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Oh VKS, Li RW. Wise Roles and Future Visionary Endeavors of Current Emperor: Advancing Dynamic Methods for Longitudinal Microbiome Meta-Omics Data in Personalized and Precision Medicine. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2400458. [PMID: 39535493 DOI: 10.1002/advs.202400458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 09/16/2024] [Indexed: 11/16/2024]
Abstract
Understanding the etiological complexity of diseases requires identifying biomarkers longitudinally associated with specific phenotypes. Advanced sequencing tools generate dynamic microbiome data, providing insights into microbial community functions and their impact on health. This review aims to explore the current roles and future visionary endeavors of dynamic methods for integrating longitudinal microbiome multi-omics data in personalized and precision medicine. This work seeks to synthesize existing research, propose best practices, and highlight innovative techniques. The development and application of advanced dynamic methods, including the unified analytical frameworks and deep learning tools in artificial intelligence, are critically examined. Aggregating data on microbes, metabolites, genes, and other entities offers profound insights into the interactions among microorganisms, host physiology, and external stimuli. Despite progress, the absence of gold standards for validating analytical protocols and data resources of various longitudinal multi-omics studies remains a significant challenge. The interdependence of workflow steps critically affects overall outcomes. This work provides a comprehensive roadmap for best practices, addressing current challenges with advanced dynamic methods. The review underscores the biological effects of clinical, experimental, and analytical protocol settings on outcomes. Establishing consensus on dynamic microbiome inter-studies and advancing reliable analytical protocols are pivotal for the future of personalized and precision medicine.
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Affiliation(s)
- Vera-Khlara S Oh
- Big Biomedical Data Integration and Statistical Analysis (DIANA) Research Center, Department of Data Science, College of Natural Sciences, Jeju National University, Jeju City, Jeju Do, 63243, South Korea
| | - Robert W Li
- United States Department of Agriculture, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD, 20705, USA
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Dadgar-Zankbar L, Elahi Z, Shariati A, Khaledi A, Razavi S, Khoshbayan A. Exploring the role of Fusobacterium nucleatum in colorectal cancer: implications for tumor proliferation and chemoresistance. Cell Commun Signal 2024; 22:547. [PMID: 39548531 PMCID: PMC11566256 DOI: 10.1186/s12964-024-01909-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 10/24/2024] [Indexed: 11/18/2024] Open
Abstract
Fusobacterium nucleatum (Fn) has been extensively studied for its connection to colorectal cancer (CRC) and its potential role in chemotherapy resistance. Studies indicate that Fn is commonly found in CRC tissues and is associated with unfavorable prognosis and treatment failure. It has been shown that Fn promotes chemoresistance by affecting autophagy, a cellular process that helps cells survive under stressful conditions. Additionally, Fn targets specific signaling pathways that activate particular microRNAs and modulate the response to chemotherapy. Understanding the current molecular mechanisms and investigating the importance of Fn-inducing chemoresistance could provide valuable insights for developing novel therapies. This review surveys the role of Fn in tumor proliferation, metastasis, and chemoresistance in CRC, focusing on its effects on the tumor microenvironment, gene expression, and resistance to conventional chemotherapy drugs. It also discusses the therapeutic implications of targeting Fn in CRC treatment and highlights the need for further research.
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Affiliation(s)
- Leila Dadgar-Zankbar
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Elahi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Vice Chancellery of Education and Research, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
| | - Aref Shariati
- Infectious Diseases Research Center (IDRC), Arak University of Medical Sciences, Arak, Iran
| | - Azad Khaledi
- Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
- Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, P.O. Box: 87155.111, Kashan, 87154, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Amin Khoshbayan
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
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3
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Mignini I, Piccirilli G, Galasso L, Termite F, Esposto G, Ainora ME, Gasbarrini A, Zocco MA. From the Colon to the Liver: How Gut Microbiota May Influence Colorectal Cancer Metastatic Potential. J Clin Med 2024; 13:420. [PMID: 38256554 PMCID: PMC10815973 DOI: 10.3390/jcm13020420] [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: 12/18/2023] [Revised: 01/08/2024] [Accepted: 01/11/2024] [Indexed: 01/24/2024] Open
Abstract
The gut microbiota's influence on human tumorigenesis is a burning topic in medical research. With the new ontological perspective, which considers the human body and its pathophysiological processes as the result of the interaction between its own eukaryotic cells and prokaryotic microorganisms living in different body niches, great interest has arisen in the role of the gut microbiota on carcinogenesis. Indeed, dysbiosis is currently recognized as a cancer-promoting condition, and multiple molecular mechanisms have been described by which the gut microbiota may drive tumor development, especially colorectal cancer (CRC). Metastatic power is undoubtedly one of the most fearsome features of neoplastic tissues. Therefore, understanding the underlying mechanisms is of utmost importance to improve patients' prognosis. The liver is the most frequent target of CRC metastasis, and new evidence reveals that the gut microbiota may yield an effect on CRC diffusion to the liver, thus defining an intriguing new facet of the so-called "gut-liver axis". In this review, we aim to summarize the most recent data about the microbiota's role in promoting or preventing hepatic metastasis from CRC, highlighting some potential future therapeutic targets.
