monica Sbrancia
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Chiara Coluccio
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Maria Cazzato
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Lorenzo Carloni
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì, Italy
| | - Vittorio Sambri
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- Microbiology Unit, Hub Laboratory, AUSL della Romagna, 47121 Cesena, Italy
| | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
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27
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Gut Microbiota, the Potential Biological Medicine for Prevention, Intervention and Drug Sensitization to Fight Diseases. Nutrients 2022; 14:nu14204220. [PMID: 36296908 PMCID: PMC9610464 DOI: 10.3390/nu14204220] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 11/17/2022] Open
Abstract
As the largest “immune organ” of human beings, the gut microbiota is symbiotic and mutually beneficial with the human host, playing multiple physiological functions. Studies have long shown that dysbiosis of gut microbiota is associated with almost all human diseases, mainly including type II diabetes, cancers, neurodegenerative diseases, autism spectrum disorder, and kidney diseases. As a novel and potential biological medicine for disease prevention, intervention and drug sensitization, the gut microbiota has attracted more and more attention recently. Although the gut microbiota is a comprehensive microbial community, several star bacteria have emerged as possible tools to fight against various diseases. This review aims to elucidate the relevance of gut microbiota dysbiosis with disease occurrence and progression, and mainly summarizes four well-known genera with therapeutic and sensitizing potential, Akkermansia, Bifidobacterium, Lactobacillus and Parabacteroides, thoroughly elucidate their potential value as biological drugs to treat diverse disease.
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Unlocking the Potential of the Human Microbiome for Identifying Disease Diagnostic Biomarkers. Diagnostics (Basel) 2022; 12:diagnostics12071742. [PMID: 35885645 PMCID: PMC9315466 DOI: 10.3390/diagnostics12071742] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 07/10/2022] [Accepted: 07/14/2022] [Indexed: 02/07/2023] Open
Abstract
The human microbiome encodes more than three million genes, outnumbering human genes by more than 100 times, while microbial cells in the human microbiota outnumber human cells by 10 times. Thus, the human microbiota and related microbiome constitute a vast source for identifying disease biomarkers and therapeutic drug targets. Herein, we review the evidence backing the exploitation of the human microbiome for identifying diagnostic biomarkers for human disease. We describe the importance of the human microbiome in health and disease and detail the use of the human microbiome and microbiota metabolites as potential diagnostic biomarkers for multiple diseases, including cancer, as well as inflammatory, neurological, and metabolic diseases. Thus, the human microbiota has enormous potential to pave the road for a new era in biomarker research for diagnostic and therapeutic purposes. The scientific community needs to collaborate to overcome current challenges in microbiome research concerning the lack of standardization of research methods and the lack of understanding of causal relationships between microbiota and human disease.
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Roles of Microbiota in Cancer: From Tumor Development to Treatment. JOURNAL OF ONCOLOGY 2022; 2022:3845104. [PMID: 35342407 PMCID: PMC8941494 DOI: 10.1155/2022/3845104] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/24/2022] [Accepted: 03/01/2022] [Indexed: 12/11/2022]
Abstract
Cancer as a second leading cause of death arises from multifactorial pathology. The association of microbiota and their products with various pathologic conditions including cancer is receiving significant attention over the past few years. Mounting evidence showed that human microbiota is an emerging target in tumor onset, progression, prevention, and even diagnosis. Accordingly, modulating this composition might influence the response to tumor therapy and therapeutic resistance as well. Through this review, one could conceive of complex interaction between the microbiome and cancer in either positive or negative manner by which may hold potential for finding novel preventive and therapeutic strategies against cancer.
