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Al-Beltagi M. Human milk oligosaccharide secretion dynamics during breastfeeding and its antimicrobial role: A systematic review. World J Clin Pediatr 2025; 14:104797. [PMID: 40491725 PMCID: PMC11947870 DOI: 10.5409/wjcp.v14.i2.104797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 02/19/2025] [Accepted: 02/27/2025] [Indexed: 03/18/2025] Open
Abstract
BACKGROUND Human milk oligosaccharides (HMOs) are bioactive components of breast milk with diverse health benefits, including shaping the gut microbiota, modulating the immune system, and protecting against infections. HMOs exhibit dynamic secretion patterns during lactation, influenced by maternal genetics and environmental factors. Their direct and indirect antimicrobial properties have garnered significant research interest. However, a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored. AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial, viral, and protozoal pathogens. METHODS A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library focused on studies investigating natural and synthetic HMOs, their secretion dynamics, and antimicrobial properties. Studies involving human, animal, and in vitro models were included. Data on HMO composition, temporal secretion patterns, and mechanisms of antimicrobial action were extracted. Quality assessment was performed using validated tools appropriate for study design. RESULTS A total of 44 studies were included, encompassing human, animal, and in vitro research. HMOs exhibited dynamic secretion patterns, with 2'-fucosyllactose (2'-FL) and lacto-N-tetraose peaking in early lactation and declining over time, while 3-fucosyllactose (3-FL) increased during later stages. HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition, biofilm disruption, and enzymatic activity impairment. Synthetic HMOs, including bioengineered 2'-FL and 3-FL, were structurally and functionally comparable to natural HMOs, effectively inhibiting pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Campylobacter jejuni. Additionally, HMOs exhibited synergistic effects with antibiotics, enhancing their efficacy against resistant pathogens. CONCLUSION HMOs are vital in antimicrobial defense, supporting infant health by targeting various pathogens. Both natural and synthetic HMOs hold significant potential for therapeutic applications, particularly in infant nutrition and as adjuncts to antibiotics. Further research, including clinical trials, is essential to address gaps in knowledge, validate findings, and explore the broader applicability of HMOs in improving maternal and neonatal health.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
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Bangolo A, Amoozgar B, Habibi M, Simms E, Nagesh VK, Wadhwani S, Wadhwani N, Auda A, Elias D, Mansour C, Abbott R, Jebara N, Zhang L, Gill S, Ahmed K, Ip A, Goy A, Cho C. Exploring the gut microbiome’s influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies. World J Gastrointest Pharmacol Ther 2025; 16:105375. [DOI: 10.4292/wjgpt.v16.i2.105375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 06/03/2025] Open
Abstract
BACKGROUND Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients’ survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending on its composition, and functional integrity. Dysbiosis, characterized by disruption in the gut microbial ecosystem, is very common in cancer patients. This microbial imbalance is implicated in anemia causation through diminished iron absorption, persistent low-grade inflammation, and suppression of erythropoiesis.
AIM To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies. It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia, identifies unique challenges associated with various cancer types, and evaluates the efficacy of microbiome-focused therapies. Through this integrative approach, the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.
METHODS A literature search was performed using multiple databases, including Google Scholar, PubMed, Scopus, and Web of Science, using a combination of keywords and Boolean operators to refine results. Keywords included “cancer-associated anemia”, “gut microbiome”, “intestinal microbiota”, “iron metabolism”, “gut dysbiosis”, “short-chain fatty acids”, “hematopoiesis”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. Articles published in English between 2000 and December 2024 were included, with a focus on contemporary and relevant findings.
RESULTS Therapeutic strategies aimed at restoration of gut microbial homeostasis, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), can inhibit anemia-causing pathways by enhancing microbial diversity, suppressing detrimental flora, reducing systemic inflammation and optimizing nutrient absorption.
CONCLUSION Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients. Microbiome-centered interventions, such as probiotics, prebiotics, dietary modifications, and FMT, have shown efficacy in restoring microbial balance, reducing inflammation, and enhancing nutrient bioavailability. Emerging approaches, including engineered probiotics and bacteriophage therapies, are promising precision-based, customizable solutions for various microbiome compositions and imbalances. Future research should focus on integrating microbiome-targeted strategies with established anemia therapies.
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Affiliation(s)
- Ayrton Bangolo
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Behzad Amoozgar
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Maryam Habibi
- Department of Research, Tulane National Primate Research Center, Covington, LA 70433, United States
| | - Elizabeth Simms
- Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States
| | - Vignesh K Nagesh
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Shruti Wadhwani
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Nikita Wadhwani
- Department of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Auda Auda
- Department of Family Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Daniel Elias
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Charlene Mansour
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Robert Abbott
- Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nisrene Jebara
- Columbia University School of Nursing, New York, NY 10032, United States
| | - Lili Zhang
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Sarvarinder Gill
- Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Kareem Ahmed
- Department of Medicine, University of Washington, Seattle, WA 98195, United States
| | - Andrew Ip
- Division of Lymphoma, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Andre Goy
- Division of Lymphoma, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Christina Cho
- Division of Stem Cell Transplant and Cellular Therapy, John Theurer Cancer Center, Hackensack, NJ 07601, United States
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3
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Zhao Y, Shen K, Lu Q, Huang W, Kang X, Xie L. Alterations of metabolites related to microbiota-gut-brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients. Open Life Sci 2025; 20:20251115. [PMID: 40443546 PMCID: PMC12120410 DOI: 10.1515/biol-2025-1115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/08/2025] [Accepted: 04/16/2025] [Indexed: 06/02/2025] Open
Abstract
Co-occurring symptoms such as depression, anxiety, fatigue, and sleep disorders are frequently comorbid with cancer. The causes of these cancer-related symptom clusters are hypothesized sharing a common biological mechanism. This study explored pattern differences of some gut metabolites (glucocorticoids, short-chain fatty acids, gut microbial metabolites from tryptophan) in plasma samples from patients with four types of cancer. Metabolomics analysis was performed to indicate the differences of metabolites. Discrimination model and diagnostic model were constructed using orthogonal partial least squares discriminant analysis, and differential metabolites were screened, then receiver-operating characteristic curve analysis was performed to evaluate the performance of these models. Melatonin (MLT), indole propionic, and skatole were screened as the common differential metabolites shared by four types of cancer, indicating that the intestinal microbial metabolic pathway of tryptophan plays a key role in the occurrence and development of malignant tumors. The area under the curve values for the potential candidate biomarker predictors in univariate analysis ranged from 0.771 to 0.989, and in multivariate analysis ranged from 0.985 to 1.00. The sensitivity and specificity of the multivariable model were 94.7-100 and 96.4-100%, respectively. These biomarkers also had good performance in discriminating different pairs of cancer. The analysis of gut microbiota metabolites allows us to characterize the common metabolic characteristics of patients with various cancers. The intestinal microbial metabolic pathway of tryptophan plays a key role in the occurrence and development of malignant tumors.
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Affiliation(s)
- Yuqin Zhao
- Gynecology Department, Jiangsu Province Hospital of Chinese Medicine,
Nanjing, Jiangsu, 210029, China
| | - Kangwei Shen
- Key Laboratory of Child Development and Learning Science (Ministry of Education), School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, PR China
| | - Qing Lu
- Key Laboratory of Child Development and Learning Science (Ministry of Education), School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, PR China
| | - Wei Huang
- Department of Radiotherapy, Jiangsu Province Hospital of Chinese Medicine,
Nanjing, Jiangsu, 210029, China
| | - Xuejun Kang
- Key Laboratory of Child Development and Learning Science (Ministry of Education), School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, PR China
| | - Li Xie
- College of Animal Science and Technology, Jinling Institute of Technology,
Nanjing, 210038, PR China
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Alowo D, Olum S, Mukisa IM, Ongeng D. Prebiotic potential of oligosaccharides extracted from improved Ugandan varieties of millet, sesame, soybean, and sorghum: enhancing probiotic growth and enteric pathogen inhibition. BMC Microbiol 2025; 25:307. [PMID: 40389861 PMCID: PMC12087199 DOI: 10.1186/s12866-025-04028-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 05/07/2025] [Indexed: 05/21/2025] Open
Abstract
Functional gastrointestinal disorders like diarrhea continue to affect children under five years in low-income countries. Incorporating health-enhancing bioactive compounds such as prebiotics in diet offers a promising solution. This study investigated prebiotic potential of oligosaccharides extracted from improved varieties of millet (Seremi 2, Naromil 2), sesame (Sesim 2, Sesim 3), soybean (Maksoy 3N, Maksoy 6N), and sorghum (Narosorg 2, Narosorg 4), commonly consumed in Uganda. These were compared to their respective indigenous variety. This study employed standardized methods for optical density measurement, culture preparation, and oligosaccharide extraction to evaluate prebiotic properties. We investigated whether plant-based oligosaccharides could enhance the effectiveness of probiotics, specifically Lactiplantibacillus plantarum (ATCC 14917) and Lacticaseibacillus rhamnosus (ATCC 7469), in antagonizing common enteric pathogens (Salmonella enterica subsp. enterica (ATCC 13076) and Shigella flexneri (ATCC 12022)). Approximately 4-8 log CFU/ml of each probiotic was incubated in 2% w/v oligosaccharide extracts at 37 °C to evaluate the influence of the extracts on their growth, short-chain fatty acid (SCFA) production and antagonistic activity. Maximum cell density, which exceeded the minimum recommended probiotic cell density (6 log CFU/ml), was achieved during 24-h incubation period. The probiotics exhibited optimal growth in extracts of Sesim 2, Maksoy 3N, Narosorg 2 and indigenous millet variety resulting in a 68-84% increase in cell densities. The concentration of SCFA concentration was significantly higher (p < 0.05) in soybean-based oligosaccharides. Both probiotics antagonized growth of Salmonella and Shigella by more than 40% when cultured on Sesim 2, Maksoy 3N, Narosorg 2 and indigenous millet variety, while maintaining the probiotic cell densities above the minimum recommended level. These varieties show great potential as functional ingredients for developing synbiotic-rich foods to promote gut and public health. However, to evaluate the oligosaccharides prebiotic efficacy, in vitro fermentation using fecal microbiota and in vivo studies are necessary to determine gut microbiota changes and interactions.
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Affiliation(s)
- Docus Alowo
- Department of Food Science and Postharvest Technology, Faculty of Agriculture and Environment, Gulu University, P.O. Box, 166, Gulu, Uganda.
- Department of Food Innovation and Nutrition, Faculty of Agriculture and Environmental Sciences, Mountains of the Moon University, P.O. Box, 837, Fort Portal, Uganda.
| | - Solomon Olum
- Department of Food Science and Postharvest Technology, Faculty of Agriculture and Environment, Gulu University, P.O. Box, 166, Gulu, Uganda
| | - Ivan Muzira Mukisa
- Department of Food Technology & Nutrition, School of Food Technology, Nutrition & Bioengineering, College of Agricultural and Environmental Sciences, Makerere University, P.O. Box 7062, Kampala, Uganda
| | - Duncan Ongeng
- Department of Food Science and Postharvest Technology, Faculty of Agriculture and Environment, Gulu University, P.O. Box, 166, Gulu, Uganda
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Deng M, Li X, Wu H, Xue D, Wang Y, Guo R, Cui Y, Jin C, Luo F, Li H. The current status and prospects of gut microbiota combined with PD-1/PD-L1 inhibitors in the treatment of colorectal cancer: a review. BMC Gastroenterol 2025; 25:380. [PMID: 40380157 PMCID: PMC12083025 DOI: 10.1186/s12876-025-03968-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 05/02/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common malignant tumor. Immune checkpoint inhibitors (ICIs), particularly those targeting programmed cell death protein 1(PD-1) and programmed cell death ligand 1(PD-L1), have shown promising potential in the treatment of CRC. Specific gut microbiota can modulate the efficacy of ICIs through immune or metabolic pathways. This review summarizes recent advances in the combined application of gut microbiota and PD-1/PD-L1 inhibitors in the treatment of CRC, aiming to provide insights for expanding clinical treatment options for CRC. MATERIALS AND METHODS We employed a systematic search strategy to screen relevant literature from databases such as PubMed, EMBASE, Medline, Cochrane Library, and Clinical Trial registries, with the search period covering from the inception of each database to October 2024. This study includes animal models and human trial subjects. Data extraction and literature screening were strictly carried out by two independent researchers. RESULTS A total of 8 animal studies and 5 clinical trials were included to evaluate the effects of gut microbiota combined with PD-1/PD-L1 inhibitors in CRC. Tumor types included Microsatellite Stability(MSS), Microsatellite Instability-Low(MSI-L), and MSI-H CRC. Main outcomes were tumor volume, weight, and incidence; one study reported survival. Study durations ranged from 20 days to 26 weeks. Two studies used human fecal microbiota transplantation(FMT), and six applied experimental microbial interventions. The 5 clinical trials used ORR as the primary endpoint.Some also reported DCR, PFS, and OS. Two studies targeted Microsatellite Instability-High(MSI-H)/Deficient Mismatch Repair(dMMR), two MSS/Proficient Mismatch Repair(pMMR), and one lacked molecular subtype specification. All trials used full microbiota transplantation; one has released preliminary data. CONCLUSION The treatment regimen combining gut microbiota with PD-1/PD-L1 inhibitors has shown promising therapeutic prospects in both animal studies and clinical research, although most clinical trials are data remain limited. Future studies should focus on: (1) gene-edited probiotic strains with targeted modifications; (2) the synergistic effects of multiple probiotics; and (3) conducting high-quality, multicenter clinical trials.
