中国抗癌协会

1. 概述

肿瘤与微生态的相互作用已成为现代医学研究的前沿领域。最新流行病学数据显示，约20%的恶性肿瘤发生发展与人体微生物组的异常定植、代谢失衡密切相关，涉及消化道肿瘤、乳腺癌、黑色素瘤等多个瘤种，特定病原体（如幽门螺杆菌、具核梭杆菌）通过慢性炎症、免疫调控等机制被确认为致癌因子。学科定义涵盖宿主-微生物相互作用对肿瘤发生、治疗响应及预后的系统性影响，研究范畴包括微生物组标志物筛查、菌群代谢产物干预、微生态重塑治疗等方向。当前焦点集中于核心致癌菌群的异质性特征、菌群干预以及微生态与免疫治疗协同作用的分子机制。在实体瘤中，原发灶与继发病灶的生物学特性差异显著，尤其对于具有高度微环境异质性的瘤种，临床管理面临巨大挑战。以消化道肿瘤为例，虽然常见亚型仅占病理分类的5%-8%，但不同菌群特征可导致治疗敏感性相差3倍以上。随着宏基因组测序、代谢组学及合成生物学技术的突破，研究发现特定共生菌能显著增强免疫治疗疗效，而致病菌过度增殖可诱导化疗耐药。当前治疗模式正从单一抗菌策略转向多维调控，包括选择性菌群移植、工程化益生菌载体、代谢酶靶向抑制等创新手段。内科治疗聚焦于菌群-药物协同增效，如粪菌移植（fecal microbiota transplantation，FMT）联合免疫检查点抑制剂可使晚期黑色素瘤客观缓解率提升至58%。放疗技术创新体现在微生物定向增敏技术，通过调控放射防护相关菌群代谢通路，使肿瘤局部控制率提高22%。微生态治疗领域迎来突破性进展：FMT已从传统艰难梭菌感染拓展至肿瘤免疫治疗增效，Ⅲ期临床试验证实标准化粪菌胶囊可使免疫治疗无应答患者的疾病控制率达到41.2%。新型微生物疗法如合成菌群联合体通过模块化设计实现特定代谢功能编程，在动物模型中成功逆转肿瘤相关免疫失衡。目前争议集中于菌群移植的长期安全性，特别是致癌代谢物（如次级胆汁酸）的跨器官迁移风险。未来需建立多组学指导的个体化微生态干预体系，期待更多开展多中心、大样本临床研究，获取更好的改善肿瘤患者微生态失衡的治疗方法和措施。

4. 本学科发展趋势与对策

4.3 未来5年发展对策

4.3.1 政策体系完善与技术准入规范

当前人体微生态与免疫调控诊疗技术的推广应用面临系统性制度瓶颈。数据显示，全国范围内仍有13个省级行政区域未将FMT技术纳入地方诊疗科目目录，技术准入的行政壁垒导致区域间发展失衡。更值得关注的是，国家层面尚未建立FMT技术操作人员的规范化培训认证体系，现有从业人员持证上岗率不足42%，严重影响技术实施的标准化进程。建议由国家卫生健康委牵头建立三级管理制度：在省级层面制定《肠道菌群移植技术临床应用实施细则》，在地市级建立技术准入评审专家库，在医疗机构层面实施主诊医师备案制。同时依托国家级继续医学教育基地，构建"理论培训-动物实验-临床观摩-独立操作"的四阶段认证体系，确保2025年前实现县域医疗机构FMT技术持证人员覆盖率突破60%。

4.3.2 诊疗路径标准化与精准分层体系

现有诊疗体系存在检测与治疗脱节的突出问题，超过75%的医疗机构尚未建立基于菌群检测的精准分层治疗方案。建议将肠道菌群宏基因组检测纳入《医疗机构临床检验项目目录》，制定《人体微生态诊疗分层技术指南》，确立以菌群α多样性指数（阈值＜3.0）、短链脂肪酸谱（乙酸/丙酸比值标准范围1.5-2.5）等12项核心指标为基准的三级诊疗体系：①轻度失调（评分＜40）采用膳食干预联合益生菌制剂；②中度紊乱（40-70分）实施功能菌定植联合FMT序贯治疗；③重度异常（＞70分）启动噬菌体-生物制剂-CGT联合治疗方案。通过建立多中心临床研究数据库，开发AI辅助决策系统（诊断符合率≥90%），实现诊疗方案的动态优化。

4.3.3 全链条质控标准与产业监管机制

行业调查显示，当前微生态制剂生产质控合格率仅为78.6%，肠菌库管理标准差异率达53%，严重制约技术推广的公信力。亟需构建"三位一体"标准化体系：①建立《人体微生态检测实验室建设规范》，明确qPCR检测平台、代谢组学分析仪等22项设备配置标准；②出台《微生态制剂生产质量管理规范》，对菌株分离、冻干工艺等36个关键控制点实施飞行检查；③制定《肠道菌群库建设与运营标准》，建立供体筛选"五维评估模型"（基因组、代谢组、免疫组、病原组、心理评估），开发基于区块链技术的全流程溯源系统（数据上链率100%）。建议由国家药监局设立专项稽查办公室，对未通过GMP认证的企业实施产品准入限制。

4.3.4 区域化技术枢纽与县域辐射网络

针对当前地市级微生态诊疗中心覆盖率不足12%的现状，建议实施"百城千县"建设工程：①遴选300个地级市建设示范中心，配置智能菌群分析系统、自动化制备工作站等核心设备；②构建"1+N"辐射网络，每个中心对口支持8-10个县级医疗机构，开展远程会诊、技术带教等服务；③建立效益评估模型，经测算示范中心建设投入产出比可达1:4.3，同步带动区域IVD产业、冷链物流等相关行业发展。建议将项目建设纳入《县级医院能力提升工程》，中央财政给予设备配置专项补助。

4.3.5 长效发展保障机制

建议构建政产学研协同创新体系：政策端将技术推广纳入《健康中国2030规划纲要》考核指标；学术端成立中华医学会微生态治疗分会，开发继续教育云平台（年培训量≥10万人次）；产业端组建由央企牵头的技术创新联盟，研发便携式检测设备（成本控制＜5000元/台）；临床端建立多中心真实世界研究（目标10万例），开发疗效预测模型（AUC≥0.85）。通过建立ISO15189认证实验室网络，实施室间质评（CV值＜15%），最终形成覆盖"检测-诊断-治疗-随访"全流程的质量控制体系，为技术推广提供可持续保障。

