{"title":"评估益生菌对癌症免疫治疗有效性和抗生素介导耐药的影响：一项系统综述和荟萃分析。","authors":"Shuya Zhao, Zian Lu, Fangmin Zhao, Shihuan Tang, Lishan Zhang, Cuiling Feng","doi":"10.3389/fimmu.2025.1538969","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Probiotics have been demonstrated to exert a potential clinical enhancing effect in cancer patients receiving immune checkpoint inhibitors (ICIs), while antibiotics exert a detrimental impact. Prior meta-analysis papers have substantial limitations and are devoid of recent published studies. Therefore, this study aimed to perform an updated meta-analysis and, for the first time, assess whether probiotics can restore the damage of antibiotics to immunotherapy.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in three English databases and three Chinese databases with a cutoff date of August 11, 2024. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) or the Revised Cochrane risk-of-bias tool (RoB 2). Engauge Digitizer v12.1 was employed to extract hazard ratios (HRs) with 95% confidence interval (CI) for survival outcomes when these data were not explicitly provided in the manuscripts. Meta-analysis was conducted using Stata 14 software.</p><p><strong>Results: </strong>The study sample comprised eight retrospective and four prospective studies, involving a total of 3,142 participants. The findings indicate that probiotics significantly prolong the overall survival (OS) (I<sup>2</sup> = 31.2%; HR=0.58, 95% CI: 0.46-0.73, p < 0.001) and progression-free survival (PFS) (I<sup>2</sup> = 65.2%; HR=0.66, 95% CI: 0.54-0.81, p < 0.001) in cancer patients receiving ICIs, enhance the objective response rate (ORR) (I<sup>2</sup> = 33.5%; OR=1.75, 95% CI: 1.27-2.40, p = 0.001) and disease control rate (DCR) (I<sup>2</sup> = 50.0%; OR=1.93, 95% CI: 1.11-3.35, p = 0.002). For non-small cell lung cancer (NSCLC) patients exposed to antibiotics, the use of probiotics was associated with superior OS (I<sup>2</sup> = 0.0%; HR=0.45, 95% CI: 0.34-0.59, p < 0.001) and PFS (I<sup>2</sup> = 0.0%; HR=0.48, 95% CI: 0.38-0.62, p < 0.001) when compared to non-users. Subgroup differences were observed regarding the cancer type (P=0.006) and ethnic backgrounds (P=0.011) in OS.</p><p><strong>Conclusions: </strong>The meta-analysis findings suggest that probiotics can effectively extend the survival of cancer treated with ICIs. In NSCLC, probiotics appear to mitigate the negative impact of antibiotics on immunotherapy effectiveness, which has profound clinical significance. Nevertheless, additional large-scale, high-quality randomized controlled trials are necessary to further validate these findings.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=579047, identifier CRD42024579047.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1538969"},"PeriodicalIF":5.7000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968366/pdf/","citationCount":"0","resultStr":"{\"title\":\"Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis.\",\"authors\":\"Shuya Zhao, Zian Lu, Fangmin Zhao, Shihuan Tang, Lishan Zhang, Cuiling Feng\",\"doi\":\"10.3389/fimmu.2025.1538969\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Probiotics have been demonstrated to exert a potential clinical enhancing effect in cancer patients receiving immune checkpoint inhibitors (ICIs), while antibiotics exert a detrimental impact. Prior meta-analysis papers have substantial limitations and are devoid of recent published studies. Therefore, this study aimed to perform an updated meta-analysis and, for the first time, assess whether probiotics can restore the damage of antibiotics to immunotherapy.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in three English databases and three Chinese databases with a cutoff date of August 11, 2024. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) or the Revised Cochrane risk-of-bias tool (RoB 2). Engauge Digitizer v12.1 was employed to extract hazard ratios (HRs) with 95% confidence interval (CI) for survival outcomes when these data were not explicitly provided in the manuscripts. Meta-analysis was conducted using Stata 14 software.