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Affiliation(s)
- Min Deng
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Xiaoyu Li
- Department of Tumor Biobank, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Huiming Wu
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
| | - Dingwen Xue
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Yize Wang
- Department of General Surgery, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Renkai Guo
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Yipeng Cui
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Chenfei Jin
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Fei Luo
- Department of Breast Surgery, Affliated Cancer Hospital of Shanxi Medical University, Shanxi Provincial Cancer Hospital, Taiyuan, China.
| | - Huiyu Li
- Department of General Surgery, Third Hospital of Shanxi Medical University , Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
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Mafe AN, Büsselberg D. The Effect of Microbiome-Derived Metabolites in Inflammation-Related Cancer Prevention and Treatment. Biomolecules 2025; 15:688. [PMID: 40427581 PMCID: PMC12109317 DOI: 10.3390/biom15050688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 04/29/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
Chronic inflammation plays a crucial role in cancer development, yet the mechanisms linking the microbiome to inflammation-related carcinogenesis remain unclear. Emerging evidence suggests that microbiome-derived metabolites influence inflammatory pathways, presenting both challenges and opportunities for therapy. However, a deeper understanding of how these metabolites regulate inflammation and contribute to cancer prevention is still needed. This review explores recent advances in microbiome-derived metabolites and their roles in inflammation-related carcinogenesis. It highlights key molecular mechanisms, emerging therapies, and unresolved challenges. Synthesizing current research, including clinical trials and experimental models, bridges the gap between microbiome science and cancer therapy. Microbial metabolites such as short-chain fatty acids (SCFAs), polyamines, indoles, and bile acids play vital roles in regulating inflammation and suppressing cancer. Many metabolites exhibit potent anti-inflammatory and immunomodulatory effects, demonstrating therapeutic potential. Case studies show promising results, but challenges such as metabolite stability, bioavailability, and individual variability remain. Understanding microbiome-metabolite interactions offers novel strategies for cancer prevention and treatment. This review identifies knowledge gaps and proposes future research directions to harness microbiome-derived metabolites for innovative cancer therapies. Addressing these issues may pave the way for microbiome-targeted cancer interventions.
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Affiliation(s)
- Alice N. Mafe
- Department of Biological Sciences, Faculty of Sciences, Taraba State University, Main Campus, Jalingo 660101, Taraba State, Nigeria;
| | - Dietrich Büsselberg
- Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha Metropolitan Area, Al Rayyan P.O. Box 22104, Qatar
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Mejias-Luque R, Gerhard M. Decoding the interplay: Helicobacter pylori infection, tumor immune microenvironment, and immunotherapy outcomes in gastrointestinal cancers. Innovation (N Y) 2025; 6:100880. [PMID: 40432785 PMCID: PMC12105489 DOI: 10.1016/j.xinn.2025.100880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 03/10/2025] [Indexed: 05/29/2025] Open
Affiliation(s)
- Raquel Mejias-Luque
- Institute of Medical Microbiology, Immunology and Hygiene, Department Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
- German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany
| | - Markus Gerhard
- Institute of Medical Microbiology, Immunology and Hygiene, Department Preclinical Medicine, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
- German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany
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Abdeen SK, Mastandrea I, Stinchcombe N, Puschhof J, Elinav E. Diet-microbiome interactions in cancer. Cancer Cell 2025; 43:680-707. [PMID: 40185096 DOI: 10.1016/j.ccell.2025.03.013] [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: 01/07/2025] [Revised: 02/26/2025] [Accepted: 03/11/2025] [Indexed: 04/07/2025]
Abstract
Diet impacts cancer in diverse manners. Multiple nutritional effects on tumors are mediated by dietary modulation of commensals, residing in mucosal surfaces and possibly also within the tumor microenvironment. Mechanistically understanding such diet-microbiome-host interactions may enable to develop precision nutritional interventions impacting cancer development, dissemination, and treatment responses. However, data-driven nutritional strategies integrating diet-microbiome interactions are infrequently incorporated into cancer prevention and treatment schemes. Herein, we discuss how dietary composition affects cancer-related processes through alterations exerted by specific nutrients and complex foods on the microbiome. We highlight how dietary timing, including time-restricted feeding, impacts microbial function in modulating cancer and its therapy. We review existing and experimental nutritional approaches aimed at enhancing microbiome-mediated cancer treatment responsiveness while minimizing adverse effects, and address challenges and prospects in integrating diet-microbiome interactions into precision oncology. Collectively, mechanistically understanding diet-microbiome-host interactomes may enable to achieve a personalized and microbiome-informed optimization of nutritional cancer interventions.
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Affiliation(s)
- Suhaib K Abdeen
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
| | | | - Nina Stinchcombe
- Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Junior Research Group Epithelium Microbiome Interactions, DKFZ, Heidelberg, Germany
| | - Jens Puschhof
- Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany; Junior Research Group Epithelium Microbiome Interactions, DKFZ, Heidelberg, Germany.
| | - Eran Elinav
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany.
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Konishi H, Saito T, Takahashi S, Tanaka H, Okuda K, Akutsu H, Dokoshi T, Sakatani A, Takahashi K, Ando K, Kashima S, Ueno N, Moriichi K, Ogawa N, Fujiya M. The butyrate derived from probiotic Clostridium butyricum exhibits an inhibitory effect on multiple myeloma through cell death induction. Sci Rep 2025; 15:11919. [PMID: 40195469 PMCID: PMC11976985 DOI: 10.1038/s41598-025-97038-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Accepted: 04/02/2025] [Indexed: 04/09/2025] Open
Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by a poor prognosis. While certain probiotics have been shown to produce antitumor molecules that inhibit solid tumor progression, it remains unclear whether probiotic-derived compounds can exert similar effects on hematological tumors, such as MM. In this study, we screened the cell-free culture supernatants (CFCS) of 24 probiotic strains for antitumor effects against multiple myeloma (MM) cells and identified that the CFCS from Clostridium butyricum (C. butyricum) demonstrated the most significant reduction in MM cell viability. Further fractionation of this CFCS through reverse-phase and gel filtration chromatography revealed a high enrichment of butyrate in the antitumor fraction, as confirmed by gas chromatography-mass spectrometry. Butyrate reduced MM cell viability in a concentration-dependent manner. Butyrate was significantly more cytotoxic to RPMI-8226 cells than peripheral blood mononuclear cells (PBMCs) isolated from two non-cancerous individuals. In the xenograft model of RPMI-8226 cells, butyrate showed significant inhibition of tumor formation. Cell cycle analysis showed that butyrate induced G1 phase arrest and increased sub-G1 phase, suggesting DNA fragmentation. Western blot analysis demonstrated that butyrate treatment led to cleaved poly ADP-ribose polymerase (PARP) accumulation. Additionally, flow cytometry showed an increase in annexin V positive MM cells, indicating apoptosis. Butyrate also exhibited synergistic antitumor activity when combined with bortezomib, a proteasome inhibitor. These findings suggest that probiotic-derived molecules, including butyrate, may enhance the therapeutic effect of hematological malignancy, such as MM.
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Affiliation(s)
- Hiroaki Konishi
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
| | - Takeshi Saito
- Division of Hematology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Shuichiro Takahashi
- Division of Hematology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Hiroki Tanaka
- Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, 2-1 -1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Katsuhiro Okuda
- Department of Legal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Hiroaki Akutsu
- Central Laboratory for Research and Education, Research Technology Support Center, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Tatsuya Dokoshi
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
- Department of Gastroenterological Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Aki Sakatani
- Department of Gastroenterological Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Keitaro Takahashi
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Katsuyoshi Ando
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Shin Kashima
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Nobuhiro Ueno
- Department of Gastroenterological Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Kentaro Moriichi
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
- Department of Gastroenterological Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Naoki Ogawa
- Central Laboratory for Research and Education, Research Technology Support Center, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
| | - Mikihiro Fujiya
- Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
- Department of Gastroenterological Sciences, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido, 078-8510, Japan
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10
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Binienda A, Machelak W, Zielińska M, Fichna J. Free fatty acid receptors type 2 and 4 mediate the anticancer effects of fatty acids in colorectal cancer - in vitro and in vivo studies. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167708. [PMID: 39922546 DOI: 10.1016/j.bbadis.2025.167708] [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: 09/27/2024] [Revised: 01/14/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
High incidence of colorectal cancer (CRC) is influenced by diet low in fiber (source of short chain fatty acids, SCFAs, natural agonists for free fatty acid receptor type 2 (FFAR2)) and high in fat (main source of long chain fatty acids, LCFAs, FFAR4 agonists). FFAR2 and FFAR4 are downregulated in CRC. In this study, we characterized whether the anticancer effects of SCFAs and LCFAs are FFAR-dependent in in vitro and in vivo models of CRC. In vitro, SW-480 cell growth was determined after incubation with FFARs ligands (SCFAs: acetate, butyrate; LCFAs: palmitate, stearate) using MTT assay. Cell migration and invasion were investigated by wound healing and transwell-based invasion assays. In vivo, SCFAs and LCFAs were administered to azoxymethane/dextran sodium sulfate-treated mice. Real-time qPCR and Western blot were used to determine FFARs expression. SCFAs and LCFAs significantly decreased SW-480 cell growth, migration and invasion capacities. Combination of SCFAs and LCFAs induced synergistic inhibitory effects on CRC cell growth and motility. FFAR2 and FFAR4 expression were elevated in CRC cells treated with butyrate as well as with butyrate+acetate, and butyrate+palmitate+stearate. Concurrently, only FFAR4 expression was increased in CRC cells incubated with LCFAs. In vivo, treatment with LCFAs, but not SCFAs increased ffar2 and Ffar4 expression. Our findings showed that SCFAs and LCFAs inhibit cancer cell growth and their migration and invasion capabilities. Our study evidenced that the anticancer effects of SCFAs- and LCFAs are mediated by FFAR2 and FFAR4.