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Mekadim C, Skalnikova HK, Cizkova J, Cizkova V, Palanova A, Horak V, Mrazek J. Dysbiosis of skin microbiome and gut microbiome in melanoma progression. BMC Microbiol 2022; 22:63. [PMID: 35216552 PMCID: PMC8881828 DOI: 10.1186/s12866-022-02458-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/29/2022] [Indexed: 12/11/2022] Open
Abstract
Background The microbiome alterations are associated with cancer growth and may influence the immune system and response to therapy. Particularly, the gut microbiome has been recently shown to modulate response to melanoma immunotherapy. However, the role of the skin microbiome has not been well explored in the skin tumour microenvironment and the link between the gut microbiome and skin microbiome has not been investigated in melanoma progression. Therefore, the aim of the present study was to examine associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression. Results Parallel analysis of cutaneous microbiota and faecal microbiota of the same individuals was performed in 8 to 12 weeks old MeLiM piglets. The bacterial composition of samples was analysed by high throughput sequencing of the V4-V5 region of the 16S rRNA gene. A significant difference in microbiome diversity and richness between melanoma tissue and healthy skin and between the faecal microbiome of MeLiM piglets and control piglets were observed. Both Principal Coordinate Analysis and Non-metric multidimensional scaling revealed dissimilarities between different bacterial communities. Linear discriminant analysis effect size at the genus level determined different potential biomarkers in multiple bacterial communities. Lactobacillus, Clostridium sensu stricto 1 and Corynebacterium 1 were the most discriminately higher genera in the healthy skin microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus and Bacteroides were discriminately abundant in melanoma tissue microbiome. Bacteroides, Fusobacterium and Escherichia-Shigella were associated with the faecal microbiota of MeLiM piglets. Potential functional pathways analysis based on the KEGG database indicated significant differences in the predicted profile metabolisms between the healthy skin microbiome and melanoma tissue microbiome. The faecal microbiome of MeLiM piglets was enriched by genes related to membrane transports pathways allowing for the increase of intestinal permeability and alteration of the intestinal mucosal barrier. Conclusion The associations between melanoma progression and dysbiosis in the skin microbiome as well as dysbiosis in the gut microbiome were identified. Results provide promising information for further studies on the local skin and gut microbiome involvement in melanoma progression and may support the development of new therapeutic approaches. Supplementary Information The online version contains supplementary material available at 10.1186/s12866-022-02458-5.
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Affiliation(s)
- Chahrazed Mekadim
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czech Republic
| | - Helena Kupcova Skalnikova
- Laboratory of Applied Proteome Analyses, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 277 21, Libechov, Czech Republic
| | - Jana Cizkova
- Laboratory of Applied Proteome Analyses, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 277 21, Libechov, Czech Republic.,Department of Radiobiology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic
| | - Veronika Cizkova
- Laboratory of Applied Proteome Analyses, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 277 21, Libechov, Czech Republic.,Department of Cell Biology, Faculty of Science, Charles University, Vinicna 7, 128 00, Prague, Czech Republic
| | - Anna Palanova
- Laboratory of Applied Proteome Analyses, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 277 21, Libechov, Czech Republic
| | - Vratislav Horak
- Laboratory of Applied Proteome Analyses, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Rumburska 89, 277 21, Libechov, Czech Republic
| | - Jakub Mrazek
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20, Prague, Czech Republic.
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Huang Y, Zhu N, Zheng X, Liu Y, Lu H, Yin X, Hao H, Tan Y, Wang D, Hu H, Liang Y, Li X, Hu Z, Yin Y. Intratumor Microbiome Analysis Identifies Positive Association Between Megasphaera and Survival of Chinese Patients With Pancreatic Ductal Adenocarcinomas. Front Immunol 2022; 13:785422. [PMID: 35145519 PMCID: PMC8821101 DOI: 10.3389/fimmu.2022.785422] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 01/03/2022] [Indexed: 12/24/2022] Open
Abstract
Human tumors harbor a plethora of microbiota. It has been shown that the composition and diversity of intratumor microbiome are significantly associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC). However, the association in Chinese patients as well as the effect of different microorganisms on inhibiting tumor growth are unclear. In this study, we collected tumor samples resected from long-term and short-term PDAC survivors and performed 16S rRNA amplicon sequencing. We found that the microbiome in samples with different survival time were significantly different, and the differential bacterial composition was associated with the metabolic pathways in the tumor microenvironment. Furthermore, administration of Megasphaera, one of the differential bacteria, induced a better tumor growth inhibition effect when combined with the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1) treatment in mice bearing 4T1 tumor. These results indicate that specific intratumor microbiome can enhance the anti-tumor effect in the host, laying a foundation for further clarifying the underlying detailed mechanism.