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Affiliation(s)
| | | | | | | | | | | | | | - Maria Assunta Zocco
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (I.M.); (G.P.); (L.G.); (F.T.); (G.E.); (M.E.A.); (A.G.)
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Din SRU, Saeed S, Khan SU, Arbi FM, Xuefang G, Zhong M. Bacteria-driven cancer therapy: Exploring advancements and challenges. Crit Rev Oncol Hematol 2023; 191:104141. [PMID: 37742883 DOI: 10.1016/j.critrevonc.2023.104141] [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: 08/08/2023] [Revised: 09/15/2023] [Accepted: 09/18/2023] [Indexed: 09/26/2023] Open
Abstract
Cancer, a serious fatal disease caused by the uncontrolled growth of cells, is the biggest challenge flagging around medicine and health fields. Conventionally, various treatments-based strategies such as radiotherapy, chemotherapy, and alternative cancer therapies possess drugs that cannot reach the cancerous tissues and make them toxic to noncancerous cells. Cancer immunotherapy has made outstanding achievements in reducing the chances of cancer. Our considerable attention towards cancer-directed immune responses and the mechanisms behind which immune cells kill cancer cells have progressively been helpful in the advancement of new therapies. Among them, bacteria-based cancer immunotherapy has achieved much more attention due to smart and robust mechanisms in activating the host anti-tumor response. Moreover, bacterial-based therapy can be utilized as a single monotherapy or in combination with multiple anticancer immunotherapies to accelerate productive clinical results. Herein, we comprehensively reviewed recent advancements, challenges, and future perspectives in developing bacterial-based cancer immunotherapies.
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Affiliation(s)
- Syed Riaz Ud Din
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
| | - Sumbul Saeed
- School of Environment and Science, Griffith University, Nathan, QLD 4111, Australia
| | - Shahid Ullah Khan
- Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, College of Agronomy and Biotechnology, Southwest University, Beibei, Chongqing 400715, China; Engineering Research Center of South Upland Agriculture, Ministry of Education, Chongqing 400715, China; Women Medical and Dental College, Khyber Medical University, Peshawar, KPK 22020, Pakistan
| | - Fawad Mueen Arbi
- Quaid-e-Azam Medical College, Bahawalpur, Punjab 63100, Pakistan
| | - Guo Xuefang
- Department of Medical Microbiology, Dalian Medical University, Dalian 116044, China
| | - Mintao Zhong
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
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Senchukova MA. Genetic heterogeneity of colorectal cancer and the microbiome. World J Gastrointest Oncol 2023; 15:443-463. [PMID: 37009315 PMCID: PMC10052667 DOI: 10.4251/wjgo.v15.i3.443] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/06/2023] [Accepted: 02/22/2023] [Indexed: 03/14/2023] Open
Abstract
In 2020, the International Agency for Research on Cancer and the World Health Organization's GLOBOCAN database ranked colorectal cancer (CRC) as the third most common cancer in the world. Most cases of CRC (> 95%) are sporadic and develop from colorectal polyps that can progress to intramucosal carcinoma and CRC. Increasing evidence is accumulating that the gut microbiota can play a key role in the initiation and progression of CRC, as well as in the treatment of CRC, acting as an important metabolic and immunological regulator. Factors that may determine the microbiota role in CRC carcinogenesis include inflammation, changes in intestinal stem cell function, impact of bacterial metabolites on gut mucosa, accumulation of genetic mutations and other factors. In this review, I discuss the major mechanisms of the development of sporadic CRC, provide detailed characteristics of the bacteria that are most often associated with CRC, and analyze the role of the microbiome and microbial metabolites in inflammation initiation, activation of proliferative activity in intestinal epithelial and stem cells, and the development of genetic and epigenetic changes in CRC. I consider long-term studies in this direction to be very important, as they open up new opportunities for the treatment and prevention of CRC.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
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Yusuf K, Sampath V, Umar S. Bacterial Infections and Cancer: Exploring This Association And Its Implications for Cancer Patients. Int J Mol Sci 2023; 24:3110. [PMID: 36834525 PMCID: PMC9958598 DOI: 10.3390/ijms24043110] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 01/31/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Bacterial infections are common in the etiology of human diseases owing to the ubiquity of bacteria. Such infections promote the development of periodontal disease, bacterial pneumonia, typhoid, acute gastroenteritis, and diarrhea in susceptible hosts. These diseases may be resolved using antibiotics/antimicrobial therapy in some hosts. However, other hosts may be unable to eliminate the bacteria, allowing them to persist for long durations and significantly increasing the carrier's risk of developing cancer over time. Indeed, infectious pathogens are modifiable cancer risk factors, and through this comprehensive review, we highlight the complex relationship between bacterial infections and the development of several cancer types. For this review, searches were performed on the PubMed, Embase, and Web of Science databases encompassing the entirety of 2022. Based on our investigation, we found several critical associations, of which some are causative: Porphyromonas gingivalis and Fusobacterium nucleatum are associated with periodontal disease, Salmonella spp., Clostridium perfringens, Escherichia coli, Campylobacter spp., and Shigella are associated with gastroenteritis. Helicobacter pylori infection is implicated in the etiology of gastric cancer, and persistent Chlamydia infections present a risk factor for the development of cervical carcinoma, especially in patients with the human papillomavirus (HPV) coinfection. Salmonella typhi infections are linked with gallbladder cancer, and Chlamydia pneumoniae infection is implicated in lung cancer, etc. This knowledge helps identify the adaptation strategies used by bacteria to evade antibiotic/antimicrobial therapy. The article also sheds light on the role of antibiotics in cancer treatment, the consequences of their use, and strategies for limiting antibiotic resistance. Finally, the dual role of bacteria in cancer development as well as in cancer therapy is briefly discussed, as this is an area that may help to facilitate the development of novel microbe-based therapeutics as a means of securing improved outcomes.