5. 2024年中国肿瘤与微生态学科十大前沿进展（新成果、新技术、大事记）

（1）咽峡炎链球菌促进胃炎症、萎缩和肿瘤发生

胃癌是全球第五大常见癌症及癌症死亡主因之一，幽门螺杆菌作为I类致癌物虽为主要风险因子，但仅1%-3%感染者最终发展为胃癌，提示其他因素参与癌变过程。近年研究发现，胃黏膜中非Hp微生物组的失调可能在胃癌发生中起关键作用，但其具体驱动菌尚未明确。香港中文大学研究团队近期鉴定出一种新型促胃癌菌-咽峡炎链球菌，其在胃癌患者胃黏膜中显著富集。动物实验显示，咽峡炎链球菌可在胃内定植并诱发急性胃炎，长期感染可自发诱导慢性胃炎→胃萎缩→肠上皮化生→异型增生等癌前病变，并在多模型中加速胃肿瘤发生。咽峡炎链球菌通过破坏胃屏障功能、扰乱菌群平衡、促进增殖及抑制凋亡驱动癌变。咽峡炎链球菌表面蛋白TMPC与胃上皮细胞受体ANXA2结合，增强细菌定植能力并激活致癌MAPK信号通路。该研究首次揭示咽峡炎链球菌通过TMPC-ANXA2-MAPK轴直接促进胃肿瘤发生，为非Hp微生物在GC病因学中的作用提供新证据，为早期干预策略开发奠定理论基础。

（2）多中心研究揭示结直肠癌代谢物动态图谱与诊断突破

CRC从正常黏膜向腺瘤及癌变的代谢演变机制尚不明确。香港中文大学、昆明医科大学一附院及南京医科大学联合团队通过多中心研究，系统解析了CRC进展中的血浆和粪便代谢物特征及其促癌机制，并评估其诊断价值。研究整合4个独立队列（n=1251）样本，包括373例粪便/血浆发现队列及878例血浆验证队列。代谢组学分析揭示，CRC患者血浆中油酸显著富集而别胆酸缺失，且这一变化在正常→腺瘤→CRC进程中呈渐进趋势。实验证实油酸通过结合α-烯醇酶激活PI3K/Akt通路驱动肿瘤增殖，而别胆酸通过法尼醇X受体-1抑制MAPK通路发挥抗肿瘤作用。临床验证显示，基于17种血浆代谢物构建的诊断模型在4个队列中AUC达0.848-0.987，显著优于粪便代谢物，尤其对腺瘤和早期CRC具有高灵敏性。该研究首次系统性阐明CRC代谢物动态调控网络及机制，为基于代谢标志物的早筛策略提供了重要理论依据和转化潜力。

（3）具核梭杆菌通过丁酸增强MSS大肠癌免疫治疗

微卫星稳定型CRC对免疫检查点抑制剂响应率低，香港中文大学研究团队发现，促癌菌具核梭菌通过代谢产物丁酸重塑肿瘤免疫微环境，显著提升微卫星稳定型CRC对抗PD-1治疗的敏感性。临床分析显示，瘤内具核梭菌高丰度的微卫星稳定型CRC患者对抗PD-1治疗反应更佳，提示具核梭菌可作为疗效预测标志物。FMT证实具核梭菌富集的肠道菌群可增强小鼠对抗PD-1治疗的响应。具核梭菌通过分泌丁酸抑制CD8+肿瘤浸润淋巴细胞中的组蛋白去乙酰化酶，诱导Tbx21启动子区组蛋白H3K27乙酰化，从而促进Tbx21表达。TBX21通过抑制PD-1转录减轻T细胞耗竭，增强其抗肿瘤功能。动物模型及患者类器官实验进一步验证，敲除具核梭菌产丁酸基因或直接阻断丁酸信号可消除其对免疫治疗的增敏作用。该研究首次阐明菌群代谢物通过表观遗传调控增强免疫疗效的机制，为微卫星稳定型CRC精准免疫治疗提供了新靶点。

（4）基因工程改造噬菌体纳米纤维用于肿瘤靶向免疫治疗

香港中文大学团队创新性设计出一种靶向PD-L1的丝状噬菌体，通过阻断PD-1/PD-L1通路激活抗肿瘤免疫反应，为免疫治疗提供新策略。研究选用fd噬菌体作为载体，其可通过感染大肠杆菌在发酵罐中实现低成本大规模生产，数小时内快速增殖。团队筛选出高亲和力PD-L1结合肽HH，将其融合至噬菌体表面pVIII蛋白，使单个噬菌体展示约3900个阻断分子，大幅提高疗效并降低生产成本。进一步通过基因工程构建双功能噬菌体fd-HH-IP，兼具靶向黑色素瘤及阻断PD-1/PD-L1互作能力。体内外实验证实，该噬菌体能精准定位肿瘤组织，有效抑制PD-1/PD-L1信号轴，阻断肿瘤细胞免疫逃逸，显著延缓肿瘤生长且无显著毒性。研究首次将噬菌体工程与免疫检查点抑制结合，展现了其在高效、经济型肿瘤免疫治疗中的转化潜力，为开发新型生物纳米治疗制剂开辟了方向。

（5）菌群代谢脱氧胆酸抑制CD8+ T细胞驱动结直肠癌

CRC患者肠道中次级胆汁酸脱氧胆酸浓度显著升高，但其促癌机制尚未明确。中国科学技术大学研究团队最新研究发现，次级胆汁酸脱氧胆酸通过抑制CD8+ T细胞功能驱动CRC进展，为免疫干预提供新靶点。研究发现次级胆汁酸脱氧胆酸可显著削弱CD8+ T细胞的抗肿瘤效应功能，促进小鼠CRC生长。次级胆汁酸脱氧胆酸可结合细胞膜钙泵增强其活性，减少胞内钙离子积累，进而抑制钙依赖性NFAT2信号通路，导致CD8+ T细胞转录活性下降。临床分析显示CRC患者粪便次级胆汁酸脱氧胆酸水平及其细菌合成基因baiF表达与CD8+ T细胞功能呈负相关。进一步实验证实，携带次级胆汁酸脱氧胆酸合成基因的肠菌抑制免疫应答并加速肿瘤进展，而靶向干预次级胆汁酸脱氧胆酸代谢可逆转这一效应。该研究首次阐明次级胆汁酸脱氧胆酸通过免疫抑制途径促进CRC的分子机制，揭示了调控菌群代谢物-免疫互作网络的潜在治疗价值，为CRC防治策略开辟新方向。