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Affiliation(s)
- Yu Huang
- Department of General Surgery, No.903 Hospital of People’s Liberation Army Joint Logistic Support Forcel, Hangzhou, China
| | - Ning Zhu
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Xing Zheng
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Yanhong Liu
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Haopeng Lu
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Xiaochen Yin
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Huaijie Hao
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Yan Tan
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Dongjie Wang
- Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Han Hu
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Yong Liang
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
| | - Xinxing Li
- Department of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Zhiqian Hu
- Department of General Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, China
| | - Yiming Yin
- Department of Research and Development, Shenzhen Xbiome Biotech Co. Ltd., Shenzhen, China
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Li M, Wang X, Wang Y, Bao S, Chang Q, Liu L, Zhang S, Sun L. Strategies for Remodeling the Tumor Microenvironment Using Active Ingredients of Ginseng-A Promising Approach for Cancer Therapy. Front Pharmacol 2022; 12:797634. [PMID: 35002732 PMCID: PMC8727883 DOI: 10.3389/fphar.2021.797634] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/06/2021] [Indexed: 12/21/2022] Open
Abstract
The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.
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Affiliation(s)
- Mo Li
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China.,Department of Thyroid Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Xin Wang
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ying Wang
- Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shunchao Bao
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Qing Chang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Linlin Liu
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Shuai Zhang
- Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China
| | - Liwei Sun
- Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
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Mahapatra S, Mohanty S, Mishra R, Prasad P. An overview of cancer and the human microbiome. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 191:83-139. [DOI: 10.1016/bs.pmbts.2022.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Schepis T, De Lucia SS, Nista EC, Manilla V, Pignataro G, Ojetti V, Piccioni A, Gasbarrini A, Franceschi F, Candelli M. Microbiota in Pancreatic Diseases: A Review of the Literature. J Clin Med 2021; 10:5920. [PMID: 34945216 PMCID: PMC8704740 DOI: 10.3390/jcm10245920] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 02/05/2023] Open
Abstract
The gut microbiota is a critical element in the balance between human health and disease. Its impairment, defined as dysbiosis, is associated with gastroenterological and systemic diseases. Pancreatic secretions are involved in the composition and changes of the gut microbiota, and the gut microbiota may colonize the pancreatic parenchyma and be associated with the occurrence of diseases. The gut microbiota and the pancreas influence each other, resulting in a "gut microbiota-pancreas axis". Moreover, the gut microbiota may be involved in pancreatic diseases, both through direct bacterial colonization and an indirect effect of small molecules and toxins derived from dysbiosis. Pancreatic diseases such as acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer are common gastroenterological diseases associated with high morbidity and mortality. The involvement of the microbiota in pancreatic diseases is increasingly recognized. Therefore, modifying the intestinal bacterial flora could have important therapeutic implications on these pathologies. The aim of this study is to review the literature to evaluate the alterations of the gut microbiota in pancreatic diseases, and the role of the microbiota in the treatment of these diseases.
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Affiliation(s)
- Tommaso Schepis
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (T.S.); (S.S.D.L.); (E.C.N.); (V.M.); (A.G.)
| | - Sara S. De Lucia
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (T.S.); (S.S.D.L.); (E.C.N.); (V.M.); (A.G.)
| | - Enrico C. Nista
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (T.S.); (S.S.D.L.); (E.C.N.); (V.M.); (A.G.)
| | - Vittoria Manilla
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (T.S.); (S.S.D.L.); (E.C.N.); (V.M.); (A.G.)
| | - Giulia Pignataro
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (G.P.); (V.O.); (A.P.); (F.F.)
| | - Veronica Ojetti
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (G.P.); (V.O.); (A.P.); (F.F.)
| | - Andrea Piccioni
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (G.P.); (V.O.); (A.P.); (F.F.)
| | - Antonio Gasbarrini
- Medical and Surgical Science Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (T.S.); (S.S.D.L.); (E.C.N.); (V.M.); (A.G.)
| | - Francesco Franceschi
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (G.P.); (V.O.); (A.P.); (F.F.)
| | - Marcello Candelli
- Emergency Medicine Department, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Università Cattolica del Sacro Cuore di Roma, 00168 Roma, Italy; (G.P.); (V.O.); (A.P.); (F.F.)
