Meta-analysis of probiotics in the prevention and treatment of chemotherapy-induced diarrhea
-
摘要: 目的 系统评价益生菌在预防和治疗化疗性腹泻(chemotherapy-induced diarrhea，CID)中的安全性和有效性，为临床实践提供循证依据。方法 检索包括EMbase、Cochrane图书馆、PubMed、中国知网、维普数据库、中国生物医学文献数据库和万方数据库在内的电子数据库，搜索截至2023年9月31日接受益生菌治疗的CID的随机对照试验(randomized controlled trial，RCT)。使用RevMan 5.1统计软件提取数据并评估所鉴定文献的质量以进行meta分析。结果 共纳入包括1 032例患者的13项RCT。研究结果提示，止泻等常规对症疗法联合益生菌制剂可显著降低化疗期间的总腹泻率(OR=0.33，95%CI：0.21~0.51，P < 0.001)和Ⅲ~Ⅳ级腹泻率(OR=0.12，95%CI：0.04~0.39，P < 0.001)，进而提升总有效率(OR=4.26，95%CI：2.55~7.12，P < 0.001)，并缩短腹泻持续时间(MD=-1.92，95%CI：-1.96~-1.88，P < 0.001)，但在Ⅰ~Ⅱ级腹泻患者中差异无统计学意义(OR=0.73，95%CI：0.39~1.38，P=0.330)。同时，没有一项研究报告有不良反应发生。结论 预防性或同时在化疗期间应用益生菌制剂可有效防治肿瘤患者发生CID，安全性良好。Abstract: Objective To systematically evaluate the safety and efficacy of probiotics in preventing and treating chemotherapy-induced diarrhea(CID), so as to provide the evidence-based evidence for clinical practice.Methods Electronic databases, including EMbase, Cochrane Library, PubMed, CNKI, CBM, VIP and Wanfang databases, were retrieved to search for the randomized controlled trial(RCT) of CID among patients with malignant tumors treated with probiotics as of September 31, 2023. Later, the RevMan 5.1 statistical software was employed to extract data and assess the quality of the identified literature for meta-analysis.Results Thirteen RCT involving a total of 1 032 patients were included into the current meta-analysis. Results of this meta-analysis suggested that conventional symptomatic therapy combined with probiotics could significantly reduce the total diarrhea rate in tumor patients(OR=0.33, 95%CI: 0.21-0.51, P < 0.001)and grade Ⅲ-Ⅳdiarrhea(OR=0.12, 95%CI: 0.04-0.39, P < 0.001), increase the total effective rate(OR=4.26, 95%CI: 2.55-7.12, P < 0.001), and shorten the duration of diarrhea(MD=-1.92, 95%CI: -1.96--1.88, P < 0.001), with significant difference. But among patients with gradeⅠ-Ⅱ diarrhea(OR=0.73, 95%CI: 0.39-1.38, P=0.330), the difference was not statistically significant. Besides, none of the enrolled study had reported adverse reactions.Conclusion Probiotics can prevent and treat CID of tumor patients effectively during chemotherapy, with less adverse events.
-
Key words:
- probiotics /
- chemotherapy-induced diarrhea /
- gut microbiota /
- duration of diarrhea
-
-
表 1 PubMed检索策略
步骤 检索策略 #1 (((((chemotherapy)AND diarrhea))OR chemotherapy-induced diarrhea)OR CID) #2 (((((Yeast)OR Bifidobacterium)OR)OR Lactococcus)OR probiotics)OR Lactobacillus #3 (((randomized controlled trial [pt]OR controlled clinical trial [pt]OR randomized controlled trial[mh]OR double-blind method[mh]OR single-blind method[mh]OR clinical trial[pt]OR clinical trials[mh]OR(“clinical trial”)[tw]OR singl*[tw]OR doubl*[tw]OR trebl*[tw]OR tripl* [tw] AND (mask* [tw] OR blind* [tw])) OR comparative study [mh] OR evaluation studies [mh] OR follow-up studies [mh] OR prospective studies [mh] OR control* [tw] OR prospective* [tw] OR volunteer* [tw] NOT (animals [mh] NOT humans [mh]).)))NOT((systematic reviews OR meta-analysis))) NOT (((Cohort studies or case reports or Letter or Historical Article or comment).pt))) NOT (((comment OR editorial OR meta-analysis OR practice-guideline OR review OR letter OR journal correspondence))) #4 #1 and #2 and #3 注：以上显示了文献筛选过程，结合了医学主题词(MeSH)和自由词检索。 