（6）结直肠癌肠道古菌动态演变与跨界诊断新策略

CRC发展过程中肠道古菌的演变规律及其临床价值尚未明确。香港中文大学团队通过整合全球7个国家10个独立队列及1个内部队列（共2101例宏基因组样本，含748例CRC、471例腺瘤及882例健康对照），系统解析了CRC进展中古菌-细菌互作网络。关键发现显示，CRC中减少的产甲烷古菌与产丁酸细菌的共生互作增强，且甲烷代谢相关基因通路异常激活，提示古菌通过调节菌群代谢促进肿瘤进展。基于古菌与细菌的跨界标志物，团队构建的无创诊断模型在跨队列验证中AUC达0.744-0.931，显著优于单一微生物界别模型。该研究首次揭示古菌在CRC发生中的动态调控作用，为基于多界微生物标志物的精准早筛提供了创新方案。

（7）乳酸乳球菌HkyuLL 10可抑制结直肠肿瘤发生并恢复肠道微生物群

CRC是全球癌症相关死亡的第二大原因，早期识别有效预防策略对降低CRC负担至关重要。菌群失调可破坏肠道稳态并促进CRC进展。目前通过益生菌、粪菌移植等方式调节菌群的研究备受关注，其中益生菌因能分泌抗肿瘤蛋白或代谢物展现出独特优势。香港中文大学团队通过分析489例CRC患者与536例健康人粪便，发现患者肠道乳酸乳球菌丰度显著降低，并成功从健康样本中分离出新菌株HkyuLL 10。在ApcMin/+突变小鼠和化学诱导CRC模型中，补充HkyuLL 10可抑制肿瘤生成，并通过富集约氏乳杆菌等益生菌改善菌群失调。此外，团队鉴定出HkyuLL 10分泌的功能性蛋白α-甘露糖苷酶能在体外实验中显著抑制CRC细胞及患者类器官增殖，并在异种移植模型中减少肿瘤体积。并且HkyuLL 10通过双重机制调控菌群稳态及分泌α-甘露糖苷酶抑制CRC进展，为开发益生菌辅助治疗或预防策略提供了科学依据，具有重要临床转化潜力。

（8）共生梭菌通过分泌支链氨基酸促进肠癌发生

CRC发生与肠道菌群失调密切相关，但其代谢调控网络尚未完全阐明。上海交通大学医学院附属仁济医院研究团队最新研究发现，共生梭菌通过分泌支链氨基酸重塑结直肠胆固醇代谢并调控干细胞稳态，从而驱动CRC进展。研究显示，共生梭菌在CRC患者肠道中显著富集，其产生的支链氨基酸可激活宿主细胞内胆固醇合成关键酶HMGCR，促使胆固醇异常积累。这种代谢重编程不仅破坏肠道干细胞稳态，还通过激活Wnt/β-catenin信号通路促进肿瘤细胞增殖。动物实验进一步证实，抑制共生梭菌或其支链氨基酸代谢可显著降低胆固醇水平并延缓肿瘤生长。该研究首次揭示共生梭菌通过“菌群-代谢-干细胞”轴促癌的分子机制，为靶向肠道菌群代谢干预CRC提供了新策略，具有潜在的临床转化价值。

（9）具核梭杆菌促进肠癌发生发展

具核梭杆菌在结直肠癌CRC中的促癌作用机制尚待深入解析。上海交通大学医学院附属仁济医院研究团队发现，具核梭杆菌黏附素RadD通过靶向宿主受体CD147激活致癌信号通路，驱动CRC进展。研究通过全基因组筛选锁定radD基因，证实其介导具核梭杆菌与CRC细胞的黏附。机制上，RadD直接结合CRC细胞表面高表达的CD147，激活PI3K–AKT–NF–κB–MMP9级联反应，显著增加Apc突变小鼠的肿瘤发生率。临床分析显示CRC组织中radD基因水平与肿瘤信号通路活性及患者不良预后呈正相关。动物模型中，阻断RadD-CD147互作可减少具核梭杆菌定植并抑制致癌效应。该研究首次阐明具核梭杆菌通过RadD-CD147互作重塑肿瘤微环境的分子机制，为开发靶向菌群-宿主互作的抗CRC疗法提供了新方向。

（10）左右半结肠癌多组学特征与菌群-宿主互作治疗新靶点

右半结肠癌与左半结肠癌在临床特征及预后上存在显著差异，但其分子机制尚不明确。复旦大学附属肿瘤医院研究团队通过多组学分析，系统解析了右半结肠癌与左半结肠癌在肠道菌群、代谢物及宿主基因组层面的独特特征。研究发现，右半结肠癌患者中，细菌Flavonifractor plautii、具核梭菌与代谢物L-苯丙氨酸显著富集，且宿主基因PHLDA1/WBP1信号受抑制；而左半结肠癌患者以细菌Bacteroides sp. A1C1、微小微单胞菌及代谢物L-瓜氨酸/D-鸟氨酸为特征，伴随TCF25、HLA-DRB5等基因激活。

多组学关联分析揭示，右半结肠癌富集的菌群通过驱动L-苯丙氨酸积累抑制WBP1通路，而左半结肠癌的菌群则通过代谢物D-鸟氨酸和L-瓜氨酸激活TCF25等基因。这些发现首次阐明右半结肠癌与左半结肠癌在菌群-代谢-宿主基因互作网络的差异，提示肿瘤发生部位特异性调控机制。研究为开发基于靶向肠道菌群-宿主互作的精准治疗策略提供了理论依据，有望改善结直肠癌个体化治疗效率。