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Nucci D, Santangelo OE, Provenzano S, Fatigoni C, Nardi M, Ferrara P, Gianfredi V. Dietary Fiber Intake and Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis of Observational Studies. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182111556. [PMID: 34770068 PMCID: PMC8583332 DOI: 10.3390/ijerph182111556] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/21/2021] [Accepted: 10/30/2021] [Indexed: 12/24/2022]
Abstract
The burden of pancreatic cancer varies greatly across countries, with the number of deaths, incident cases, and disability-adjusted life years more than doubling in recent years, and with high-income countries having the highest incidence and mortality rates. We conducted this systematic review with meta-analysis with the goal of summarizing the current evidence on dietary fiber intake and its role in reducing the risk of pancreatic cancer, given the importance of identifying risk factors. This systematic review followed the guidelines of the Cochrane Collaboration and the Meta-analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The structured literature search was conducted on PubMed/Medline and Scopus, combining free text words and medical subject headings. Our review contained 18 records at the end of the process. Our results show that dietary fiber intake reduces the risk of pancreatic cancer. When the analysis was differentiated according to the type of fiber considered, sub-grouped by gender (reduction of around 60% among women), and when case-control studies were conducted, the strength of the association increased. Clinicians and policymakers should improve interventions to raise the population's awareness regarding the consumption of high-fiber diets, both in practice and in terms of public health policy.
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Affiliation(s)
- Daniele Nucci
- Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy; (D.N.); (M.N.)
| | | | | | - Cristina Fatigoni
- Department of Pharmaceutical Sciences, University of Perugia, 06122 Perugia, Italy;
| | - Mariateresa Nardi
- Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy; (D.N.); (M.N.)
| | - Pietro Ferrara
- Center for Public Health Research, University of Milan—Bicocca, 20900 Monza, Italy
- Value-Based Healthcare Unit, IRCCS MultiMedica, 20099 Sesto San Giovanni, Italy
- Correspondence:
| | - Vincenza Gianfredi
- School of Medicine, University Vita-Salute San Raffaele, 20132 Milan, Italy;
- CAPHRI Care and Public Health Research Institute, Maastricht University, 6211 Maastricht, The Netherlands
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Tonini V, Zanni M. Pancreatic cancer in 2021: What you need to know to win. World J Gastroenterol 2021; 27:5851-5889. [PMID: 34629806 PMCID: PMC8475010 DOI: 10.3748/wjg.v27.i35.5851] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 07/14/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the solid tumors with the worst prognosis. Five-year survival rate is less than 10%. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients. Moreover, surgery is still associated with high post-operative morbidity, while other therapies still offer very disappointing results. This article reviews every aspect of pancreatic cancer, focusing on the elements that can improve prognosis. It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.
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Affiliation(s)
- Valeria Tonini
- Department of Medical Sciences and Surgery, University of Bologna- Emergency Surgery Unit, IRCCS Sant’Orsola Hospital, Bologna 40121, Italy
| | - Manuel Zanni
- University of Bologna, Emergency Surgery Unit, IRCCS Sant'Orsola Hospital, Bologna 40121, Italy
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Brandi G, Turroni S, McAllister F, Frega G. The Human Microbiomes in Pancreatic Cancer: Towards Evidence-Based Manipulation Strategies? Int J Mol Sci 2021; 22:9914. [PMID: 34576078 PMCID: PMC8471697 DOI: 10.3390/ijms22189914] [Citation(s) in RCA: 12] [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: 07/28/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 02/07/2023] Open
Abstract
Recent pieces of evidence have emerged on the relevance of microorganisms in modulating responses to anticancer treatments and reshaping the tumor-immune microenvironment. On the one hand, many studies have addressed the role of the gut microbiota, providing interesting correlative findings with respect to etiopathogenesis and treatment responses. On the other hand, intra-tumoral bacteria are being recognized as intrinsic and essential components of the cancer microenvironment, able to promote a plethora of tumor-related aspects from cancer growth to resistance to chemotherapy. These elements will be probably more and more valuable in the coming years in early diagnosis and risk stratification. Furthermore, microbial-targeted intervention strategies may be used as adjuvants to current therapies to improve therapeutic responses and overall survival. This review focuses on new insights and therapeutic approaches that are dawning against pancreatic cancer: a neoplasm that arises in a central metabolic "hub" interfaced between the gut and the host.