下载: 导出CSV
表 2 纳入研究的基本信息
文献 国家 发表时间 样本量/例 化疗方案 干预措施 用药目的 结局指标 试验组 对照组 试验组 对照组 常方芝等[10] 中国 2007 21 23 胃癌：5-Fu+阿霉素+丝裂霉素；结直肠癌：FOLFIRI 奥曲肽+常规治疗+培菲康 奥曲肽+常规治疗 治疗 ① 韦惠章等[11] 中国 2017 30 30 CPT-11+5-Fu 化疗+双歧杆菌 化疗 预防 ②③④⑤ 方立萍等[12] 中国 2011 18 18 CPT-11 化疗+双歧杆菌 化疗 预防 ②③④⑤ 乐少华等[13] 中国 2011 58 58 阿糖胞苷 地衣芽孢杆菌胶囊 安慰剂 预防+治疗 ② 梁淑文等[14] 中国 2014 44 41 希罗达+奥沙利铂 常规治疗+培菲康+蒙脱石散 常规治疗+蒙脱石散 治疗 ① 姚月荣等[15] 中国 2017 63 63 化疗 洛哌丁胺+双歧杆菌 洛哌丁胺 治疗 ① 张冬梅等[16] 中国 2013 30 30 FOLFOX4 地衣芽孢杆菌胶囊+常规治疗 蒙脱石散+常规治疗 治疗 ① 周雪峰等[17] 中国 2017 45 63 化疗 蒙脱石散+常规治疗+双歧杆菌 蒙脱石散+常规治疗 治疗 ① 贺永军等[18] 中国 2014 55 53 化疗 枯草芽孢杆菌+洛哌丁胺+常规治疗 常规治疗+蒙脱石散 治疗 ① 敖苗等[19] 中国 2012 74 51 环磷酰胺 双歧杆菌 安慰剂 预防 ② 刘基巍等[20] 中国 2000 22 22 5-Fu+紫杉醇 双歧杆菌+化疗 化疗 预防 ②③④⑤ 庄贤栩等[21] 中国 2015 37 37 化疗 双歧杆菌+常规治疗 常规治疗 治疗 ①⑤ Mego等[22] 斯洛伐克 2015 23 23 CPT-11+5-Fu 双歧杆菌+乳酸杆菌 安慰剂 预防 ②③④⑤ 注：①总有效率；②总腹泻率；③Ⅰ~Ⅱ级腹泻率；④Ⅲ~Ⅳ级腹泻率；⑤腹泻持续时间。
下载: 导出CSV
-
[1] Akbarali HI, Muchhala KH, Jessup DK, et al. Chemotherapy induced gastrointestinal toxicities[J]. Adv Cancer Res, 2022, 155: 131-166.
[2] Dahlgren D, Sjoblom M, Hellstrom PM, et al. Chemotherapeutics-induced intestinal mucositis: Pathophysiology and potential treatment strategies[J]. Front Pharmacol, 2021, 12: 681417. doi: 10.3389/fphar.2021.681417
[3] NCCN. 癌症相关感染的预防和治疗指南(2022.3版)[EB/OL]. [2023-09-16].
https://nccn.medlive.cn/guide/index .[4] Nobre LMS, Fernandes C, Florencio KGD, et al. Could paraprobiotics be a safer alternative to probiotics for managing cancer chemotherapy-induced gastrointestinal toxicities?[J]. Braz J Med Biol Res, 2023, 55: e12522.
[5] Xia C, Jiang C, Li W, et al. A Phase ⅡRandomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma[J]. Front Immunol, 2021, 12: 618150. doi: 10.3389/fimmu.2021.618150
[6] Huang G, Khan R, Zheng Y, et al. Exploring the role of gut microbiota in advancing personalized medicine[J]. Front Microbiol, 2023, 14: 1274925. doi: 10.3389/fmicb.2023.1274925
[7] Freites-Martinez A, Santana N, Arias-Santiago S, et al. Using the Common Terminology Criteria for Adverse Events(CTCAE-Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies[J]. Actas Dermosifiliogr (Engl Ed), 2021, 112(1): 90-92. doi: 10.1016/j.ad.2019.05.009
[8] Cumpston MS, McKenzie JE, Welch VA, et al. Strengthening systematic reviews in public health: guidance in the Cochrane Handbook for Systematic Reviews of Interventions, 2nd edition[J]. J Public Health(Oxf), 2022, 44(4): e588-e592. doi: 10.1093/pubmed/fdac036
[9] 刘鸣. 系统评价: Meta-分析设计与实施方法[M]. 北京: 人民卫生出版社, 2023: 98-107.