【主编】

王 强   武汉科技大学医学院

郭 智   深圳大学附属南山医院

谭晓华   中国人民解放军总医院第七医学中心

【副主编】

吴清明   武汉科技大学医学院

舒 榕   湖北省第三人民医院

黄自明   湖北省妇幼保健院

李小安   绵阳市中心医院

梁 婧   山东第一医科大学第一附属医院

【编委】（按姓氏拼音排序）

刘 姗   深圳大学附属南山医院

王 钧   香港大学深圳医院

钟 楠   深圳大学附属南山医院

胡伟国   武汉大学人民医院

邵 亮   武汉大学中南医院

余春姣   湖北省妇幼保健院

夏 涛   湖北省第三人民医院

李 磊   武汉亚心总医院

何明心   深圳大学附属南山医院

王小梅   武汉科技大学医学院

万京桦   武汉科技大学医学院

向晓晨   武汉科技大学医学院

孟景晔   深圳市第三人民医院

许晓军   中山大学附属第七医院

王 亮   首都医科大学附属北京同仁医院

吴 为   广东省公共卫生研究院

周 浩   华中科技大学同济医学院附属协和医院

杨文燕   山东第一医科大学

乔明强   山西大学生命科学学院

任 骅   南方科技大学医学院

瞿 嵘   惠州市中心人民医院

张宏艳   解放军总医院第三医学中心

张育葵   湖北中医药大学附属襄阳中医医院

胡碧川   襄阳市中西医结合医院

陈 丰   华中科技大学同济医学院附属武汉中心医院

★

参考文献（向上滑动阅览）

[1] THOMAS S, IZARD J, WALSH E, et al. The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists [J]. Cancer Res, 2017, 77(8): 1783-812. DOI: 10.1158/0008-5472.Can-16-2929.

[2] HANAHAN D. Hallmarks of Cancer: New Dimensions [J]. Cancer Discov, 2022, 12(1): 31-46. DOI: 10.1158/2159-8290.Cd-21-1059.

[3] JAYE K, LI C G, BHUYAN D J. The complex interplay of gut microbiota with the five most common cancer types: From carcinogenesis to therapeutics to prognoses [J]. Critical Reviews in Oncology/Hematology, 2021, 165(103429. DOI: https://doi.org/10.1016/j.critrevonc.2021.103429.

[4] CAO Y, XIA H, TAN X, et al. Intratumoural microbiota: a new frontier in cancer development and therapy [J]. Signal Transduction and Targeted Therapy, 2024, 9(1): 15. DOI: 10.1038/s41392-023-01693-0.

[5] ZHAO L-Y, MEI J-X, YU G, et al. Role of the gut microbiota in anticancer therapy: from molecular mechanisms to clinical applications [J]. Signal Transduction and Targeted Therapy, 2023, 8(1): 201. DOI: 10.1038/s41392-023-01406-7.

[6] KUNIKA, FREY N, RANGREZ A Y. Exploring the Involvement of Gut Microbiota in Cancer Therapy-Induced Cardiotoxicity [J]. Int J Mol Sci, 2023, 24(8): DOI: 10.3390/ijms24087261.

[7] SEPICH-POORE G D, ZITVOGEL L, STRAUSSMAN R, et al. The microbiome and human cancer [J]. Science, 2021, 371(6536): DOI: 10.1126/science.abc4552.

[8] ALEXANDER J L, WILSON I D, TEARE J, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity [J]. Nat Rev Gastroenterol Hepatol, 2017, 14(6): 356-65. DOI: 10.1038/nrgastro.2017.20.

[9] PAASKE S E, BAUMWALL S M D, RUBAK T, et al. Real-world Effectiveness of Fecal Microbiota Transplantation for First or Second Clostridioides difficile Infection [J]. Clinical Gastroenterology and Hepatology, 2024, DOI: https://doi.org/10.1016/j.cgh.2024.05.038.

[10] FORSLUND K, SUNAGAWA S, KULTIMA J R, et al. Country-specific antibiotic use practices impact the human gut resistome [J]. Genome Res, 2013, 23(7): 1163-9. DOI: 10.1101/gr.155465.113.

[11] BUFFIE C G, PAMER E G. Microbiota-mediated colonization resistance against intestinal pathogens [J]. Nat Rev Immunol, 2013, 13(11): 790-801. DOI: 10.1038/nri3535.

[12] MONTASSIER E, GASTINNE T, VANGAY P, et al. Chemotherapy-driven dysbiosis in the intestinal microbiome [J]. Aliment Pharmacol Ther, 2015, 42(5): 515-28. DOI: 10.1111/apt.13302.

[13] GALLOWAY-PEñA J R, SMITH D P, SAHASRABHOJANE P, et al. The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia [J]. Cancer, 2016, 122(14): 2186-96. DOI: 10.1002/cncr.30039.

[14] GALLOWAY-PEñA J R, SMITH D P, SAHASRABHOJANE P, et al. Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients [J]. Genome Med, 2017, 9(1): 21. DOI: 10.1186/s13073-017-0409-1.

[15] WEBER D, JENQ R R, PELED J U, et al. Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation [J]. Biol Blood Marrow Transplant, 2017, 23(5): 845-52. DOI: 10.1016/j.bbmt.2017.02.006.

[16] TAUR Y, JENQ R R, PERALES M A, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation [J]. Blood, 2014, 124(7): 1174-82. DOI: 10.1182/blood-2014-02-554725.

[17] HOLLER E, BUTZHAMMER P, SCHMID K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease [J]. Biol Blood Marrow Transplant, 2014, 20(5): 640-5. DOI: 10.1016/j.bbmt.2014.01.030.

[18] STEIN-THOERINGER C K, NICHOLS K B, LAZRAK A, et al. Lactose drives Enterococcus expansion to promote graft-versus-host disease [J]. Science, 2019, 366(6469): 1143-9. DOI: 10.1126/science.aax3760.

[19] USTUN C, YOUNG J H, PAPANICOLAOU G A, et al. Bacterial blood stream infections (BSIs), particularly post-engraftment BSIs, are associated with increased mortality after allogeneic hematopoietic cell transplantation [J]. Bone Marrow Transplant, 2019, 54(8): 1254-65. DOI: 10.1038/s41409-018-0401-4.

[20] HARRIS B, MORJARIA S M, LITTMANN E R, et al. Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation [J]. Am J Respir Crit Care Med, 2016, 194(4): 450-63. DOI: 10.1164/rccm.201507-1491OC.

[21] PELED J U, GOMES A L C, DEVLIN S M, et al. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation [J]. N Engl J Med, 2020, 382(9): 822-34. DOI: 10.1056/NEJMoa1900623.

[22] KUSAKABE S, FUKUSHIMA K, MAEDA T, et al. Pre- and post-serial metagenomic analysis of gut microbiota as a prognostic factor in patients undergoing haematopoietic stem cell transplantation [J]. Br J Haematol, 2020, 188(3): 438-49. DOI: 10.1111/bjh.16205.