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Affiliation(s)
- Agata Binienda
- Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
| | - Weronika Machelak
- Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
| | - Marta Zielińska
- Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
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11
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Nehzomi ZS, Shirani K. The gut microbiota: A key player in cadmium toxicity - implications for disease, interventions, and combined toxicant exposures. J Trace Elem Med Biol 2025; 88:127570. [PMID: 39837257 DOI: 10.1016/j.jtemb.2024.127570] [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: 04/27/2024] [Revised: 10/24/2024] [Accepted: 11/20/2024] [Indexed: 01/23/2025]
Abstract
Cadmium (Cd) is a highly toxic heavy metal contaminant found in soil and water due to human activities such as mining and industrial discharge. Cd can accumulate in the body, leading to various health risks such as organ injuries, osteoporosis, renal dysfunction, Type 2 diabetes (T2DM), reproductive diseases, hypertension, cardiovascular diseases, and cancers. The gut is particularly sensitive to Cd toxicity as it acts as the primary barrier against orally ingested Cd. Even at low concentrations, Cd can cause oxidative stress, inflammation, and intestinal bleeding. Cd also disrupts the gut microbiota, affecting its structure, taxonomic composition, and metabolic functions. Cd exposure alters the structure of the gut microbial community, reducing diversity and upregulating certain phyla and genera. This disturbance can lead to physiological and metabolic imbalances, including disruptions in energy homeostasis, amino acid, lipid, nucleotide, and short-chain fatty acid (SCFAs) metabolism. The effects of Cd on the gut microbiota depend on the duration of exposure, the dose of Cd, and can vary based on sex and age. Cd-induced gut dysbiosis has been linked to various diseases, including diabetes, adiposity, atherosclerosis, liver damage, infections, cancer, and neurodegenerative diseases. Interventions targeting the gut microbiota, such as probiotics, specific diets, melatonin, selenium, vitamin D3, and certain compounds, have shown potential in reducing the health risks associated with Cd exposure. However, combined exposure to Cd and other toxicants, such as microplastics (MPs), heavy metals, and antibiotics, can amplify the toxicity and dysbiosis in the gut microbiota.
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Affiliation(s)
| | - Kobra Shirani
- Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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12
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Kharazi DM, Karam L, El Boustany C, Ibrahim JN. Sodium butyrate and sodium propionate inhibit breast cancer cell migration and invasion through regulation of epithelial-to-mesenchymal transition and suppression of MEK/ERK signaling pathway. Front Cell Dev Biol 2025; 13:1535563. [PMID: 40143970 PMCID: PMC11937081 DOI: 10.3389/fcell.2025.1535563] [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: 11/27/2024] [Accepted: 02/20/2025] [Indexed: 03/28/2025] Open
Abstract
Objective This study aims to investigate the roles played by NaB and NaP in breast carcinogenesis by elucidating their potential anti-metastatic effects in the context of tumor migration, invasion, and EMT regulation in two distinct breast cancer cell lines, MCF-7 and MDA-MB-231. Methods The cytotoxic effect of both compounds on 3D spheroid formation was evaluated using a hanging drop assay. The anti-migratory and anti-invasive potentials of NaB and NaP were investigated through transwell migration and invasion assays. Moreover, their role in regulating epithelial-to-mesenchymal transition (EMT) was examined by assessing E-cadherin, vimentin, and β-catenin mRNA and protein expression levels through RT-qPCR and Western blot or flow cytometry. β-Catenin localization upon treatment was further visualized via immunofluorescence. Protein expression of MEK, p-MEK, ERK, and p-ERK was analyzed by Western blot. Results Our results revealed a dose- and time-dependent impairment of spheroid formation in both cell lines, with NaB exerting a more potent effect than NaP. Both SCFAs were able to significantly inhibit migration and invasion of MDA-MB-231 cells following 24 h of treatment. Moreover, treatment with NaB or NaP altered the mRNA and protein profile of EMT-associated markers and abrogated the nuclear translocation of β-catenin. Finally, ERK and MEK phosphorylation was reduced in MDA-MB-231 and MCF-7 cells upon treatment with NaB, and less prominently with NaP. Conclusion Our study highlights the promising therapeutic potential of NaB and NaP, providing insight into their inhibitory effects on 3D formation, migration, and invasion through EMT regulation and deactivation of MEK/ERK signaling in breast cancer.
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Affiliation(s)
- Dania Mahmoud Kharazi
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon
| | - Louna Karam
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon
| | - Charbel El Boustany
- Department of Laboratory Science, Faculty of Public Health - Branch 2, Lebanese University, Fanar, Lebanon
| | - José-Noel Ibrahim
- Department of Biological Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon
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13
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Zhang C, Wang Y, Cheng L, Cao X, Liu C. Gut microbiota in colorectal cancer: a review of its influence on tumor immune surveillance and therapeutic response. Front Oncol 2025; 15:1557959. [PMID: 40110192 PMCID: PMC11919680 DOI: 10.3389/fonc.2025.1557959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/14/2025] [Indexed: 03/22/2025] Open
Abstract
Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.
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Affiliation(s)
- Chunlei Zhang
- Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Yong Wang
- Department of Hepatobiliary Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Lei Cheng
- Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Xiansheng Cao
- Department of Gastrointestinal Surgery, Hernia and Abdominal Wall Surgery I, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Chunyuan Liu
- Department of Colorectal and Anus Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
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14
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Świdnicka-Siergiejko A, Daniluk J, Miniewska K, Daniluk U, Guzińska-Ustymowicz K, Pryczynicz A, Dąbrowska M, Rusak M, Ciborowski M, Dąbrowski A. Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition. Cells 2025; 14:361. [PMID: 40072088 PMCID: PMC11898920 DOI: 10.3390/cells14050361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 02/22/2025] [Accepted: 02/27/2025] [Indexed: 03/15/2025] Open
Abstract
An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.
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Affiliation(s)
- Agnieszka Świdnicka-Siergiejko
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland; (J.D.); (A.D.)
| | - Jarosław Daniluk
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland; (J.D.); (A.D.)
| | - Katarzyna Miniewska
- Department of Medical Biochemistry, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | - Urszula Daniluk
- Department of Pediatrics, Gastroenterology, Hepatology, Nutrition, Allergology and Pulmonology, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | | | - Anna Pryczynicz
- Department of General Pathomorphology, Medical University of Bialystok, 15-276 Bialystok, Poland; (K.G.-U.); (A.P.)
| | - Milena Dąbrowska
- Department of Heamatological Diagnostics, Medical University of Bialystok, 15-276 Bialystok, Poland; (M.D.); (M.R.)
| | - Małgorzata Rusak
- Department of Heamatological Diagnostics, Medical University of Bialystok, 15-276 Bialystok, Poland; (M.D.); (M.R.)
| | - Michał Ciborowski
- Metabolomics and Proteomics Laboratory, Department of Medical Biochemistry, Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | - Andrzej Dąbrowski
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland; (J.D.); (A.D.)
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15
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Abbas M, Tangney M. The oncobiome; what, so what, now what? MICROBIOME RESEARCH REPORTS 2025; 4:16. [PMID: 40207280 PMCID: PMC11977386 DOI: 10.20517/mrr.2024.89] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/14/2025] [Accepted: 02/21/2025] [Indexed: 04/11/2025]
Abstract
Microbial communities inhabiting various body sites play critical roles in the initiation, progression, and treatment of cancer. The gut microbiota, a highly diverse microbial ecosystem, interacts with immune cells to modulate inflammation and immune surveillance, influencing cancer risk and therapeutic outcomes. Local tissue microbiota may impact the transition from premalignant states to malignancy. Characterization of the intratumoral microbiota increasingly reveals distinct microbiomes that may influence tumor growth, immune responses, and treatment efficacy. Various bacteria species have been reported to modulate cancer therapies through mechanisms such as altering drug metabolism and shaping the tumor microenvironment (TME). For instance, gut or intratumoral bacterial enzymatic activity can convert prodrugs into active forms, enhancing therapeutic effects or, conversely, inactivating small-molecule chemotherapeutics. Specific bacterial species have also been linked to improved responses to immunotherapy, underscoring the microbiome's role in treatment outcomes. Furthermore, unique microbial signatures in cancer patients, compared with healthy individuals, demonstrate the diagnostic potential of microbiota. Beyond the gut, tumor-associated and local microbiomes also affect therapy by influencing inflammation, tumor progression, and drug resistance. This review explores the multifaceted relationships between microbiomes and cancer, focusing on their roles in modulating the TME, immune activation, and treatment efficacy. The diagnostic and therapeutic potential of bacterial members of microbiota represents a promising avenue for advancing precision oncology and improving patient outcomes. By leveraging microbial biomarkers and interventions, new strategies can be developed to optimize cancer diagnosis and treatment.
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Affiliation(s)
- Munawar Abbas
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
- Cancer Research@UCC, University College Cork, Cork, T12 XF62, Ireland
| | - Mark Tangney
- APC Microbiome Ireland, University College Cork, Cork, T12 YT20, Ireland
- Cancer Research@UCC, University College Cork, Cork, T12 XF62, Ireland
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16
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Mivehchi H, Eskandari-Yaghbastlo A, Pour Bahrami P, Elhami A, Faghihinia F, Nejati ST, Kazemi KS, Nabi Afjadi M. Exploring the role of oral bacteria in oral cancer: a narrative review. Discov Oncol 2025; 16:242. [PMID: 40009328 DOI: 10.1007/s12672-025-01998-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 02/19/2025] [Indexed: 02/27/2025] Open
Abstract
A growing body of research indicates that a wide range of cancer types may correlate with human microbiome components. On the other hand, little is known about the potential contribution of the oral microbiota to oral cancer. However, some oral microbiome components can stimulate different tumorigenic processes associated with the development of cancer. In this line, two prevalent oral infections, Porphyromonas gingivalis, and Fusobacterium nucleatum can increase tumor growth. The microbiome can impact the course of the illness through direct interactions with the human body and major modifications to the toxicity and responsiveness to different kinds of cancer therapy. Recent research has demonstrated a relationship between specific phylogenetic groupings and the results of immunotherapy treatment for particular tumor types. Conversely, there has been a recent upsurge in interest in the possibility of using microbes to treat cancer. At the moment, some species, such as Salmonella typhimurium and Clostridium spp., are being explored as possible cancer treatment vectors. Thus, understanding these microbial interactions highlights the importance of maintaining a healthy oral microbiome in preventing oral cancers. From this perspective, this review will discuss the role of the microbiome on oral cancers and their possible application in oral cancer treatment/improvement.
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Affiliation(s)
- Hassan Mivehchi
- Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | | | | | - Anis Elhami
- Faculty of Dentistry, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farbod Faghihinia
- School of Dentistry, Yasuj University of Medical Sciences, Yasuj, Iran
| | | | - Kimia Sadat Kazemi
- Faculty of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohsen Nabi Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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17
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许 欣, 郭 丽, 郑 康, 马 燕, 林 淑, 何 盈, 盛 雯, 许 素, 邱 峰. [ Lacticaseibacillus paracasei E6 improves vinorelbine-induced immunosuppression in zebrafish through its metabolites acetic acid and propionic acid]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2025; 45:331-339. [PMID: 40031977 PMCID: PMC11875848 DOI: 10.12122/j.issn.1673-4254.2025.02.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Indexed: 03/05/2025]
Abstract
OBJECTIVES To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish. METHODS The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression. RESULTS After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells. CONCLUSIONS L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.
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Affiliation(s)
| | | | | | | | | | | | | | | | - 峰 邱
- 邱 峰，博士，主任技师，博士生导师，E-mail:
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18
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Yang P, Bai H, Yan T, Xu X, Tang X, Song B, Liu Y, Lu Y, Liu P, Tu W, Shi Y, Zhang S. Integrative multi-omics analysis of radionuclide-induced intestinal injury reveals the radioprotective role of L-citrulline through histone H3-mediated Cxcl3. J Transl Med 2025; 23:180. [PMID: 39953550 PMCID: PMC11829450 DOI: 10.1186/s12967-025-06197-9] [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: 09/19/2024] [Accepted: 02/03/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND The widespread application of nuclear technology has markedly heightened the risk of extensive, uncontrolled exposure to radiation. Nevertheless, in contrast to external irradiation, the biological impacts and countermeasures against internal irradiation from radionuclides remain inadequately characterized. METHODS Mice were administered yttrium-90 (Y90) carbon microspheres via gavage at different dosages (0-5.0 mCi) to establish a radionuclides exposure model. A multi-omics analysis was employed to access alterations in gut microbiota, fecal and colonic metabolites profiles, and intestinal mRNA expression post-irradiation. The function of significant metabolite was validated at both cellular levels and organismal levels. Additionally, ChIP-Seq and RNA-Seq techniques were utilized to investigate the molecular mechanism underlying the actions of key metabolite. RESULTS Exposure to Y90 resulted in intestinal damage and hematological impairment. Multi-omics analysis revealed significant alternations of gut microbiota, fecal metabolites, colonic metabolites, and intestinal mRNA expression following internal radiation exposure. Notably, L-citrulline was identified as a metabolite with changes observed in both fecal and colonic tissues, demonstrating radioprotective properties in vitro and in vivo. Mechanistically, L-citrulline facilitated the citrullination of histone H3 at the 17th site (H3Cit17), and multiple mRNAs including C-X-C motif chemokine ligand 3 (Cxcl3), were transcriptionally regulated by H3Cit17 post L-citrulline treatment. Furthermore, Cxcl3 conferred protective effects for intestinal epithelial cells against ionizing radiation. CONCLUSIONS The research offers critical perspectives on the intestinal and gut microbiota's reaction to radionuclides exposure. It underscores the promise of L-citrulline as a radioprotective compound, which may have substantial ramifications for the formulation of strategies to mitigate radiation exposure.