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Affiliation(s)
- Kafayat Yusuf
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160, USA
- Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Venkatesh Sampath
- Department of Pediatrics and Gastroenterology, Children’s Mercy Hospital, Kansas City, KS 66160, USA
| | - Shahid Umar
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160, USA
- Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
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Irajizad E, Wu R, Vykoukal J, Murage E, Spencer R, Dennison JB, Moulder S, Ravenberg E, Lim B, Litton J, Tripathym D, Valero V, Damodaran S, Rauch GM, Adrada B, Candelaria R, White JB, Brewster A, Arun B, Long JP, Do KA, Hanash S, Fahrmann JF. Application of Artificial Intelligence to Plasma Metabolomics Profiles to Predict Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer. Front Artif Intell 2022; 5:876100. [PMID: 36034598 PMCID: PMC9403735 DOI: 10.3389/frai.2022.876100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied artificial intelligence to comprehensive metabolic profiles to identify additional metabolites associated with treatment response. Using a deep learning model (DLM), a metabolite panel consisting of two polyamines as well as nine additional metabolites was developed for improved prediction of RCB-II/III. The DLM has potential clinical value for identifying TNBC patients who are unlikely to respond to NACT and who may benefit from other treatment modalities.
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Affiliation(s)
- Ehsan Irajizad
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Ranran Wu
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jody Vykoukal
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Eunice Murage
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Rachelle Spencer
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jennifer B. Dennison
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Stacy Moulder
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Elizabeth Ravenberg
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Bora Lim
- Breast Cancer Research Program, Baylor College of Medicine, Houston, TX, United States
| | - Jennifer Litton
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Debu Tripathym
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Vicente Valero
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Senthil Damodaran
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Gaiane M. Rauch
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Beatriz Adrada
- Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Rosalind Candelaria
- Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jason B. White
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Abenaa Brewster
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Banu Arun
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - James P. Long
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Kim Anh Do
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Sam Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- *Correspondence: Sam Hanash
| | - Johannes F. Fahrmann
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Johannes F. Fahrmann
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Molecular Mechanisms of Cancer Drug Resistance: Emerging Biomarkers and Promising Targets to Overcome Tumor Progression. Cancers (Basel) 2022; 14:cancers14071614. [PMID: 35406386 PMCID: PMC8997078 DOI: 10.3390/cancers14071614] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 03/18/2022] [Indexed: 11/17/2022] Open
Abstract
Cancer still represents a major global burden, being the second leading cause of death worldwide [...].
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Oh VKS, Li RW. Large-Scale Meta-Longitudinal Microbiome Data with a Known Batch Factor. Genes (Basel) 2022; 13:392. [PMID: 35327945 PMCID: PMC8953633 DOI: 10.3390/genes13030392] [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: 12/25/2021] [Revised: 02/05/2022] [Accepted: 02/18/2022] [Indexed: 12/04/2022] Open
Abstract
Data contamination in meta-approaches where multiple biological samples are combined considerably affects the results of subsequent downstream analyses, such as differential abundance tests comparing multiple groups at a fixed time point. Little has been thoroughly investigated regarding the impact of the lurking variable of various batch sources, such as different days or different laboratories, in more complicated time series experimental designs, for instance, repeatedly measured longitudinal data and metadata. We highlight that the influence of batch factors is significant on subsequent downstream analyses, including longitudinal differential abundance tests, by performing a case study of microbiome time course data with two treatment groups and a simulation study of mimic microbiome longitudinal counts.
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Affiliation(s)
- Vera-Khlara S. Oh
- United States Department of Agriculture, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705, USA
- Department of Data Science, College of Natural Sciences, Jeju National University, Jeju City 690-756, Korea
| | - Robert W. Li
- United States Department of Agriculture, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705, USA
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