[23] TAUR Y, COYTE K, SCHLUTER J, et al. Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant [J]. Sci Transl Med, 2018, 10(460): DOI: 10.1126/scitranslmed.aap9489.

[24] RASHIDI A, EBADI M, REHMAN T U, et al. Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML [J]. J Clin Oncol, 2023, 41(34): 5306-19. DOI: 10.1200/jco.22.02366.

[25] SHONO Y, VAN DEN BRINK M R M. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation [J]. Nat Rev Cancer, 2018, 18(5): 283-95. DOI: 10.1038/nrc.2018.10.

[26] DEFILIPP Z, PELED J U, LI S, et al. Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity [J]. Blood Adv, 2018, 2(7): 745-53. DOI: 10.1182/bloodadvances.2018017731.

[27] MALARD F, VEKHOFF A, LAPUSAN S, et al. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients [J]. Nat Commun, 2021, 12(1): 3084. DOI: 10.1038/s41467-021-23376-6.

[28] MANCINI N, GRECO R, PASCIUTA R, et al. Enteric Microbiome Markers as Early Predictors of Clinical Outcome in Allogeneic Hematopoietic Stem Cell Transplant: Results of a Prospective Study in Adult Patients [J]. Open Forum Infect Dis, 2017, 4(4): ofx215. DOI: 10.1093/ofid/ofx215.

[29] BILINSKI J, GRZESIOWSKI P, SORENSEN N, et al. Fecal Microbiota Transplantation in Patients With Blood Disorders Inhibits Gut Colonization With Antibiotic-Resistant Bacteria: Results of a Prospective, Single-Center Study [J]. Clin Infect Dis, 2017, 65(3): 364-70. DOI: 10.1093/cid/cix252.

[30] RASHIDI A, EBADI M, REHMAN T U, et al. Long- and short-term effects of fecal microbiota transplantation on antibiotic resistance genes: results from a randomized placebo-controlled trial [J]. Gut Microbes, 2024, 16(1): 2327442. DOI: 10.1080/19490976.2024.2327442.

[31] FORCINA A, LORENTINO F, MARASCO V, et al. Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation [J]. Biol Blood Marrow Transplant, 2018, 24(7): 1476-82. DOI: 10.1016/j.bbmt.2018.02.021.

[32] SADOWSKA-KLASA A, PIEKARSKA A, PREJZNER W, et al. Colonization with multidrug-resistant bacteria increases the risk of complications and a fatal outcome after allogeneic hematopoietic cell transplantation [J]. Ann Hematol, 2018, 97(3): 509-17. DOI: 10.1007/s00277-017-3205-5.

[33] BATTIPAGLIA G, MALARD F, RUBIO M T, et al. Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria [J]. Haematologica, 2019, 104(8): 1682-8. DOI: 10.3324/haematol.2018.198549.

[34] INNES A J, MULLISH B H, GHANI R, et al. Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation [J]. Front Cell Infect Microbiol, 2021, 11(684659. DOI: 10.3389/fcimb.2021.684659.

[35] SHALLIS R M, TERRY C M, LIM S H. Changes in intestinal microbiota and their effects on allogeneic stem cell transplantation [J]. American Journal of Hematology, 2018, 93(1): 122-8. DOI: https://doi.org/10.1002/ajh.24896.

[36] WOODWORTH M H, CONRAD R E, HALDOPOULOS M, et al. Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement [J]. Sci Transl Med, 2023, 15(720): eabo2750. DOI: 10.1126/scitranslmed.abo2750.

[37] BRITTON R A, YOUNG V B. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile [J]. Gastroenterology, 2014, 146(6): 1547-53. DOI: 10.1053/j.gastro.2014.01.059.

[38] ILETT E E, HELLEBERG M, REEKIE J, et al. Incidence Rates and Risk Factors of Clostridioides difficile Infection in Solid Organ and Hematopoietic Stem Cell Transplant Recipients [J]. Open Forum Infect Dis, 2019, 6(4): ofz086. DOI: 10.1093/ofid/ofz086.

[39] ROSIGNOLI C, PETRUZZELLIS G, RADICI V, et al. Risk Factors and Outcome of C. difficile Infection after Hematopoietic Stem Cell Transplantation [J]. J Clin Med, 2020, 9(11): DOI: 10.3390/jcm9113673.

[40] JABR R, EL ATROUNI W, SHUNE L, et al. Clostridioides difficile Infection and Risk of Acute Graft-versus-Host Disease among Allogeneic Hematopoietic Stem Cell Transplantation Recipients [J]. Transplant Cell Ther, 2021, 27(2): 176.e1-.e8. DOI: 10.1016/j.jtct.2020.10.009.

[41] JAIN T, CROSWELL C, URDAY-CORNEJO V, et al. Clostridium Difficile Colonization in Hematopoietic Stem Cell Transplant Recipients: A Prospective Study of the Epidemiology and Outcomes Involving Toxigenic and Nontoxigenic Strains [J]. Biol Blood Marrow Transplant, 2016, 22(1): 157-63. DOI: 10.1016/j.bbmt.2015.07.020.

[42] FRIEDMAN N D, POLLARD J, STUPART D, et al. Prevalence of Clostridium difficile colonization among healthcare workers [J]. BMC Infect Dis, 2013, 13(459. DOI: 10.1186/1471-2334-13-459.

[43] ZACHARIOUDAKIS I M, ZERVOU F N, PLIAKOS E E, et al. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis [J]. Am J Gastroenterol, 2015, 110(3): 381-90; quiz 91. DOI: 10.1038/ajg.2015.22.

[44] CHOPRA T, ALANGADEN G J, CHANDRASEKAR P. Clostridium difficile infection in cancer patients and hematopoietic stem cell transplant recipients [J]. Expert Rev Anti Infect Ther, 2010, 8(10): 1113-9. DOI: 10.1586/eri.10.95.

[45] KINNEBREW M A, LEE Y J, JENQ R R, et al. Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation [J]. PLoS One, 2014, 9(3): e90158. DOI: 10.1371/journal.pone.0090158.

[46] BUFFIE C G, BUCCI V, STEIN R R, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile [J]. Nature, 2015, 517(7533): 205-8. DOI: 10.1038/nature13828.

[47] LUO Y, ZHANG S, SHANG H, et al. Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis [J]. Front Cell Infect Microbiol, 2022, 12(801475. DOI: 10.3389/fcimb.2022.801475.