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Affiliation(s)
- Ping Yang
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Hao Bai
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Tao Yan
- The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China
| | - Xiaopeng Xu
- Department of Gastroenterology, the Jiangyin Clinical College of Xuzhou Medical University, Jiangyin, 214400, China
| | - Xiaoyou Tang
- Medical College of Tibet University, Lasa, 850000, China
| | - Bin Song
- West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Yulan Liu
- The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China
| | - Yunyun Lu
- Radiochemical Laboratory, Reactor Operation and Application Research Sub-Institute, Nuclear Power Institute of China, Chengdu, 610200, China
| | - Pengfei Liu
- Department of Gastroenterology, the Jiangyin Clinical College of Xuzhou Medical University, Jiangyin, 214400, China
| | - Wenling Tu
- The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China
| | - Yuhong Shi
- The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China
| | - Shuyu Zhang
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China.
- The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China.
- Medical College of Tibet University, Lasa, 850000, China.
- West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
- NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, 621099, China.
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19
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Mafe AN, Büsselberg D. Modulation of the Neuro-Cancer Connection by Metabolites of Gut Microbiota. Biomolecules 2025; 15:270. [PMID: 40001573 PMCID: PMC11853082 DOI: 10.3390/biom15020270] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 02/10/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, and cancer progression. Recent advances have accentuated the significant role of gut microbiota metabolites in modulating systemic processes that influence both brain health and tumorigenesis. This paper explores the emerging concept of metabolite-mediated modulation within the gut-brain-cancer connection, focusing on key metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, and lipopolysaccharides (LPS). While the gut microbiota's impact on immune regulation, neuroinflammation, and tumor development is well established, gaps remain in grasping how specific metabolites contribute to neuro-cancer interactions. We discuss novel metabolites with potential implications for neurobiology and cancer, such as indoles and polyamines, which have yet to be extensively studied. Furthermore, we review preclinical and clinical evidence linking gut dysbiosis, altered metabolite profiles, and brain tumors, showcasing limitations and research gaps, particularly in human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal microbiota transplantation, and probiotics, demonstrate promise but also indicate hurdles in translating these findings to clinical cancer therapies. This paper concludes with a call for standardized multi-omics approaches and bi-directional research frameworks integrating microbiome, neuroscience, and oncology to develop personalized therapeutic strategies for neuro-cancer patients.
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Affiliation(s)
- Alice N. Mafe
- Department of Biological Sciences, Faculty of Sciences, Taraba State University, Main Campus, Jalingo 660101, Taraba State, Nigeria;
| | - Dietrich Büsselberg
- Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha Metropolitan Area, Doha P.O. Box 22104, Qatar
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20
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Fu Q, Yang Y, Tian Q, Zhu Y, Xu H, Wang J, Huang Q. Exploring the mechanism of Paotianxiong polysaccharide in the treatment of chronic kidney disease combining metabolomics and microbiomics technologies. Int J Biol Macromol 2025; 289:138629. [PMID: 39667450 DOI: 10.1016/j.ijbiomac.2024.138629] [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: 02/15/2024] [Revised: 11/30/2024] [Accepted: 12/09/2024] [Indexed: 12/14/2024]
Abstract
A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.
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Affiliation(s)
- Qinwen Fu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Yu Yang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Qingqing Tian
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Ying Zhu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Huiyuan Xu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China
| | - Jin Wang
- College of Ethnic Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
| | - Qinwan Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China.
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21
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Wu XR, He XH, Xie YF. Characteristics of gut microbiota dysbiosis in patients with colorectal polyps. World J Gastrointest Oncol 2025; 17:98872. [PMID: 39817124 PMCID: PMC11664624 DOI: 10.4251/wjgo.v17.i1.98872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/05/2024] [Accepted: 09/19/2024] [Indexed: 12/12/2024] Open
Abstract
This editorial, inspired by a recent study published in the World Journal of Gastrointestinal Oncology, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of Klebsiella, Parvimonas, and Clostridium increase, while those of Bifidobacterium and Lactobacillus decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.
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Affiliation(s)
- Xian-Rong Wu
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
| | - Xiao-Hong He
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
| | - Yong-Fang Xie
- School of Life Health Information Science and Engineering, Chongqing Post and Communications University, Chongqing 400065, China
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22
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Gardiner B, Wardill HR, O'Connor G, Hargrave D, Lett AM. The impact of fibre and prebiotic interventions on outcomes in cancer and haematopoietic stem cell transplantation: A systematic review. Clin Nutr 2025; 44:86-100. [PMID: 39644740 DOI: 10.1016/j.clnu.2024.11.022] [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: 06/09/2024] [Revised: 10/26/2024] [Accepted: 11/10/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND & AIMS Cancer therapy is associated with a range of toxicities that severely impact patient well-being and a range of clinical outcomes. Dietary fibre/prebiotics characteristically improve the gastrointestinal microenvironment, which consequently elicits beneficial downstream effects that could be relevant to the prevention and management of treatment-related toxicities. Despite the compelling theoretical scientific rationale there has been limited effort to synthesise the available evidence to conclude such scientific underpinning to the clinical use of fibre/prebiotics in cancer patients. Therefore, this systematic review aimed to evaluate the clinical impact of fibre/prebiotic-based interventions on gastrointestinal-side effects; gastrointestinal-microbiome; clinical outcomes; nutrition status and body composition; and quality-of-life in children and adults being treated for cancer or undergoing a haematopoietic stem cell transplant (HSCT). METHODS This study was conducted in adherence to PRISMA guidelines, and the protocol was published prospectively with PROSPERO (CRD42022299428). Three databases (MEDLINE (Ovid), CINHAL, EMBASE) were searched from inception to December 2023. All articles were assessed for bias using the Cochrane risk-of-bias tool RoB 2.0 (for RCTs) and ROBINS-I (for non-RCTs). RESULTS A total of 9989 de-duplicated records were identified, of these, 14 (paediatrics [n = 1], adults [n = 13]) met the inclusion criteria (randomised controlled trials (RCT) [n = 11], observational or non-RCTs [n = 3]). The risk-of-bias was graded to be serious/high (n = 6); moderate/some concerns (n = 7); low (n = 1). Interventions included prebiotic supplement (n = 8), nutrition supplement/formula with added fibre/prebiotic (n = 3) and dietary modification (n = 3). The dose of fibre intervention ranged from 2.4g to 30g per day. Substantial heterogeneity of target parameters was identified across a range all outcome categories, precluding definitive conclusions. CONCLUSION The scientific rationale for fibre/prebiotics-based interventions for the prevention or management of cancer treatment-related toxicities is compelling. However, it is clear that the scientific and clinical field remains disconnected in how to effectively translate this approach to improve cancer outcomes. High-quality intervention studies translatable to clinical practice are now evidently crucial to determine if and how fibre/prebiotics should be used to support people undergoing cancer or HSCT therapy.
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Affiliation(s)
- Breeana Gardiner
- Department of Nutrition and Dietetics, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH, UK; Section of Nutrition, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
| | - Hannah R Wardill
- School of Biomedicine, The University of Adelaide, Adelaide, South Australia, 5005, Australia; Supportive Oncology Research Group, Precision Cancer Medicine, South Australian Health and Medical Research Institute, Adelaide, South Australia, 5000, Australia.
| | - Graeme O'Connor
- Department of Nutrition and Dietetics, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH, UK. graeme.o'
| | - Darren Hargrave
- Department of Paediatric Oncology, Great Ormond Street Hospital London, London, WC1N 3JH, UK; UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, WC1N 1EH, UK.
| | - Aaron M Lett
- Section of Nutrition, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, W12 0NN, UK.
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23
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Nami Y, Barghi A, Shahgolzari M, Salehian M, Haghshenas B. Mechanism of Action and Beneficial Effects of Probiotics in Amateur and Professional Athletes. Food Sci Nutr 2025; 13:e4658. [PMID: 39803224 PMCID: PMC11717059 DOI: 10.1002/fsn3.4658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 11/09/2024] [Accepted: 11/25/2024] [Indexed: 01/16/2025] Open
Abstract
Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. According to the International Society of Sports Nutrition (ISSN), probiotic supplementation can optimize the health, performance, and recovery of athletes at all stages of their careers. Recent research suggests that probiotics can improve immune system functions, reduce gastrointestinal distress, and increase gut permeability in athletes. Additionally, probiotics may provide athletes with secondary health benefits that could positively affect athletic performance through enhanced recovery from fatigue, improved immune function, and maintenance of healthy gastrointestinal tract function. The integration of some probiotic strains into athletes' diets and the consumption of multi-strain compounds may lead to an improvement in performance and can positively affect performance-related aspects such as fatigue, muscle pain, body composition, and cardiorespiratory fitness. In summary, probiotics can be beneficial for athletes at all stages of their careers, from amateur to professional. This paper reviews the progress of research on the role of probiotic supplementation in improving energy metabolism and immune system functions, reducing gastrointestinal distress, and enhancing recovery from fatigue in athletes at different levels.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest and West RegionAgricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)TabrizIran
| | - Anahita Barghi
- Institute of Agricultural Life ScienceDong‐A UniversityBusanSouth Korea
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
- Biotechnology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Melika Salehian
- Student Research CommitteeKermanshah University of Medical SciencesKermanshahIran
| | - Babak Haghshenas
- Regenerative Medicine Research Center (RMRC), Health Technology InstituteKermanshah University of Medical SciencesKermanshahIran
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24
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D’Antonio DL, Zenoniani A, Umme S, Piattelli A, Curia MC. Intratumoral Fusobacterium nucleatum in Pancreatic Cancer: Current and Future Perspectives. Pathogens 2024; 14:2. [PMID: 39860963 PMCID: PMC11768203 DOI: 10.3390/pathogens14010002] [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: 12/02/2024] [Revised: 12/22/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
The intratumoral microbiome plays a significant role in many cancers, such as lung, pancreatic, and colorectal cancer. Pancreatic cancer (PC) is one of the most lethal malignancies and is often diagnosed at advanced stages. Fusobacterium nucleatum (Fn), an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in several extra-oral human diseases and, lately, in pancreatic cancer progression and prognosis. It is now recognized as oncobacterium. Fn engages in pancreatic tumorigenesis and metastasis through multifaceted mechanisms, including immune response modulation, virulence factors, control of cell proliferation, intestinal metabolite interactions, DNA damage, and epithelial-mesenchymal transition. Additionally, compelling research suggests that Fn may exert detrimental effects on cancer treatment outcomes. This paper extends the perspective to pancreatic cancer associated with Fn. The central focus is to unravel the oncogenomic changes driven by Fn in colonization, initiation, and promotion of pancreatic cancer development. The presence of Fusobacterium species can be considered a prognostic marker of PC, and it is also correlated to chemoresistance. Furthermore, this review underscores the clinical research significance of Fn as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment. It is thought that given the role of Fn in tumor formation and metastasis processes via its FadA, FapA, Fap2, and RadD, new therapies for tumor treatment targeting Fn will be developed.