</p><p><strong>Results: </strong>The study sample comprised eight retrospective and four prospective studies, involving a total of 3,142 participants. The findings indicate that probiotics significantly prolong the overall survival (OS) (I<sup>2</sup> = 31.2%; HR=0.58, 95% CI: 0.46-0.73, p < 0.001) and progression-free survival (PFS) (I<sup>2</sup> = 65.2%; HR=0.66, 95% CI: 0.54-0.81, p < 0.001) in cancer patients receiving ICIs, enhance the objective response rate (ORR) (I<sup>2</sup> = 33.5%; OR=1.75, 95% CI: 1.27-2.40, p = 0.001) and disease control rate (DCR) (I<sup>2</sup> = 50.0%; OR=1.93, 95% CI: 1.11-3.35, p = 0.002). For non-small cell lung cancer (NSCLC) patients exposed to antibiotics, the use of probiotics was associated with superior OS (I<sup>2</sup> = 0.0%; HR=0.45, 95% CI: 0.34-0.59, p < 0.001) and PFS (I<sup>2</sup> = 0.0%; HR=0.48, 95% CI: 0.38-0.62, p < 0.001) when compared to non-users. 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引用次数: 0
摘要
背景：益生菌已被证明对接受免疫检查点抑制剂（ICIs）治疗的癌症患者具有潜在的临床增强作用，而抗生素则具有不利影响。先前的元分析论文有很大的局限性，并且缺乏最近发表的研究。因此，本研究旨在进行一项更新的荟萃分析，并首次评估益生菌是否可以恢复抗生素对免疫治疗的损害。方法：对3个英文数据库和3个中文数据库进行综合文献检索，截止日期为2024年8月11日。使用纽卡斯尔-渥太华质量评估量表（NOS）或修订后的Cochrane风险偏倚工具（RoB 2）对研究的方法学质量进行评估。当手稿中没有明确提供这些数据时，使用Engauge Digitizer v12.1提取生存结果的风险比（hr）和95%置信区间（CI）。采用Stata 14软件进行meta分析。结果：研究样本包括8项回顾性研究和4项前瞻性研究，共涉及3142名参与者。结果表明，益生菌显著延长了总生存期（OS） (I2 = 31.2%；HR=0.58, 95% CI: 0.46-0.73, p < 0.001)和无进展生存期（PFS） (I2 = 65.2%；HR=0.66, 95% CI: 0.54-0.81, p < 0.001)，提高客观缓解率（ORR） (I2 = 33.5%；OR=1.75, 95% CI: 1.27-2.40, p = 0.001)和疾病控制率（DCR） (I2 = 50.0%；OR=1.93, 95% CI: 1.11-3.35, p = 0.002)。对于暴露于抗生素的非小细胞肺癌（NSCLC）患者，益生菌的使用与更好的OS相关(I2 = 0.0%；HR=0.45, 95% CI: 0.34-0.59, p < 0.001)和PFS (I2 = 0.0%；HR=0.48, 95% CI: 0.38-0.62, p < 0.001)。在肿瘤类型（P=0.006）和种族背景（P=0.011）方面存在亚组差异。结论：荟萃分析结果表明，益生菌可以有效延长接受ICIs治疗的癌症患者的生存期。在非小细胞肺癌中，益生菌似乎可以减轻抗生素对免疫治疗效果的负面影响，具有深远的临床意义。然而，需要更多的大规模、高质量的随机对照试验来进一步验证这些发现。系统综述注册：https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=579047，标识符CRD42024579047。
Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: a systematic review and meta-analysis.
Background: Probiotics have been demonstrated to exert a potential clinical enhancing effect in cancer patients receiving immune checkpoint inhibitors (ICIs), while antibiotics exert a detrimental impact. Prior meta-analysis papers have substantial limitations and are devoid of recent published studies. Therefore, this study aimed to perform an updated meta-analysis and, for the first time, assess whether probiotics can restore the damage of antibiotics to immunotherapy.
Methods: A comprehensive literature search was conducted in three English databases and three Chinese databases with a cutoff date of August 11, 2024. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) or the Revised Cochrane risk-of-bias tool (RoB 2). Engauge Digitizer v12.1 was employed to extract hazard ratios (HRs) with 95% confidence interval (CI) for survival outcomes when these data were not explicitly provided in the manuscripts. Meta-analysis was conducted using Stata 14 software.
Results: The study sample comprised eight retrospective and four prospective studies, involving a total of 3,142 participants. The findings indicate that probiotics significantly prolong the overall survival (OS) (I2 = 31.2%; HR=0.58, 95% CI: 0.46-0.73, p < 0.001) and progression-free survival (PFS) (I2 = 65.2%; HR=0.66, 95% CI: 0.54-0.81, p < 0.001) in cancer patients receiving ICIs, enhance the objective response rate (ORR) (I2 = 33.5%; OR=1.75, 95% CI: 1.27-2.40, p = 0.001) and disease control rate (DCR) (I2 = 50.0%; OR=1.93, 95% CI: 1.11-3.35, p = 0.002). For non-small cell lung cancer (NSCLC) patients exposed to antibiotics, the use of probiotics was associated with superior OS (I2 = 0.0%; HR=0.45, 95% CI: 0.34-0.59, p < 0.001) and PFS (I2 = 0.0%; HR=0.48, 95% CI: 0.38-0.62, p < 0.001) when compared to non-users. Subgroup differences were observed regarding the cancer type (P=0.006) and ethnic backgrounds (P=0.011) in OS.
Conclusions: The meta-analysis findings suggest that probiotics can effectively extend the survival of cancer treated with ICIs. In NSCLC, probiotics appear to mitigate the negative impact of antibiotics on immunotherapy effectiveness, which has profound clinical significance. Nevertheless, additional large-scale, high-quality randomized controlled trials are necessary to further validate these findings.
期刊介绍：
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. 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.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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