[48] PRAYAG P S, PATWARDHAN S A, AJAPUJE P S, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India [J]. Indian J Crit Care Med, 2024, 28(2): 106-10. DOI: 10.5005/jp-journals-10071-24607.

[49] CHONG P P, KOH A Y. The gut microbiota in transplant patients [J]. Blood Rev, 2020, 39(100614. DOI: 10.1016/j.blre.2019.100614.

[50] DEFILIPP Z, HOHMANN E, JENQ R R, et al. Fecal Microbiota Transplantation: Restoring the Injured Microbiome after Allogeneic Hematopoietic Cell Transplantation [J]. Biol Blood Marrow Transplant, 2019, 25(1): e17-e22. DOI: 10.1016/j.bbmt.2018.10.022.

[51] JENQ R R, TAUR Y, DEVLIN S M, et al. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease [J]. Biol Blood Marrow Transplant, 2015, 21(8): 1373-83. DOI: 10.1016/j.bbmt.2015.04.016.

[52] GU Z, XIONG Q, WANG L, et al. The impact of intestinal microbiota in antithymocyte globulin-based myeloablative allogeneic hematopoietic cell transplantation [J]. Cancer, 2022, 128(7): 1402-10. DOI: 10.1002/cncr.34091.

[53] JENQ R R, UBEDA C, TAUR Y, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation [J]. J Exp Med, 2012, 209(5): 903-11. DOI: 10.1084/jem.20112408.

[54] BIAGI E, ZAMA D, NASTASI C, et al. Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT [J]. Bone Marrow Transplant, 2015, 50(7): 992-8. DOI: 10.1038/bmt.2015.16.

[55] GAVRIILAKI M, SAKELLARI I, ANAGNOSTOPOULOS A, et al. The Impact of Antibiotic-Mediated Modification of the Intestinal Microbiome on Outcomes of Allogeneic Hematopoietic Cell Transplantation: Systematic Review and Meta-Analysis [J]. Biol Blood Marrow Transplant, 2020, 26(9): 1738-46. DOI: 10.1016/j.bbmt.2020.05.011.

[56] KAKIHANA K, FUJIOKA Y, SUDA W, et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut [J]. Blood, 2016, 128(16): 2083-8. DOI: 10.1182/blood-2016-05-717652.

[57] GOLOSHCHAPOV O, CHUKHLOVIN A, BAKIN E, et al. Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety [J]. Terapevticheskii arkhiv, 2020, 92(7): 43-54. DOI: 10.26442/00403660.2020.07.000773.

[58] QIAO X, BILI?SKI J, WANG L, et al. Safety and efficacy of fecal microbiota transplantation in the treatment of graft-versus-host disease [J]. Bone Marrow Transplant, 2023, 58(1): 10-9. DOI: 10.1038/s41409-022-01824-1.

[59] BILINSKI J, LIS K, TOMASZEWSKA A, et al. Fecal microbiota transplantation in patients with acute and chronic graft-versus-host disease-spectrum of responses and safety profile. Results from a prospective, multicenter study [J]. Am J Hematol, 2021, 96(3): E88-e91. DOI: 10.1002/ajh.26077.

[60] SPINDELBOECK W, HALWACHS B, BAYER N, et al. Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study [J]. Ther Adv Hematol, 2021, 12(20406207211058333. DOI: 10.1177/20406207211058333.

[61] SPINDELBOECK W, SCHULZ E, UHL B, et al. Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-host-disease [J]. Haematologica, 2017, 102(5): e210-e3. DOI: 10.3324/haematol.2016.154351.

[62] KAITO S, TOYA T, YOSHIFUJI K, et al. Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease [J]. Blood Adv, 2018, 2(22): 3097-101. DOI: 10.1182/bloodadvances.2018024968.

[63] MALARD F, LOSCHI M, HUYNH A, et al. Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial [J]. EClinicalMedicine, 2023, 62(102111. DOI: 10.1016/j.eclinm.2023.102111.

[64] ZHAO Y, LI X, ZHOU Y, et al. Safety and Efficacy of Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD Patients: Interim Results From FMT2017002 Trial [J]. Front Immunol, 2021, 12(678476. DOI: 10.3389/fimmu.2021.678476.

[65] VAN LIER Y F, DAVIDS M, HAVERKATE N J E, et al. Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients [J]. Sci Transl Med, 2020, 12(556): DOI: 10.1126/scitranslmed.aaz8926.

[66] LEE C H, STEINER T, PETROF E O, et al. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial [J]. Jama, 2016, 315(2): 142-9. DOI: 10.1001/jama.2015.18098.

[67] KAO D, ROACH B, SILVA M, et al. Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial [J]. Jama, 2017, 318(20): 1985-93. DOI: 10.1001/jama.2017.17077.

[68] ZEISER R, VON BUBNOFF N, BUTLER J, et al. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease [J]. N Engl J Med, 2020, 382(19): 1800-10. DOI: 10.1056/NEJMoa1917635.

[69] FEARON K, STRASSER F, ANKER S D, et al. Definition and classification of cancer cachexia: an international consensus [J]. Lancet Oncol, 2011, 12(5): 489-95. DOI: 10.1016/s1470-2045(10)70218-7.

[70] KALANTAR-ZADEH K, RHEE C, SIM J J, et al. Why cachexia kills: examining the causality of poor outcomes in wasting conditions [J]. J Cachexia Sarcopenia Muscle, 2013, 4(2): 89-94. DOI: 10.1007/s13539-013-0111-0.

[71] ZAORSKY N G, CHURILLA T M, EGLESTON B L, et al. Causes of death among cancer patients [J]. Ann Oncol, 2017, 28(2): 400-7. DOI: 10.1093/annonc/mdw604.

[72] BINDELS L B, BECK R, SCHAKMAN O, et al. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model [J]. PLoS One, 2012, 7(6): e37971. DOI: 10.1371/journal.pone.0037971.

[73] BINDELS L B, NEYRINCK A M, CLAUS S P, et al. Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia [J]. Isme j, 2016, 10(6): 1456-70. DOI: 10.1038/ismej.2015.209.

[74] DE CLERCQ N C, VAN DEN ENDE T, PRODAN A, et al. Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer: A Randomized, Double-blind, Placebo-Controlled, Phase II Study [J]. Clin Cancer Res, 2021, 27(13): 3784-92. DOI: 10.1158/1078-0432.Ccr-20-4918.