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Affiliation(s)
- Domenica Lucia D’Antonio
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy; (D.L.D.); (A.Z.); (S.U.)
| | - Anna Zenoniani
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy; (D.L.D.); (A.Z.); (S.U.)
| | - Samia Umme
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy; (D.L.D.); (A.Z.); (S.U.)
- Department of Neuroscience, Imaging and Clinical Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy
| | - Adriano Piattelli
- School of Dentistry, Saint Camillus International University of Health and Medical Sciences (UniCamillus), 00131 Rome, Italy;
- Facultad de Medicina, UCAM Universidad Católica San Antonio de Murcia, 30107 Murcia, Spain
| | - Maria Cristina Curia
- Department of Medical, Oral and Biotechnological Sciences, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy; (D.L.D.); (A.Z.); (S.U.)
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25
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Yang S, Hao S, Ye H, Zhang X. Crosstalk between gut microbiota and cancer chemotherapy: current status and trends. Discov Oncol 2024; 15:833. [PMID: 39715958 DOI: 10.1007/s12672-024-01704-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 12/13/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Chemotherapy is crucial in the management of tumors, but challenges such as chemoresistance and adverse reactions frequently lead to therapeutic delays or even premature cessation. A growing body of research underscores a profound connection between the gut microbiota (GM) and cancer chemotherapy (CC). This paper aims to pinpoint highly influential publications and monitor the current landscape and evolving trends within the realm of GM/CC research. METHODS On October 1st, 2024, a comprehensive search for GM/CC publications spanning the past 20 years from 2004 to 2023 was conducted utilizing the Web of Science Core Collection (WoSCC). The scope encompassed both articles and reviews, and the data was subsequently extracted. To gain insights into the evolution and dynamics of this research field, we employed bibliometric analysis tools such as the Bibliometrix R package, VOSviewer, and Microsoft Excel to visualize and analyze various dimensions, including prominent journals, leading authors, esteemed institutions, contributing countries/regions, highly cited papers, and frequently occurring keywords. RESULTS A total of 888 papers were obtained. The number of publications about GM/CC studies has increased gradually. China and the United States published the largest number of papers. The INSERM was in the leading position in publishers. The most productive authors were Zitvogel L from France. Cancers had the largest number of papers. Citation analysis explained the historical evolution and breakthroughs in GM/CC research. Highly cited papers and common keywords illustrated the status and trends of GM/CC research. Four clusters were identified, and the hot topics included the role of the GM in the efficacy and toxicity of CC, the targeting of the GM to improve the outcome of CC, the mechanism by which the GM affects CC, and the correlation of the GM with carcinogenesis and cancer therapy. Metabolism, GM-derived metabolites, tumor microenvironment, immunity, intestinal barrier, tumor microbiota and Fusobacterium nucleatum may become the new hotspots and trends of GM/CC research. CONCLUSION This study analyzed global publications and bibliometric characteristics of the links between GM and CC, identified highly cited papers in GM/CC, provided insight into the status, hotspots, and trends of global GM/CC research, and showed that the GM can be used to predict the efficacy and toxicity of CC and modifying the GM can improve the outcomes of chemotherapeutics, which may inform clinical researchers of future directions.
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Affiliation(s)
- Shanshan Yang
- Department of Traditional Chinese Medicine, Peking University First Hospital, Beijing, China
| | - Shaodong Hao
- Spleen-Stomach Department, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Ye
- Department of Traditional Chinese Medicine, Peking University First Hospital, Beijing, China.
| | - Xuezhi Zhang
- Department of Traditional Chinese Medicine, Peking University First Hospital, Beijing, China.
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26
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Mir R, Albarqi SA, Albalawi W, Alatwi HE, Alatawy M, Bedaiwi RI, Almotairi R, Husain E, Zubair M, Alanazi G, Alsubaie SS, Alghabban RI, Alfifi KA, Bashir S. Emerging Role of Gut Microbiota in Breast Cancer Development and Its Implications in Treatment. Metabolites 2024; 14:683. [PMID: 39728464 DOI: 10.3390/metabo14120683] [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: 10/15/2024] [Revised: 11/14/2024] [Accepted: 11/25/2024] [Indexed: 12/28/2024] Open
Abstract
Background: The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer. Emerging evidence indicates that the gut microbiota affects the response to anticancer therapies by modulating the host immune system. Recent studies have explained a high correlation between the gut microbiota and breast cancer: dysbiosis in breast cancer may regulate the systemic inflammatory response, hormone metabolism, immune response, and the tumor microenvironment. Some of the gut bacteria are related to estrogen metabolism, which may increase or decrease the risk of breast cancer by changing the number of hormones. Further, the gut microbiota has been seen to modulate the immune system in respect of its ability to protect against and treat cancers, with a specific focus on hormone receptor-positive breast cancer. Probiotics and other therapies claiming to control the gut microbiome by bacterial means might be useful in the prevention, or even in the treatment, of breast cancer. Conclusions: The present review underlines the various aspects of gut microbiota in breast cancer risk and its clinical application, warranting research on individualized microbiome-modulated therapeutic approaches to breast cancer treatment.
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Affiliation(s)
- Rashid Mir
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research Chair for Biomedical Research, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Shrooq A Albarqi
- Molecular Medicine, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Wed Albalawi
- Molecular Medicine, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Hanan E Alatwi
- Department of Biology, Faculty of Science, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Marfat Alatawy
- Department of Biology, Faculty of Science, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Ruqaiah I Bedaiwi
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research Chair for Biomedical Research, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Reema Almotairi
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research Chair for Biomedical Research, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Eram Husain
- Department of Medical Lab Technology, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research Chair for Biomedical Research, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Mohammad Zubair
- Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Ghaida Alanazi
- Molecular Medicine, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Shouq S Alsubaie
- Molecular Medicine, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Razan I Alghabban
- Molecular Medicine, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 47713, Saudi Arabia
| | - Khalid A Alfifi
- Department of Laboratory and Blood Bank, King Fahd Special Hospital, Tabuk 47717, Saudi Arabia
| | - Shabnam Bashir
- Mubarak Hospital, Srinagar 190002, Jammu and Kashmir, India
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27
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Kalyanaraman B, Cheng G, Hardy M. The role of short-chain fatty acids in cancer prevention and cancer treatment. Arch Biochem Biophys 2024; 761:110172. [PMID: 39369836 PMCID: PMC11784870 DOI: 10.1016/j.abb.2024.110172] [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: 08/15/2024] [Revised: 09/25/2024] [Accepted: 10/03/2024] [Indexed: 10/08/2024]
Abstract
Short-chain fatty acids (SCFAs) are microbial metabolites in the gut that may play a role in cancer prevention and treatment. They affect the metabolism of both normal and cancer cells, regulating various cellular energetic processes. SCFAs also inhibit histone deacetylases, which are targets for cancer therapy. The three main SCFAs are acetate, propionate, and butyrate, which are transported into cells through specific transporters. SCFAs may enhance the efficacy of chemotherapeutic agents and modulate immune cell metabolism, potentially reprogramming the tumor microenvironment. Although SCFAs and SCFA-generating microbes enhance therapeutic efficacy of several forms of cancer therapy, published data also support the opposing viewpoint that SCFAs mitigate the efficacy of some cancer therapies. Therefore, the relationship between SCFAs and cancer is more complex, and this review discusses some of these aspects. Clearly, further research is needed to understand the role of SCFAs, their mechanisms, and applications in cancer prevention and treatment.
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Affiliation(s)
- Balaraman Kalyanaraman
- Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, United States.
| | - Gang Cheng
- Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, United States
| | - Micael Hardy
- Aix-Marseille Univ, CNRS, ICR, UMR 7273, Marseille, 13013, France
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28
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Nataraj BH, Ranveer SA, K J, Nagpal R, Behare PV. Immune and microbiome modulatory effects of Limosilactobacillus fermentum NCDC 400 in an immunocompromised mouse model. Microb Pathog 2024; 196:106927. [PMID: 39265811 DOI: 10.1016/j.micpath.2024.106927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 08/22/2024] [Accepted: 09/09/2024] [Indexed: 09/14/2024]
Abstract
The present study was aimed to assess and validate the safety and functional efficacy of an indigenous probiotic strain Limosilactobacillus fermentum NCDC 400 (hereafter, LFN400) in an immunocompromised murine model. The study included four groups; a normal control (NC) group without immune suppression; an experimental model control (MC) with immune suppression induced via intraperitoneal cyclophosphamide (Cy) administration; and two MC groups orally administered with either low dose (LD) or high dose (HD) of LFN400 at dose 108 and 1010 CFU/mouse/day, respectively, for 15-days. Both control groups received normal saline as placebo control. LFN400 improved specific experimental characteristics including hematological and serum biochemical markers. Compared to MC group, LFN400-fed groups showed markedly (P < 0.05) decreased arrays of detrimental caecal enzymes. We did not observe instances of bacterial translocation of LFN400 from gut to bloodstream or extra-intestinal organs. LFN400 intake significantly (P < 0.05) enhanced spleen cell differentiation, immune and oxidative stress markers, and restored Cy-induced histopathological changes in multiple tissues, including the spleen. There was no genotoxic effect of LFN400 on bone marrow cells. Although not statistically significant, LFN400 feeding moderately increased gut microbiome diversity, supporting the growth of beneficial saccharolytic microorganisms and reducing the presence of pathobionts. The findings demonstrate that the probiotic strain LFN400 possesses in vivo safety and immunomodulatory potency and thus should be considered a potential candidate for future human clinical studies.
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Affiliation(s)
- Basavaprabhu Haranahalli Nataraj
- Techno-functional Starter Lab, National Collection of Dairy Cultures (NCDC), Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, 132001, Haryana, India; Dairy Bacteriology Section, Southern Regional Station (SRS), ICAR-National Dairy Research Institute, Adugodi, Bengaluru, 560 030, Karnataka, India.
| | - Soniya A Ranveer
- Techno-functional Starter Lab, National Collection of Dairy Cultures (NCDC), Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, 132001, Haryana, India.
| | - Jeevan K
- Regional Ayurveda Research Institute, Central Council for Research in Ayurvedic Sciences, Aamkho, Gwalior, 474009, Madhya Pradesh, India.
| | - Ravinder Nagpal
- The Gut Biome Lab, Department of Health, Nutrition, and Food Sciences, Florida State University, Tallahassee, FL, 32306, USA.
| | - Pradip V Behare
- Techno-functional Starter Lab, National Collection of Dairy Cultures (NCDC), Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, 132001, Haryana, India.
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Herrera-Quintana L, Vázquez-Lorente H, Silva RCMC, Olivares-Arancibia J, Reyes-Amigo T, Pires BRB, Plaza-Diaz J. The Role of the Microbiome and of Radiotherapy-Derived Metabolites in Breast Cancer. Cancers (Basel) 2024; 16:3671. [PMID: 39518108 PMCID: PMC11545256 DOI: 10.3390/cancers16213671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/25/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
The gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, the interplay between the microbiome and radiotherapy-derived metabolites may enhance therapeutic outcomes and minimize adverse effects. In this review, we explore the bidirectional relationship between the gut microbiome and breast cancer. We explain how gut microbiome composition influences cancer progression and treatment response, and how breast cancer and its treatments influence microbiome composition. A dual role for radiotherapy-derived metabolites is explored in this article, highlighting both their therapeutic benefits and potential hazards. By integrating genomics, metabolomics, and bioinformatics tools, we present a comprehensive overview of these interactions. The study provides real-world insight through case studies and clinical trials, while therapeutic innovations such as probiotics, and dietary interventions are examined for their potential to modulate the microbiome and enhance treatment effectiveness. Moreover, ethical considerations and patient perspectives are discussed, ensuring a comprehensive understanding of the subject. Towards revolutionizing treatment strategies and improving patient outcomes, the review concludes with future research directions. It also envisions integrating microbiome and metabolite research into personalized breast cancer therapy.