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Affiliation(s)
- Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy;
| | - Florencia McAllister
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Giorgio Frega
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
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Sayed IM, Ramadan HKA, El-Mokhtar MA, Abdel-Wahid L. Microbiome and gastrointestinal malignancies. CURRENT OPINION IN PHYSIOLOGY 2021. [DOI: 10.1016/j.cophys.2021.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Abdul Rahman R, Lamarca A, Hubner RA, Valle JW, McNamara MG. The Microbiome as a Potential Target for Therapeutic Manipulation in Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13153779. [PMID: 34359684 PMCID: PMC8345056 DOI: 10.3390/cancers13153779] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/19/2021] [Accepted: 07/22/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Pancreatic cancer is one of the most lethal cancers. It is a difficult cancer to treat, and the complexity surrounding the pancreatic tumour is one of the contributing factors. The microbiome is the collection of microorganisms within an environment and its genetic material. They reside on body surfaces and most abundantly within the human gut in symbiotic balance with their human host. Disturbance in the balance can lead to many diseases, including cancers. Significant advances have been made in cancer treatment since the introduction of immunotherapy, and the microbiome may play a part in the outcome and survival of patients with cancer, especially those treated with immunotherapy. Immunotherapy use in pancreatic cancer remains challenging. This review will focus on the potential interaction of the microbiome with pancreas cancer and how this could be manipulated. Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.
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Affiliation(s)
- Rozana Abdul Rahman
- Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; (A.L.); (R.A.H.)
| | - Richard A. Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK; (A.L.); (R.A.H.)
| | - Juan W. Valle
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Mairéad G. McNamara
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
- Correspondence:
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Hu JX, Zhao CF, Chen WB, Liu QC, Li QW, Lin YY, Gao F. Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol 2021; 27:4298-4321. [PMID: 34366606 PMCID: PMC8316912 DOI: 10.3748/wjg.v27.i27.4298] [Citation(s) in RCA: 303] [Impact Index Per Article: 75.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/18/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low 5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.
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Affiliation(s)
- Jian-Xiong Hu
- Intensive Care Unit (ICU), Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China
| | - Cheng-Fei Zhao
- School of Pharmacy and Medical Technology, Putian University, Putian 351100, Fujian Province, China
- Key Laboratory of Pharmaceutical Analysis and Laboratory Medicine in University of Fujian Province, Putian University, Putian 351100, Fujian Province, China
| | - Wen-Biao Chen
- Department of Basic Medicine, Quanzhou Medical College, Quanzhou 362011, Fujian Province, China
| | - Qi-Cai Liu
- Department of Reproductive Medicine Centre, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Qu-Wen Li
- Department of Priority Laboratory for Zoonoses Research, Fujian Center for Disease Control and Prevention, Fuzhou 350001, Fujian Province, China
| | - Yan-Ya Lin
- Intensive Care Unit (ICU), Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China
| | - Feng Gao
- Department of Pathology, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Ma T, Chen Y, Li LJ, Zhang LS. Opportunities and Challenges for Gut Microbiota in Acute Leukemia. Front Oncol 2021; 11:692951. [PMID: 34307157 PMCID: PMC8293295 DOI: 10.3389/fonc.2021.692951] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 06/23/2021] [Indexed: 12/12/2022] Open
Abstract
Acute leukemia (AL) is a highly heterogeneous hematologic malignancy, and although great progress has been made in the treatment of AL with allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and new targeted drugs, problems such as infection and GVHD in AL treatment are still serious. How to reduce the incidence of AL, improve its prognosis and reduce the side effects of treatment is a crucial issue. The gut microbiota plays an important role in regulating disease progression, pathogen colonization, and immune responses. This article reviews recent advances in the gut microbiota and AL pathogenesis, infection, treatment and its role in allo-HSCT.
