{"title":"粪便菌群移植通过调节肠道菌群增强5-氟尿嘧啶治疗胰腺癌的疗效。","authors":"Rui Li, Yaoyuan Hu, Yixian Liu, Xiaodong Tan","doi":"10.3389/fmicb.2025.1548027","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options due to rapid tumor progression and poor prognosis. Fecal Microbiota Transplantation (FMT) has emerged as a promising approach to modulate gut microbiota, potentially enhancing the efficacy of conventional treatments.</p><p><strong>Objectives: </strong>This study evaluates the combined effects of FMT and 5-fluorouracil (5FU) on gut microbiota composition, pancreatic tumor growth, and systemic immune responses in a murine model.</p><p><strong>Methods: </strong>One hundred female C57BL/6 mice aged 6-8 weeks were randomly divided into five groups (<i>n</i> = 20 each): Sham, Model, FMT, 5FU, and FMT + 5FU. Pancreatic tumors were induced via orthotopic implantation of Pan02 cells. FMT was administered orally (0.2 g fecal material) three times per week, starting 2 weeks before tumor implantation. 5FU was administered intraperitoneally at 25 mg/kg body weight twice weekly, beginning one-week post-tumor implantation. Gut microbiota was analyzed via 16S rRNA gene sequencing of fecal samples after 10-week cell implantation. Tumor volumes were measured, and serum cytokine levels were assessed. Short-chain fatty acids (SCFAs) in blood and feces using gas chromatography-mass spectrometry (GC-MS).</p><p><strong>Results: </strong>The FMT + 5FU group exhibited the smallest average tumor volume, significantly smaller than the Model (<i>p</i> < 0.0001) and 5FU groups (<i>p</i> = 0.005). FMT alone reduced tumor volume compared to the Model group (<i>p</i> < 0.0001). Gut microbiota analysis revealed increased <i>α</i> diversity in the FMT group compared to the Model group (<i>p</i> < 0.0001). The FMT + 5FU group showed a significant reduction in cytokine levels, including TNF-<i>α</i> (<i>p</i> = 0.0001) and IL-6 (<i>p</i> = 0.012) and increased IL-10 level (<i>p</i> < 0.001), compared to the Model group. Plasma and fecal SCFA concentrations were significantly higher in both FMT and FMT + 5FU groups relative to the Model group (<i>p</i> < 0.001). Additionally, the FMT + 5FU group had the highest survival rate (50%) after 10-week cell implantation, compared to the Model group (15%).</p><p><strong>Conclusion: </strong>FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1548027"},"PeriodicalIF":4.0000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507756/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fecal microbiota transplantation augments 5-fluorouracil efficacy in pancreatic cancer via gut microbiota modulation.\",\"authors\":\"Rui Li, Yaoyuan Hu, Yixian Liu, Xiaodong Tan\",\"doi\":\"10.3389/fmicb.2025.1548027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options due to rapid tumor progression and poor prognosis. Fecal Microbiota Transplantation (FMT) has emerged as a promising approach to modulate gut microbiota, potentially enhancing the efficacy of conventional treatments.</p><p><strong>Objectives: </strong>This study evaluates the combined effects of FMT and 5-fluorouracil (5FU) on gut microbiota composition, pancreatic tumor growth, and systemic immune responses in a murine model.</p><p><strong>Methods: </strong>One hundred female C57BL/6 mice aged 6-8 weeks were randomly divided into five groups (<i>n</i> = 20 each): Sham, Model, FMT, 5FU, and FMT + 5FU. Pancreatic tumors were induced via orthotopic implantation of Pan02 cells. FMT was administered orally (0.2 g fecal material) three times per week, starting 2 weeks before tumor implantation. 5FU was administered intraperitoneally at 25 mg/kg body weight twice weekly, beginning one-week post-tumor implantation. Gut microbiota was analyzed via 16S rRNA gene sequencing of fecal samples after 10-week cell implantation. Tumor volumes were measured, and serum cytokine levels were assessed. Short-chain fatty acids (SCFAs) in blood and feces using gas chromatography-mass spectrometry (GC-MS).</p><p><strong>Results: </strong>The FMT + 5FU group exhibited the smallest average tumor volume, significantly smaller than the Model (<i>p</i> < 0.0001) and 5FU groups (<i>p</i> = 0.005). FMT alone reduced tumor volume compared to the Model group (<i>p</i> < 0.0001). Gut microbiota analysis revealed increased <i>α</i> diversity in the FMT group compared to the Model group (<i>p</i> < 0.0001). The FMT + 5FU group showed a significant reduction in cytokine levels, including TNF-<i>α</i> (<i>p</i> = 0.0001) and IL-6 (<i>p</i> = 0.012) and increased IL-10 level (<i>p</i> < 0.001), compared to the Model group. Plasma and fecal SCFA concentrations were significantly higher in both FMT and FMT + 5FU groups relative to the Model group (<i>p</i> < 0.001). Additionally, the FMT + 5FU group had the highest survival rate (50%) after 10-week cell implantation, compared to the Model group (15%).</p><p><strong>Conclusion: </strong>FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.</p>\",\"PeriodicalId\":12466,\"journal\":{\"name\":\"Frontiers in Microbiology\",\"volume\":\"16 \",\"pages\":\"1548027\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507756/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Microbiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fmicb.2025.1548027\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmicb.2025.1548027","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Fecal microbiota transplantation augments 5-fluorouracil efficacy in pancreatic cancer via gut microbiota modulation.
Background: Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options due to rapid tumor progression and poor prognosis. Fecal Microbiota Transplantation (FMT) has emerged as a promising approach to modulate gut microbiota, potentially enhancing the efficacy of conventional treatments.
Objectives: This study evaluates the combined effects of FMT and 5-fluorouracil (5FU) on gut microbiota composition, pancreatic tumor growth, and systemic immune responses in a murine model.
Methods: One hundred female C57BL/6 mice aged 6-8 weeks were randomly divided into five groups (n = 20 each): Sham, Model, FMT, 5FU, and FMT + 5FU. Pancreatic tumors were induced via orthotopic implantation of Pan02 cells. FMT was administered orally (0.2 g fecal material) three times per week, starting 2 weeks before tumor implantation. 5FU was administered intraperitoneally at 25 mg/kg body weight twice weekly, beginning one-week post-tumor implantation. Gut microbiota was analyzed via 16S rRNA gene sequencing of fecal samples after 10-week cell implantation. Tumor volumes were measured, and serum cytokine levels were assessed. Short-chain fatty acids (SCFAs) in blood and feces using gas chromatography-mass spectrometry (GC-MS).
Results: The FMT + 5FU group exhibited the smallest average tumor volume, significantly smaller than the Model (p < 0.0001) and 5FU groups (p = 0.005). FMT alone reduced tumor volume compared to the Model group (p < 0.0001). Gut microbiota analysis revealed increased α diversity in the FMT group compared to the Model group (p < 0.0001). The FMT + 5FU group showed a significant reduction in cytokine levels, including TNF-α (p = 0.0001) and IL-6 (p = 0.012) and increased IL-10 level (p < 0.001), compared to the Model group. Plasma and fecal SCFA concentrations were significantly higher in both FMT and FMT + 5FU groups relative to the Model group (p < 0.001). Additionally, the FMT + 5FU group had the highest survival rate (50%) after 10-week cell implantation, compared to the Model group (15%).
Conclusion: FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.
期刊介绍：
Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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