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Affiliation(s)
- Lourdes Herrera-Quintana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Héctor Vázquez-Lorente
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | | | - Jorge Olivares-Arancibia
- AFySE Group, Research in Physical Activity and School Health, School of Physical Education, Faculty of Education, Universidad de Las Américas, Santiago 7500975, Chile;
| | - Tomás Reyes-Amigo
- Physical Activity Sciences Observatory (OCAF), Department of Physical Activity Sciences, Universidad de Playa Ancha, Valparaíso 2360072, Chile;
| | - Bruno Ricardo Barreto Pires
- Biometry and Biophysics Department, Institute of Biology Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20551-030, RJ, Brazil;
| | - Julio Plaza-Diaz
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- School of Health Sciences, Universidad Internacional de La Rioja, Avenida de la Paz, 137, 26006 Logroño, Spain
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Xu Y, Wu X, Li Y, Liu X, Fang L, Jiang Z. Probiotics and the Role of Dietary Substrates in Maintaining the Gut Health: Use of Live Microbes and Their Products for Anticancer Effects against Colorectal Cancer. J Microbiol Biotechnol 2024; 34:1933-1946. [PMID: 39210613 PMCID: PMC11540615 DOI: 10.4014/jmb.2403.03056] [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: 03/27/2024] [Revised: 07/19/2024] [Accepted: 07/28/2024] [Indexed: 09/04/2024]
Abstract
The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.
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Affiliation(s)
- Yi Xu
- Phase I Clinical Cancer Trial Center, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, P.R. China
| | - Xiahui Wu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Yan Li
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Xuejie Liu
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Lijian Fang
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
| | - Ziyu Jiang
- Phase I Clinical Cancer Trial Center, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, P.R. China
- Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222002, P.R. China
- Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang 222002, P.R. China
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Pan L, Yin N, Duan M, Mei Q, Zeng Y. The role of gut microbiome and its metabolites in pancreatitis. mSystems 2024; 9:e0066524. [PMID: 39212377 PMCID: PMC11494936 DOI: 10.1128/msystems.00665-24] [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] [Indexed: 09/04/2024] Open
Abstract
Gut microbiome plays a vital role in the intestinal ecosystem and has close association with metabolites. Due to the development of metabolomics and microbiomics, recent studies have observed that alteration of either the gut microbiome or metabolites may have effects on the progression of pancreatitis. Several new treatments based on the gut microbiome or metabolites have been studied extensively in recent years. Gut microbes, such as Bifidobacterium, Akkermansia, and Lactobacillus, and metabolites, such as short-chain fatty acids, bile acids, vitamin, hydrogen sulfide, and alcohol, have different effects on pancreatitis. Some preliminary studies about new intervention measures were based on the gut microbiome and metabolites such as diet, prebiotic, herbal medicine, and fecal microbiota transplantation. This review aims to summarize the recent advances about the gut microbiome, metabolites, and pancreatitis in order to determine the potential beneficial role of the gut microbiome and metabolites in pancreatitis.
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Affiliation(s)
- Letian Pan
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Nuoming Yin
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Mingyu Duan
- Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Qixiang Mei
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yue Zeng
- Shanghai Key Laboratory of Pancreatic Disease, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
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32
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Gomez CB, Mitchell J, Marks BP. A decision analysis of cancer patients and the consumption of ready-to-eat salad. RISK ANALYSIS : AN OFFICIAL PUBLICATION OF THE SOCIETY FOR RISK ANALYSIS 2024. [PMID: 39389932 DOI: 10.1111/risa.17658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 07/25/2024] [Accepted: 08/14/2024] [Indexed: 10/12/2024]
Abstract
Listeria monocytogenes is a foodborne pathogen of concern for cancer patients, who face higher morbidity and mortality rates than the general population. The neutropenic diet (ND), which excludes fresh produce, is often utilized to mitigate this risk; however, an analysis weighing the theoretical listeriosis risk reduction of produce exclusion aspects of the ND and possible negative tradeoffs has never been conducted. Consequently, this work constructed decision analytic models using disability-adjusted life years (DALYs) to compare the impacts of the ND, such as increased neutropenic enterocolitis (NEC) likelihood, with three alternative dietary practices (safe food handling [SFH], surface blanching, and refrigeration only) across five age groups, for cancer patients who consume ready-to-eat salad. Less disruptive diets had fewer negative health impacts in all scenarios, with median alternative diet DALYs per person per chemotherapy cycle having lower values in terms of negative health outcomes (0.088-0.443) than the ND (0.619-3.102). DALYs were dominated by outcomes associated with NEC, which is more common in patients following the ND than in other diets. Switchover point analysis confirmed that, because of this discrepancy, there were no feasible values of other parameters that could justify the ND. Correspondingly, the sensitivity analysis indicated that NEC mortality rate and remaining life expectancy strongly affected DALYs, further illustrating the model's strong dependence on NEC outcomes. Given these findings, and the SFH's ease of implementation and high compliance rates, the SFH diet is recommended in place of the ND.
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Affiliation(s)
- Carly B Gomez
- Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, Michigan, USA
| | - Jade Mitchell
- Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, Michigan, USA
| | - Bradley P Marks
- Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, Michigan, USA
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Deng J, Deng D, Wang B, Donati V, Frampton AE, Giovannetti E. Metabolites derived from gut microbiota mitigate chemoresistance in pancreatic cancer. Expert Rev Gastroenterol Hepatol 2024; 18:597-604. [PMID: 39439262 DOI: 10.1080/17474124.2024.2412045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 09/30/2024] [Indexed: 10/25/2024]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of tumor-related deaths. The gut microbiota has gained attention in cancer treatment, due to its influence on the immune system and drug activity. AREAS COVERED Tintelnot and collaborators highlight distinct gut microbiota composition in metastatic PDAC (mPDAC) patients responding versus non-responding to chemotherapy. In the context of chemotherapy treatment, the gut microbiota of responders can metabolize tryptophan from food into indole-3-acetic acid (3-IAA). The presence of neutrophil-derived myeloperoxidase facilitates the role of 3-IAA in promoting the accumulation of reactive oxygen species in tumor cells. This accumulation, in turn, inducing tumor cell cytotoxicity. Additionally, 3-IAA can inhibit tumor cell autophagy activity, diminishing tumor cells' ability to adapt to cell stress. This manuscript provides a comprehensive analysis of the latest research on microbiota, metabolites, and PDAC, sourced from PubMed, ScienceDirect, and Google Scholar. EXPERT OPINION The evaluated study noted an elevation of the bacterial metabolite 3-IAA in responsive PDAC patients' serum, suggesting its potential to enhance chemotherapy sensitivity. Gaining a thorough comprehension of the impact of gut microbiota metabolites on drug activity is beneficial for broadening our strategies to mitigate chemotherapy resistance in tumors and identifying markers that predict chemotherapy outcomes.
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Affiliation(s)
- Juan Deng
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Dongmei Deng
- Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands
| | - Bing Wang
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Valentina Donati
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Unit of Pathological Anatomy 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Adam E Frampton
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
- Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Medical Science, University of Surrey, Guilford, UK
| | - Elisa Giovannetti
- Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Cancer Pharmacology Lab, Fondazione Pisana per la Scienza, San Giuliano, Pisa, Italy
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Kumar Mahanta S, Pratikshya Nayak P, Muduli K, Elangovan S, Paramasivan SS, Kumar Mallick P, Kumar Mohapatra S, Kumar Panda S. Optimisation ofLevilactobacillus brevis-fermented finger millet (Eleusine coracana) and evaluation of its effects on cancer cells (HCT116 and MDA-MB-231). Methods 2024; 229:30-40. [PMID: 38880434 DOI: 10.1016/j.ymeth.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/27/2024] [Accepted: 06/06/2024] [Indexed: 06/18/2024] Open
Abstract
The objective of this study was to optimise the millet formulation using Levilactobacillus brevis and to evaluate its anticarcinogenic potential in vitro. The formula was developed in the course of the fermentation of finger millet (Eleusine coracana) using L. brevis MTTC 4460 and optimised by response surface methodology and validation by artificial neural networking (ANN). The optimised millet formulation could be obtained using 2 % of bacterial inoculum, 2 % of glucose, and a fermentation duration of 3.3 days with a yield of 5.98 mg/mL lactic acid and 3.38 log10 (CFU/mL) viable L. brevis with overall desirability value of 1. The fermented millet formulation exhibited antiproliferative and antimigratory effects on MDA-MB-231 and HCT116 cancer cell lines. In addition, the outcomes observed in western blot analysis revealed that the formulation elicited apoptotic responses mediated by the Bcl-2 family of proteins in MDA-MB-231 and HCT116 cell lines while demonstrating no discernible impact on HEK293 normal cells.
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Affiliation(s)
- Sachin Kumar Mahanta
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India
| | - Priyadarshini Pratikshya Nayak
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India
| | - Kartik Muduli
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India
| | - Selvakumar Elangovan
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India
| | - Sethuraman Sivakumar Paramasivan
- Section of Extension and Social Sciences, ICAR - Central Tuber Crops Research Institute, Thiruvananthapuram - 695017, Kerala, India
| | - Pradeep Kumar Mallick
- School of Computer Engineering, Campus 15, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India
| | | | - Sandeep Kumar Panda
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha 751024, India.
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Jia R, Shao S, Zhang P, Yuan Y, Rong W, An Z, Lv S, Feng Y, Liu N, Feng Q, Wang Y, Li Q. PRM1201 effectively inhibits colorectal cancer metastasis via shaping gut microbiota and short- chain fatty acids. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155795. [PMID: 38878524 DOI: 10.1016/j.phymed.2024.155795] [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: 12/03/2023] [Revised: 05/28/2024] [Accepted: 06/02/2024] [Indexed: 08/21/2024]
Abstract
BACKGROUND PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined. HYPOTHESIS Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT. METHODS To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201. RESULTS Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed. CONCLUSION In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.
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Affiliation(s)
- Ru Jia
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Shiyun Shao
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Pingping Zhang
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yuan Yuan
- School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wenqing Rong
- Department of Medical Oncology, Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
| | - Ziming An
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai 201203, China
| | - Sheng Lv
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai 201203, China
| | - Yuanyuan Feng
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ningning Liu
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Qin Feng
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai 201203, China; Central Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai 201203, China.
| | - Yan Wang
- Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Qi Li
- Department of Chinese Medicine & Integrative Medicine, Shanghai Geriatric Medical Center, Zhongshan Hospital, Fudan University, 2560 Chunshen Road, Shanghai 201104, China.
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Meng EX, Verne GN, Zhou Q. Macrophages and Gut Barrier Function: Guardians of Gastrointestinal Health in Post-Inflammatory and Post-Infection Responses. Int J Mol Sci 2024; 25:9422. [PMID: 39273369 PMCID: PMC11395020 DOI: 10.3390/ijms25179422] [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: 07/31/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/15/2024] Open
Abstract
The gut barrier is essential for protection against pathogens and maintaining homeostasis. Macrophages are key players in the immune system, are indispensable for intestinal health, and contribute to immune defense and repair mechanisms. Understanding the multifaceted roles of macrophages can provide critical insights into maintaining and restoring gastrointestinal (GI) health. This review explores the essential role of macrophages in maintaining the gut barrier function and their contribution to post-inflammatory and post-infectious responses in the gut. Macrophages significantly contribute to gut barrier integrity through epithelial repair, immune modulation, and interactions with gut microbiota. They demonstrate active plasticity by switching phenotypes to resolve inflammation, facilitate tissue repair, and regulate microbial populations following an infection or inflammation. In addition, tissue-resident (M2) and infiltration (M1) macrophages convert to each other in gut problems such as IBS and IBD via major signaling pathways mediated by NF-κB, JAK/STAT, PI3K/AKT, MAPK, Toll-like receptors, and specific microRNAs such as miR-155, miR-29, miR-146a, and miR-199, which may be good targets for new therapeutic approaches. Future research should focus on elucidating the detailed molecular mechanisms and developing personalized therapeutic approaches to fully harness the potential of macrophages to maintain and restore intestinal permeability and gut health.