[75] HERREMANS K M, RINER A N, CAMERON M E, et al. The Microbiota and Cancer Cachexia [J]. Int J Mol Sci, 2019, 20(24): DOI: 10.3390/ijms20246267.

[76] BAGCHI S, YUAN R, ENGLEMAN E G. Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance [J]. Annual Review of Pathology: Mechanisms of Disease, 2021, 16(Volume 16, 2021): 223-49. DOI: https://doi.org/10.1146/annurev-pathol-042020-042741.

[77] SHARMA P, SIDDIQUI B A, ANANDHAN S, et al. The Next Decade of Immune Checkpoint Therapy [J]. Cancer Discovery, 2021, 11(4): 838-57. DOI: 10.1158/2159-8290.Cd-20-1680.

[78] YAP T A, PARKES E E, PENG W, et al. Development of Immunotherapy Combination Strategies in Cancer [J]. Cancer Discovery, 2021, 11(6): 1368-97. DOI: 10.1158/2159-8290.Cd-20-1209.

[79] SHARPE A H, PAUKEN K E. The diverse functions of the PD1 inhibitory pathway [J]. Nature Reviews Immunology, 2018, 18(3): 153-67. DOI: 10.1038/nri.2017.108.

[80] SANMAMED M F, CHEN L. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization [J]. Cell, 2018, 175(2): 313-26. DOI: https://doi.org/10.1016/j.cell.2018.09.035.

[81] HASLAM A, PRASAD V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs [J]. JAMA Network Open, 2019, 2(5): e192535-e. DOI: 10.1001/jamanetworkopen.2019.2535.

[82] PARK E M, CHELVANAMBI M, BHUTIANI N, et al. Targeting the gut and tumor microbiota in cancer [J]. Nature Medicine, 2022, 28(4): 690-703. DOI: 10.1038/s41591-022-01779-2.

[83] BARUCH E N, YOUNGSTER I, BEN-BETZALEL G, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients [J]. Science, 2021, 371(6529): 602-9. DOI: 10.1126/science.abb5920.

[84] DAVAR D, DZUTSEV A K, MCCULLOCH J A, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients [J]. Science, 2021, 371(6529): 595-602. DOI: 10.1126/science.abf3363.

[85] BORGERS J S W, BURGERS F H, TERVEER E M, et al. Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial [J]. BMC Cancer, 2022, 22(1): 1366. DOI: 10.1186/s12885-022-10457-y.

[86] ROUTY B, LENEHAN J G, MILLER W H, JR., et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial [J]. Nat Med, 2023, 29(8): 2121-32. DOI: 10.1038/s41591-023-02453-x.

[87] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2018 [J]. CA Cancer J Clin, 2018, 68(1): 7-30. DOI: 10.3322/caac.21442.

[88] CAPITANIO U, MONTORSI F. Renal cancer [J]. Lancet, 2016, 387(10021): 894-906. DOI: 10.1016/s0140-6736(15)00046-x.

[89] CHOUEIRI T K, MOTZER R J. Systemic Therapy for Metastatic Renal-Cell Carcinoma [J]. N Engl J Med, 2017, 376(4): 354-66. DOI: 10.1056/NEJMra1601333.

[90] GORE M E, SZCZYLIK C, PORTA C, et al. Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma [J]. Br J Cancer, 2015, 113(1): 12-9. DOI: 10.1038/bjc.2015.196.

[91] STERNBERG C N, DAVIS I D, MARDIAK J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial [J]. J Clin Oncol, 2010, 28(6): 1061-8. DOI: 10.1200/jco.2009.23.9764.

[92] MOTZER R J, HUTSON T E, TOMCZAK P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma [J]. N Engl J Med, 2007, 356(2): 115-24. DOI: 10.1056/NEJMoa065044.

[93] JONASCH E, SLACK R S, GEYNISMAN D M, et al. Phase II Study of Two Weeks on, One Week off Sunitinib Scheduling in Patients With Metastatic Renal Cell Carcinoma [J]. J Clin Oncol, 2018, 36(16): 1588-93. DOI: 10.1200/jco.2017.77.1485.

[94] IANIRO G, ROSSI E, THOMAS A M, et al. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma [J]. Nat Commun, 2020, 11(1): 4333. DOI: 10.1038/s41467-020-18127-y.

[95] BILI?SKI J, JASI?SKI M, TOMASZEWSKA A, et al. Fecal microbiota transplantation with ruxolitinib as a treatment modality for steroid-refractory/dependent acute, gastrointestinal graft-versus-host disease: A case series [J]. Am J Hematol, 2021, 96(12): E461-e3. DOI: 10.1002/ajh.26365.

[96] QI X, LI X, ZHAO Y, et al. Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study [J]. Front Immunol, 2018, 9(2195. DOI: 10.3389/fimmu.2018.02195.

[97] LIU Y, ZHAO Y, QI J, et al. Fecal microbiota transplantation combined with ruxolitinib as a salvage treatment for intestinal steroid-refractory acute GVHD [J]. Experimental Hematology & Oncology, 2022, 11(1): 96. DOI: 10.1186/s40164-022-00350-6.

[98] GOESER F, SIFFT B, STEIN-THOERINGER C, et al. Fecal microbiota transfer for refractory intestinal graft-versus-host disease - Experience from two German tertiary centers [J]. Eur J Haematol, 2021, 107(2): 229-45. DOI: 10.1111/ejh.13642.

[99] GHANI R, MULLISH B H, MCDONALD J A K, et al. Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms [J]. Clin Infect Dis, 2021, 72(8): 1444-7. DOI: 10.1093/cid/ciaa948.

[100]  OLESEN S W, LEIER M M, ALM E J, et al. Searching for superstool: maximizing the therapeutic potential of FMT [J]. Nat Rev Gastroenterol Hepatol, 2018, 15(7): 387-8. DOI: 10.1038/s41575-018-0019-4.

[101]  HABIBI S, RASHIDI A. Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward [J]. Gut Microbes, 2023, 15(1): 2229567. DOI: 10.1080/19490976.2023.2229567.

[102]  DEFILIPP Z, BLOOM P P, TORRES SOTO M, et al. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant [J]. N Engl J Med, 2019, 381(21): 2043-50. DOI: 10.1056/NEJMoa1910437.

[103]  BILINSKI J, LIS K, TOMASZEWSKA A, et al. Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant [J]. Transpl Infect Dis, 2021, 23(1): e13386. DOI: 10.1111/tid.13386.