[10] 常方芝, 孙方利, 马文香, 等. 消化道肿瘤化疗相关性腹泻的治疗研究[J]. 上海医药, 2007, 28(11): 523-525. doi: 10.3969/j.issn.1006-1533.2007.11.017
[11] 韦惠章, 何海滨, 麦哲林, 等. 双歧杆菌对晚期大肠癌伊立替康化疗相关性腹泻的影响研究[J]. 中国实用医药, 2017, 12(5): 125-126. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSSA201715072.htm
[12] 方立萍, 吴紫权, 宋晨, 等. 双歧杆菌活菌胶囊预防CPT-11引起的化疗相关性腹泻的疗效观察[J]. 中国微生态学杂志, 2011, 23(3): 241-242. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWS201103017.htm
[13] 乐少华, 李健. 整肠生防治儿童白血病化疗继发腹泻的临床观察[J]. 中国社区医师(医学专业), 2011, 13(17): 121-121. doi: 10.3969/j.issn.1007-614x.2011.17.119
[14] 梁淑文, 屈昌民, 王晓英, 等. 益生菌治疗结肠癌患者术后化疗相关性腹泻的效果观察[J]. 现代生物医学进展, 2014, 14(24): 4686-4688. https://www.cnki.com.cn/Article/CJFDTOTAL-SWCX201424022.htm
[15] 姚月荣, 李新宇. 益生菌治疗妇科恶性肿瘤患者化疗相关性腹泻的疗效观察[J]. 基因组学与应用生物学, 2017, 36(11): 4510-4515. https://www.cnki.com.cn/Article/CJFDTOTAL-GXNB201711018.htm
[16] 张冬梅, 陈嫒, 王蓉, 等. 益生菌治疗化疗相关性腹泻的前瞻性研究[J]. 临床消化病杂志, 2013, 25(1): 20-23. doi: 10.3870/1cxh.j.issn.1005-541X.2013.01.05
[17] 周雪峰, 何瑛, 王石健, 等. 益生菌对白血病化疗后继发腹泻患者的影响[J]. 世界华人消化杂志, 2017, 25(36): 3248-3252.
[18] 贺永军, 孙翠清, 吕芳芳. 美常安联合洛哌丁胺治疗化疗相关性腹泻临床研究[J]. 医药论坛杂志, 2014, 35(4): 116-117. https://www.cnki.com.cn/Article/CJFDTOTAL-HYYX201404062.htm
[19] 敖苗, 刘玉峰. 不同剂型益生菌预防儿童急性淋巴细胞白血病化疗所致腹泻的比较[J]. 临床儿科杂志, 2012, 30(10): 932-934. doi: 10.3969/j.issn.1000-3606.2012.10.010
[20] 刘基巍, 周涛, 张洁, 等. 双歧杆菌DM-8504活菌制剂预防化疗引起的腹泻疗效观察[J]. 中国微生态学杂志, 2000, 12(3): 57-58. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWS200003024.htm
[21] 庄贤栩, 裴仁治, 陆滢, 等. 双歧杆菌三联活菌胶囊对白血病化疗所致腹泻患者肠粘膜屏障功能的影响及疗效观察[J]. 中国医药导报, 2015, 12(3): 110-113. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY201503032.htm
[22] Mego M, Chovanec J, Vochyanova-Andrezalova I, et al. Prevention of irinotecan induced diarrhea by probiotics: A randomized double blind, placebo controlled pilot study[J]. Complement Ther Med, 2015, 23(3): 356-362. doi: 10.1016/j.ctim.2015.03.008
[23] Yeung CY, Chiang Chiau JS, Cheng ML, et al. Modulations of probiotics on gut microbiota in a 5-fluorouracil-induced mouse model of mucositis[J]. J Gastroenterol Hepatol, 2020, 35(5): 806-814.
[24] Barroso FAL, de Jesus LCL, da Silva TF, et al. Lactobacillus delbrueckii CIDCA 133 Ameliorates Chemotherapy-Induced Mucositis by Modulating Epithelial Barrier and TLR2/4/Myd88/NF-κB Signaling Pathway[J]. Front Microbiol, 2022, 13, 858036.
[25] Shen SR, Chen WJ, Chu HF, et al. Amelioration of 5-fluorouracil-induced intestinal mucositis by Streptococcus thermophilus ST4 in a mouse model. [J]. PLoS One, 2021, 16: e0253540.
[26] Jakubauskas M, Jakubauskiene L, Leber B, et al. Probiotic Supplementation Attenuates Chemotherapy-Induced Intestinal Mucositis in an Experimental Colorectal Cancer Liver Metastasis Rat Model[J]. Nutrients, 2023, 15: 1117.
-
计量
- 文章访问数: 330
- 施引文献: 0