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Affiliation(s)
| | - George Nicholas Verne
- College of Medicine, University of Tennessee, Memphis, TN 38103, USA
- Lt. Col. Luke Weathers, Jr. VA Medical Center, Memphis, TN 38105, USA
| | - Qiqi Zhou
- College of Medicine, University of Tennessee, Memphis, TN 38103, USA
- Lt. Col. Luke Weathers, Jr. VA Medical Center, Memphis, TN 38105, USA
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Cheng W, Zhu N, Wang J, Yang R. A role of gut microbiota metabolites in HLA-E and NKG2 blockage immunotherapy against tumors: new insights for clinical application. Front Immunol 2024; 15:1331518. [PMID: 39229258 PMCID: PMC11368731 DOI: 10.3389/fimmu.2024.1331518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 07/16/2024] [Indexed: 09/05/2024] Open
Abstract
One of major breakthroughs in immunotherapy against tumor is from blocking immune checkpoint molecules on tumor and reactive T cells. The development of CTLA-4 and PD-1 blockage antibodies has triggered to search for additional effective therapeutic strategies. This causes recent findings that blocking the interaction of checkpoint molecule NKG2A in NK and CD8 T cells with HLA-E in tumors is effective in defensing tumors. Interestingly, gut microbiota also affects this immune checkpoint immunotherapy against tumor. Gut microbiota such as bacteria can contribute to the regulation of host immune response and homeostasis. They not only promote the differentiation and function of immunosuppressive cells but also the inflammatory cells through the metabolites such as tryptophan (Trp) and bile acid (BA) metabolites as well as short chain fatty acids (SCFAs). These gut microbiota metabolites (GMMs) educated immune cells can affect the differentiation and function of effective CD8 and NK cells. Notably, these metabolites also directly affect the activity of CD8 and NK cells. Furthermore, the expression of CD94/NKG2A in the immune cells and/or their ligand HLA-E in the tumor cells is also regulated by gut microbiota associated immune factors. These findings offer new insights for the clinical application of gut microbiota in precise and/or personalized treatments of tumors. In this review, we will discuss the impacts of GMMs and GMM educated immune cells on the activity of effective CD8 and NK cells and the expression of CD94/NKG2A in immune cells and/or their ligand HLA-E in tumor cells.
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Affiliation(s)
- Wenyue Cheng
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
| | - Ningning Zhu
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
| | - Juanjuan Wang
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
| | - Rongcun Yang
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
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Zhao Q, Su X, Xue J, Liu Y, Zhu J, Cai X, Qin S. First-line treatment with KN046, chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma: an open-label, dose escalation, and dose expansion phase Ib trial. Cancer Immunol Immunother 2024; 73:194. [PMID: 39105827 PMCID: PMC11303366 DOI: 10.1007/s00262-024-03769-4] [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: 03/13/2024] [Accepted: 06/25/2024] [Indexed: 08/07/2024]
Abstract
There is growing evidence to suggest that radiotherapy might enhance the efficacy of immunotherapy. This study aimed to assess the possibility of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, combined with chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma (ESCC). In this open-label, phase Ib trial, patients with advanced ESCC were administered chemotherapy with palliative radiotherapy, and KN046 in the predefined escalation dosages of 1, 3, or 5 mg/kg (every 3 weeks during chemotherapy cycles and every 2 weeks during KN046 maintenance). The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135-175 mg/m2 ivgtt., d1). Radiotherapy specifics, including site, timing, dose, and fragmentation pattern, were at the investigator's discretion. The primary outcome was dose-limiting toxicity (DLT). From May 2019 to April 2021, 25 patients were enrolled across the dosage groups: 3 in 1 mg/kg, 12 in 3 mg/kg, and 10 in 5 mg/kg. No DLT was observed during the dose escalation. The objective response rate was 41.7% (95%CI 22.1-63.4), while the disease control rate was 87.5% (95%CI 67.6-97.3). At a median follow-up of 11.8 months, the median progression-free survival was 7.8 months (95%CI 5.2-9.7) and median overall survival was 15.9 months (95%CI 8.4-NE). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients.
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Affiliation(s)
- Qi Zhao
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Xi Su
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Jiao Xue
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Yandong Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Jiaxing Zhu
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China
| | - Xuwei Cai
- Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
| | - Songbing Qin
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China.
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Mann ER, Lam YK, Uhlig HH. Short-chain fatty acids: linking diet, the microbiome and immunity. Nat Rev Immunol 2024; 24:577-595. [PMID: 38565643 DOI: 10.1038/s41577-024-01014-8] [Citation(s) in RCA: 231] [Impact Index Per Article: 231.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2024] [Indexed: 04/04/2024]
Abstract
The short-chain fatty acids (SCFAs) butyrate, propionate and acetate are microbial metabolites and their availability in the gut and other organs is determined by environmental factors, such as diet and use of antibiotics, that shape the diversity and metabolism of the microbiota. SCFAs regulate epithelial barrier function as well as mucosal and systemic immunity via evolutionary conserved processes that involve G protein-coupled receptor signalling or histone deacetylase activity. Indicatively, the anti-inflammatory role of butyrate is mediated through direct effects on the differentiation of intestinal epithelial cells, phagocytes, B cells and plasma cells, and regulatory and effector T cells. Intestinally derived SCFAs also directly and indirectly affect immunity at extra-intestinal sites, such as the liver, the lungs, the reproductive tract and the brain, and have been implicated in a range of disorders, including infections, intestinal inflammation, autoimmunity, food allergies, asthma and responses to cancer therapies. An ecological understanding of microbial communities and their interrelated metabolic states, as well as the engineering of butyrogenic bacteria may support SCFA-focused interventions for the prevention and treatment of immune-mediated diseases.
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Affiliation(s)
- Elizabeth R Mann
- Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Ying Ka Lam
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Holm H Uhlig
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
- Department of Paediatrics, University of Oxford, Oxford, UK.
- Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
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Stringer AM, Hargreaves BM, Mendes RA, Blijlevens NMA, Bruno JS, Joyce P, Kamath S, Laheij AMGA, Ottaviani G, Secombe KR, Tonkaboni A, Zadik Y, Bossi P, Wardill HR. Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework. Support Care Cancer 2024; 32:558. [PMID: 39080025 PMCID: PMC11289053 DOI: 10.1007/s00520-024-08752-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 07/19/2024] [Indexed: 08/02/2024]
Abstract
Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota's contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.
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Affiliation(s)
- Andrea M Stringer
- Clinical and Health Sciences, University of South Australia, Adelaide, 5000, Australia
| | - Benjamin M Hargreaves
- Clinical and Health Sciences, University of South Australia, Adelaide, 5000, Australia
| | - Rui Amaral Mendes
- Faculty of Medicine, University of Porto/CINTESIS@RISE, Porto, Portugal
- Department of Oral and Maxillofacial Medicine and Diagnostic Sciences, Case Western Reserve University, Cleveland, OH, 44106-7401, USA
| | - Nicole M A Blijlevens
- Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Julia S Bruno
- Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil
| | - Paul Joyce
- Centre for Pharmaceutical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, 5000, Australia
| | - Srinivas Kamath
- Centre for Pharmaceutical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, 5000, Australia
| | - Alexa M G A Laheij
- Department of Oral Medicine, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, The Netherlands
- Department of Oral and Maxillofacial Surgery, UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Giulia Ottaviani
- Department of Surgical, Medical and Health Sciences, University of Trieste, Trieste, Italy
| | - Kate R Secombe
- The School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, 5005, Australia
| | - Arghavan Tonkaboni
- Department of Oral Medicine, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Yehuda Zadik
- Department of Military Medicine and "Tzameret", Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- Department of Oral Medicine, Sedation and Imaging, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Paolo Bossi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy
- IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - Hannah R Wardill
- The School of Biomedicine, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, 5005, Australia.
- Supportive Oncology Research Group, Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Level 5S, Adelaide, 5000, Australia.
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41
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Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci 2024; 25:8250. [PMID: 39125822 PMCID: PMC11311432 DOI: 10.3390/ijms25158250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/19/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
The intricate relationship between the gastrointestinal (GI) microbiome and the progression of chronic non-communicable diseases underscores the significance of developing strategies to modulate the GI microbiota for promoting human health. The administration of probiotics and prebiotics represents a good strategy that enhances the population of beneficial bacteria in the intestinal lumen post-consumption, which has a positive impact on human health. In addition, dietary fibers serve as a significant energy source for bacteria inhabiting the cecum and colon. Research articles and reviews sourced from various global databases were systematically analyzed using specific phrases and keywords to investigate these relationships. There is a clear association between dietary fiber intake and improved colon function, gut motility, and reduced colorectal cancer (CRC) risk. Moreover, the state of health is reflected in the reciprocal and bidirectional relationships among food, dietary antioxidants, inflammation, and body composition. They are known for their antioxidant properties and their ability to inhibit angiogenesis, metastasis, and cell proliferation. Additionally, they promote cell survival, modulate immune and inflammatory responses, and inactivate pro-carcinogens. These actions collectively contribute to their role in cancer prevention. In different investigations, antioxidant supplements containing vitamins have been shown to lower the risk of specific cancer types. In contrast, some evidence suggests that taking antioxidant supplements can increase the risk of developing cancer. Ultimately, collaborative efforts among immunologists, clinicians, nutritionists, and dietitians are imperative for designing well-structured nutritional trials to corroborate the clinical efficacy of dietary therapy in managing inflammation and preventing carcinogenesis. This review seeks to explore the interrelationships among dietary antioxidants, dietary fiber, and the gut microbiome, with a particular focus on their potential implications in inflammation and cancer.
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Affiliation(s)
- Camelia Munteanu
- Department of Plant Culture, Faculty of Agriculture, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania
| | - Betty Schwartz
- The Institute of Biochemistry, Food Science and Nutrition, The School of Nutritional Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel
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Lu L, Li F, Gao Y, Kang S, Li J, Guo J. Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury. Mol Med 2024; 30:105. [PMID: 39030525 PMCID: PMC11264922 DOI: 10.1186/s10020-024-00873-0] [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: 11/06/2023] [Accepted: 07/08/2024] [Indexed: 07/21/2024] Open
Abstract
Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.
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Affiliation(s)
- Lina Lu
- School of Chemical Engineering, Northwest Minzu University, No.1, Northwest New Village, Lanzhou, Gansu, 730030, China.
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, Lanzhou, Gansu, China.
- Gansu Provincial Biomass Function Composites Engineering Research Center, Lanzhou, Gansu, China.
- Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in, University of Gansu Province, Lanzhou, Gansu, China.
| | - Fengxiao Li
- Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, China
| | | | - Shuhe Kang
- School of Chemical Engineering, Northwest Minzu University, No.1, Northwest New Village, Lanzhou, Gansu, 730030, China
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, Lanzhou, Gansu, China
- Gansu Provincial Biomass Function Composites Engineering Research Center, Lanzhou, Gansu, China
- Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in, University of Gansu Province, Lanzhou, Gansu, China
| | - Jia Li
- School of Chemical Engineering, Northwest Minzu University, No.1, Northwest New Village, Lanzhou, Gansu, 730030, China
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, Lanzhou, Gansu, China
- Gansu Provincial Biomass Function Composites Engineering Research Center, Lanzhou, Gansu, China
- Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in, University of Gansu Province, Lanzhou, Gansu, China
| | - Jinwang Guo
- School of Chemical Engineering, Northwest Minzu University, No.1, Northwest New Village, Lanzhou, Gansu, 730030, China
- Key Laboratory of Environment-Friendly Composite Materials of the State Ethnic Affairs Commission, Lanzhou, Gansu, China
- Gansu Provincial Biomass Function Composites Engineering Research Center, Lanzhou, Gansu, China
- Key Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in, University of Gansu Province, Lanzhou, Gansu, China
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Alshehri AM, Wilson OC. Biomimetic Hydrogel Strategies for Cancer Therapy. Gels 2024; 10:437. [PMID: 39057460 PMCID: PMC11275631 DOI: 10.3390/gels10070437] [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: 05/27/2024] [Revised: 06/18/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer.