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Affiliation(s)
- Tao Ma
- Department of Hematology, Lanzhou University Second Hospital, Lanzhou, China.,Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yan Chen
- Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Li-Juan Li
- Department of Hematology, Lanzhou University Second Hospital, Lanzhou, China
| | - Lian-Sheng Zhang
- Department of Hematology, Lanzhou University Second Hospital, Lanzhou, China
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Veziant J, Villéger R, Barnich N, Bonnet M. Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer. Cancers (Basel) 2021; 13:2215. [PMID: 34063108 PMCID: PMC8124679 DOI: 10.3390/cancers13092215] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/29/2021] [Accepted: 05/01/2021] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota is crucial for physiological development and immunological homeostasis. Alterations of this microbial community called dysbiosis, have been associated with cancers such colorectal cancers (CRC). The pro-carcinogenic potential of this dysbiotic microbiota has been demonstrated in the colon. Recently the role of the microbiota in the efficacy of anti-tumor therapeutic strategies has been described in digestive cancers and in other cancers (e.g., melanoma and sarcoma). Different bacterial species seem to be implicated in these mechanisms: F. nucleatum, B. fragilis, and colibactin-associated E. coli (CoPEC). CoPEC bacteria are prevalent in the colonic mucosa of patients with CRC and they promote colorectal carcinogenesis in susceptible mouse models of CRC. In this review, we report preclinical and clinical data that suggest that CoPEC could be a new factor predictive of poor outcomes that could be used to improve cancer management. Moreover, we describe the possibility of using these bacteria as new therapeutic targets.
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Affiliation(s)
- Julie Veziant
- Microbes Intestin Inflammation et Susceptibilité de l’Hôte (M2iSH) UMR 1071 Inserm/Université Clermont Auvergne, USC-INRAE 2018, CRNH Auvergne, 63000 Clermont-Ferrand, France; (J.V.); (R.V.); (N.B.)
- Department of Digestive, Hepatobiliary and Endocrine Surgery Paris Descartes University Cochin Hospital, 75000 Paris, France
| | - Romain Villéger
- Microbes Intestin Inflammation et Susceptibilité de l’Hôte (M2iSH) UMR 1071 Inserm/Université Clermont Auvergne, USC-INRAE 2018, CRNH Auvergne, 63000 Clermont-Ferrand, France; (J.V.); (R.V.); (N.B.)
- Laboratoire Ecologie & Biologie des Interactions, UMR CNRS 7267 Université de Poitiers, 86000 Poitiers, France
| | - Nicolas Barnich
- Microbes Intestin Inflammation et Susceptibilité de l’Hôte (M2iSH) UMR 1071 Inserm/Université Clermont Auvergne, USC-INRAE 2018, CRNH Auvergne, 63000 Clermont-Ferrand, France; (J.V.); (R.V.); (N.B.)
| | - Mathilde Bonnet
- Microbes Intestin Inflammation et Susceptibilité de l’Hôte (M2iSH) UMR 1071 Inserm/Université Clermont Auvergne, USC-INRAE 2018, CRNH Auvergne, 63000 Clermont-Ferrand, France; (J.V.); (R.V.); (N.B.)
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Abstract
ABSTRACT Microorganisms can help maintain homeostasis in humans by providing nutrition, maintaining hormone balance, and regulating inflammatory responses. In the case of imbalances, these microbes can cause various diseases, even malignancy. Pancreatic cancer (PC) is characterized by high tumor invasiveness, distant metastasis, and insensitivity to traditional chemotherapeutic drugs, and it is confirmed that PC is closely related to microorganisms. Recently, most studies based on clinical samples or case reports discussed the positive or negative relationships between microorganisms and PC. However, the specific mechanisms are blurry, especially the involved immunological pathways, and the roles of beneficial flora have usually been ignored. We reviewed studies published through September 2020 as identified using PubMed, MEDLINE, and Web of Science. We mainly introduced the traits of oral, gastrointestinal, and intratumoral microbes in PC and summarized the roles of these microbes in tumorigenesis and tumoral development through immunological pathways, in addition to illustrating the relationships between metabolic diseases with PC by microorganism. In addition, we identified microorganisms as biomarkers for early diagnosis and immunotherapy. This review will be significant for greater understanding the effect of microorganisms in PC and provide more meaningful guidance for future clinical applications.
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Affiliation(s)
- Xin Wei
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
| | - Chunlei Mei
- Institute of Reproductive Health, Huazhong University of Science and Technology, Wuhan, China
| | - Xixi Li
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
| | - Yingjun Xie
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
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