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Affiliation(s)
- Awatef M. Alshehri
- Department of Biomedical Engineering, The Catholic University of America, Washington, DC 20064, USA
- Department of Nanomedicine, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdelaziz University for Health Sciences (KSAU-HS), Ministry of National Guard-Health Affairs (MNGHA), Riyadh 11426, Saudi Arabia;
| | - Otto C. Wilson
- Department of Biomedical Engineering, The Catholic University of America, Washington, DC 20064, USA
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Cheng W, Li F, Yang R. The Roles of Gut Microbiota Metabolites in the Occurrence and Development of Colorectal Cancer: Multiple Insights for Potential Clinical Applications. GASTRO HEP ADVANCES 2024; 3:855-870. [PMID: 39280926 PMCID: PMC11401567 DOI: 10.1016/j.gastha.2024.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 05/21/2024] [Indexed: 09/18/2024]
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. The occurrence and development of CRC are related to multiple risk factors such as gut microbiota. Indeed, gut microbiota plays an important role in the different phases of colorectal cancers (CRCs) from oncogenesis to metastasis. Some specific bacteria such as Fusobacterium nucleatum (F. nucleatum) associated with CRCs have been found. However, recently identified bile acid and tryptophan metabolites as well as short chain fatty acids (SCFAs), which are derived from gut microbiota, can also exert effects on the CRCs such as that SCFAs directly inhibit CRC growth. Importantly these metabolites also modulate immune responses to affect CRCs. They not only act as tumor inhibiting factor(s) but also promotor(s) in the occurrence, development, and metastasis of CRCs. While gut microbiota metabolites (GMMs) inhibit immunity against CRCs, some of them also improve immune responses to CRCs. Notably, GMMs also potentially affect the shaping of immune-privileged metastatic niches through direct roles or immune cells such as macrophages and myeloid-derived suppressive cells. These findings offer new insights for clinical application of gut microbiota in precise and personalized treatments of CRCs. Here, we will mainly discuss direct and indirect (via immune cells) effects of GMMs, especially SCFAs, bile acid and tryptophan metabolites on the occurrence, development and metastasis of CRCs.
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Affiliation(s)
- Wenyue Cheng
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
| | - Fan Li
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
| | - Rongcun Yang
- Translational Medicine Institute, Affiliated Tianjin Union Medical Center of Nankai University, Nankai University, Tianjin, China
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, China
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China
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Davoutis E, Gkiafi Z, Lykoudis PM. Bringing gut microbiota into the spotlight of clinical research and medical practice. World J Clin Cases 2024; 12:2293-2300. [PMID: 38765739 PMCID: PMC11099419 DOI: 10.12998/wjcc.v12.i14.2293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/30/2024] [Accepted: 04/07/2024] [Indexed: 04/29/2024] Open
Abstract
Despite the increasing scientific interest and expanding role of gut microbiota (GM) in human health, it is rarely reported in case reports and deployed in clinical practice. Proteins and metabolites produced by microbiota contribute to immune system development, energy homeostasis and digestion. Exo- and endogenous factors can alter its composition. Disturbance of microbiota, also known as dysbiosis, is associated with various pathological conditions. Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool. GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections. Additionally, it can influence response to treatments, including those for cancers, by altering drug bioavailability. A thorough understanding of its function has permitted significant development in therapeutics, such as probiotics and fecal transplantation. Hence, GM should be considered as a ground-breaking biological parameter, and it is advisable to be investigated and reported in literature in a more consistent and systematic way.
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Affiliation(s)
- Efstathia Davoutis
- School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Zoi Gkiafi
- School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Panagis M Lykoudis
- School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
- Division of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom
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Wasiak J, Głowacka P, Pudlarz A, Pieczonka AM, Dzitko K, Szemraj J, Witusik-Perkowska M. Lactic Acid Bacteria-Derived Postbiotics as Adjunctive Agents in Breast Cancer Treatment to Boost the Antineoplastic Effect of a Conventional Therapeutic Comprising Tamoxifen and a New Drug Candidate: An Aziridine-Hydrazide Hydrazone Derivative. Molecules 2024; 29:2292. [PMID: 38792153 PMCID: PMC11124249 DOI: 10.3390/molecules29102292] [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: 02/19/2024] [Revised: 04/24/2024] [Accepted: 04/30/2024] [Indexed: 05/26/2024] Open
Abstract
Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine-hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.
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Affiliation(s)
- Joanna Wasiak
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, Poland; (J.W.); (P.G.); (A.P.); (J.S.)
| | - Pola Głowacka
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, Poland; (J.W.); (P.G.); (A.P.); (J.S.)
| | - Agnieszka Pudlarz
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, Poland; (J.W.); (P.G.); (A.P.); (J.S.)
| | - Adam M. Pieczonka
- Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12 Str., 91-403 Lodz, Poland;
| | - Katarzyna Dzitko
- Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16 Str., 90-237 Lodz, Poland;
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, Poland; (J.W.); (P.G.); (A.P.); (J.S.)
| | - Monika Witusik-Perkowska
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, Poland; (J.W.); (P.G.); (A.P.); (J.S.)
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Huang C, Li X, Li H, Chen R, Li Z, Li D, Xu X, Zhang G, Qin L, Li B, Chu XM. Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions. J Transl Med 2024; 22:433. [PMID: 38720361 PMCID: PMC11077873 DOI: 10.1186/s12967-024-05232-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 04/23/2024] [Indexed: 05/12/2024] Open
Abstract
Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.
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Affiliation(s)
- Chao Huang
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Xiaoxia Li
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, No. 308 Ningxia Road, Qingdao, Shandong, 266000, China
| | - Hanqing Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, China
| | - Ruolan Chen
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Zhaoqing Li
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Daisong Li
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Xiaojian Xu
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Guoliang Zhang
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Luning Qin
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China
| | - Bing Li
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, No. 308 Ningxia Road, Qingdao, Shandong, 266000, China.
- Department of Dermatology, The Affiliated Haici Hospital of Qingdao University, Qingdao, 266033, China.
| | - Xian-Ming Chu
- Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao, Shandong, 266100, China.
- The Affiliated Cardiovascular Hospital of Qingdao University, No. 5 Zhiquan Road, Qingdao, 266071, China.
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Profir M, Roşu OA, Creţoiu SM, Gaspar BS. Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers. Microorganisms 2024; 12:955. [PMID: 38792785 PMCID: PMC11124004 DOI: 10.3390/microorganisms12050955] [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: 03/11/2024] [Revised: 04/25/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this "unseen organ"-the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers.
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Affiliation(s)
- Monica Profir
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania; (M.P.); (O.A.R.)
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Oana Alexandra Roşu
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania; (M.P.); (O.A.R.)
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Bogdan Severus Gaspar
- Surgery Clinic, Emergency Clinical Hospital of Bucharest, 014461 Bucharest, Romania;
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
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Deng Y, Hou X, Wang H, Du H, Liu Y. Influence of Gut Microbiota-Mediated Immune Regulation on Response to Chemotherapy. Pharmaceuticals (Basel) 2024; 17:604. [PMID: 38794174 PMCID: PMC11123941 DOI: 10.3390/ph17050604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
The involvement of the gut microbiota in anti-cancer treatment has gained increasing attention. Alterations to the structure and function of the gut bacteria are important factors in the development of cancer as well as the efficacy of chemotherapy. Recent studies have confirmed that the gut microbiota and related metabolites influence the pharmacological activity of chemotherapeutic agents through interactions with the immune system. This review aims to summarize the current knowledge of how malignant tumor and chemotherapy affect the gut microbiota, how the gut microbiota regulates host immune response, and how interactions between the gut microbiota and host immune response influence the efficacy of chemotherapy. Recent advances in strategies for increasing the efficiency of chemotherapy based on the gut microbiota are also described. Deciphering the complex homeostasis maintained by the gut microbiota and host immunity provides a solid scientific basis for bacterial intervention in chemotherapy.
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Affiliation(s)
- Yufei Deng
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
| | - Xiaoying Hou
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan 430056, China
| | - Haiping Wang
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan 430056, China
| | - Hongzhi Du
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Yuchen Liu
- Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China; (Y.D.); (X.H.); (H.W.)
- Cancer Institute, School of Medicine, Jianghan University, Wuhan 430056, China
- Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan 430056, China
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Mahdi T, Desmons A, Krasniqi P, Lacorte JM, Kapel N, Lamazière A, Fourati S, Eguether T. Effect of Stool Sampling on a Routine Clinical Method for the Quantification of Six Short Chain Fatty Acids in Stool Using Gas Chromatography-Mass Spectrometry. Microorganisms 2024; 12:828. [PMID: 38674773 PMCID: PMC11052040 DOI: 10.3390/microorganisms12040828] [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: 01/31/2024] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Short chain fatty acids (SCFAs) are primarily produced in the caecum and proximal colon via the bacterial fermentation of undigested carbohydrates that have avoided digestion in the small intestine. Increasing evidence supports the critical role that SCFAs play in health and homeostasis. Microbial SCFAs, namely butyric acid, serve as a principal energy source for colonocytes, and their production is essential for gut integrity. A direct link between SCFAs and some human pathological conditions, such as inflammatory bowel disease, irritable bowel syndrome, diarrhea, and cancer, has been proposed. The direct measurement of SCFAs in feces provides a non-invasive approach to demonstrating connections between SCFAs, microbiota, and metabolic diseases to estimate their potential applicability as meaningful biomarkers of intestinal health. This study aimed to adapt a robust analytical method (liquid-liquid extraction, followed by isobutyl chloroformate derivatization and GC-MS analysis), with comparable performances to methods from the literature, and to use this tool to tackle the question of pre-analytical conditions, namely stool processing. We focused on the methodology of managing stool samples before the analysis (fresh stool or dilution in either ethanol/methanol, lyophilized stool, or RNAlater®), as this is a significant issue to consider for standardizing results between clinical laboratories. The objective was to standardize methods for future applications as diagnostic tools. In this paper, we propose a validated GC-MS method for SCFA quantification in stool samples, including pre- and post-analytical comparison studies that could be easily used for clinical laboratory purposes. Our results show that using lyophilization as a stool-processing method would be the best method to achieve this goal.
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Affiliation(s)
- Tarek Mahdi
- Hôpital Pitié Salpêtrière-Charles Foix, AP-HP, Service de Biochimie Endocrinienne et Oncologique, 75000 Paris, France
- Sorbonne Université, Inserm, UMR_S 1166, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, 75000 Paris, France
| | - Aurore Desmons
- Centre de Recherche Saint-Antoine, Sorbonne Université, INSERM, AP-HP, Département Metomics, Hôpital Saint Antoine, 75000 Paris, France
| | - Pranvera Krasniqi
- Centre de Recherche Saint-Antoine, Sorbonne Université, INSERM, AP-HP, Département Metomics, Hôpital Saint Antoine, 75000 Paris, France
| | - Jean-Marc Lacorte
- Hôpital Pitié Salpêtrière-Charles Foix, AP-HP, Service de Biochimie Endocrinienne et Oncologique, 75000 Paris, France
- Sorbonne Université, Inserm, UMR_S 1166, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, 75000 Paris, France
| | - Nathalie Kapel
- Hôpital Pitié Salpêtrière-Charles Foix, AP-HP, Service de Coprologie Fonctionnelle, 75000 Paris, France
- Université Paris Cité, Inserm, UMR_S 1139, 75000 Paris, France
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, 75000 Paris, France
| | - Antonin Lamazière
- Centre de Recherche Saint-Antoine, Sorbonne Université, INSERM, AP-HP, Département Metomics, Hôpital Saint Antoine, 75000 Paris, France
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, 75000 Paris, France
| | - Salma Fourati
- Hôpital Pitié Salpêtrière-Charles Foix, AP-HP, Service de Biochimie Endocrinienne et Oncologique, 75000 Paris, France
- Sorbonne Université, Inserm, UMR_S 1166, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, 75000 Paris, France
| | - Thibaut Eguether
- Centre de Recherche Saint-Antoine, Sorbonne Université, INSERM, AP-HP, Département Metomics, Hôpital Saint Antoine, 75000 Paris, France
- Paris Center for Microbiome Medicine, Federation Hospitalo-Universitaire, 75000 Paris, France
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