[104]  ESHEL A, SHARON I, NAGLER A, et al. Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis [J]. Blood Adv, 2022, 6(2): 568-73. DOI: 10.1182/bloodadvances.2021005110.

[105]  BAKKEN J S, BORODY T, BRANDT L J, et al. Treating Clostridium difficile infection with fecal microbiota transplantation [J]. Clin Gastroenterol Hepatol, 2011, 9(12): 1044-9. DOI: 10.1016/j.cgh.2011.08.014.

[106]  DAVIDOVICS Z H, MICHAIL S, NICHOLSON M R, et al. Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition [J]. J Pediatr Gastroenterol Nutr, 2019, 68(1): 130-43. DOI: 10.1097/mpg.0000000000002205.

[107]  CAMMAROTA G, IANIRO G, KELLY C R, et al. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice [J]. Gut, 2019, 68(12): 2111-21. DOI: 10.1136/gutjnl-2019-319548.

[108]  HENIG I, YEHUDAI-OFIR D, ZUCKERMAN T. The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation [J]. Haematologica, 2021, 106(4): 933-46. DOI: 10.3324/haematol.2020.247395.

[109]  VEHRESCHILD M, DUCHER A, LOUIE T, et al. An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones [J]. J Antimicrob Chemother, 2022, 77(4): 1155-65. DOI: 10.1093/jac/dkab474.

[110]  ZHANG F, ZUO T, YEOH Y K, et al. Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease [J]. Nat Commun, 2021, 12(1): 65. DOI: 10.1038/s41467-020-20240-x.

[111]  郭智,王强,郭智,等.肠菌移植制备和质控实验室标准化技术规范中国专家共识（2023版）[J].中国微生态学杂志,2024,36(06):705-711+717.

[112]  中国抗癌协会肿瘤与微生态专业委员会.肠道微生态与肿瘤治疗相关消化系统并发症管理中国专家共识[J].国际肿瘤学杂志,2022,49(12):711-717.

[113]  Wang J, Liang J, He M, et al. Chinese expert consensus on intestinal microecology and management of digestive tract complications related to tumor treatment (version 2022). J Cancer Res Ther,2022;18(7):1835-44.

[114]  Wang Q, Lei Y, Wang J, et al. Expert consensus on the relevance of intestinal microecology and hematopoietic stem cell transplantation. Clin Transplant,2024,;38(1):e15186.

[115]  Guo Z, He M, Shao L, et al. The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease. J Cancer Res Ther, 2024,20(7):1964-1973.

[116]  Wang Q, He M, Liang J, et al.Chinese guidelines for integrated diagnosis and treatment of intestinal microecology technologies in tumor application (2024 Edition). J Cancer Res Ther,2024,20(4):1130-1140.

[117]  中国抗癌协会肿瘤与微生态专业委员会.肠道微生态与造血干细胞移植相关性中国专家共识[J]. 国际肿瘤学杂志,2021,48(3):129-135.

[118]  中国抗癌协会肿瘤与微生态专业委员会.中国抗癌协会肠道微生态技术整合诊治指南（精简版）[J]. 中国肿瘤临床,2023,48(3):919-927.

[119]  Darbandi A,Mirshekar M,Shariati A,et al.The effects of probiotics on reducing thecolorectal cancer surgery complications:A periodic review during 2007-2017.Clinical Nutrition,2020,39(8):2358-2367.

[120]  Arnold M,Abnet CC,Neale RE,et al.Global Burden of 5 Major Types of Gastrointestinal Cancer.Gastroenterology,2020,159(1):335-349.

[121]  Ferreira RM,Pereira-Marques J,Pinto-Ribeiro I,et al.Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota.Gut,2018,67(2):226-236.

[122]  Ma C,Han M,Heinrich B,et al.Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.Science,2018,360(6391):eaan5931.

[123]  Hartmann N,Kronenberg M,Cancer immunity thwarted by the microbiome.Science,2018,360(6391):858-859.

[124]  Coker OO,Nakatsu G,Dai RZ,et al.Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer.Gut,2019,68(4):654-662.

[125]  Jin C,Lagoudas GK,Zhao C,et al.Commensal Microbiota Promote Lung Cancer Development via γδ T Cells.Cell,2019,176(5):998-1013.e16.

[126]  Saus E,Iraola-Guzmán S,Willis JR,et al.Microbiome and colorectal cancer:Roles in carcinogenesis and clinical potential.Molecular Aspects of Medicine,2019,69:93-106.

[127]  Yang J,LiD,Yang Z,et al.Establishing high-accuracy biomarkers for colorectal cancer by comparing fecal microbiomes in patients with healthy families.Gut Microbes,2020,11(4):1-12.

[128]   Thomas AM,ManghiP,Asnicar F,et al.Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with cholinedegradation.Nature Medicine,2019,25(4):667-678.

[129]  Sittipo P,Shim JW,Lee YK,et al.Microbial Metabolites Determine Host Health and the Status of Some Diseases. International Journal of Molecular Sciences,2019,20 (21):26.

[130]  Sittipo P,Lobionda S,Lee YK,et al.Intestinal microbiota and the immune system in metabolic diseases. Journal of Microbiology,2018,56 (3):154-162.

[131]  ZITVOGEL L, DAILLèRE R, ROBERTI M P, et al. Anticancer effects of the microbiome and its products.Nature reviews Microbiology,2017,15(8): 465-78.

[132]  WANG Y, SUN L, CHEN S, et al. The administration of Escherichia coli Nissle 1917 ameliorates irinotecan-induced intestinal barrier dysfunction and gut microbial dysbiosis in mice.Life sciences, 2019,231:116529.

[133]  LIU T, WU Y, WANG L, et al. A More Robust Gut Microbiota in Calorie-Restricted Mice Is Associated with Attenuated Intestinal Injury Caused by the Chemotherapy Drug Cyclophosphamide.mBio,2019,10(2): e02903-18

[134]  Reyna-Figueroa J, Barrón-Calvillo E, García-Parra C, et al. Probiotic Supplementation Decreases Chemotherapy-induced Gastrointestinal Side Effects in Patients With Acute Leukemia.J J Pediatr Hematol Oncol, 2019,41(6):468-472.

[135]  ZHANG S, YANG Y, WENG W, et al. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer.J Exp Clin Cancer Res, 2019, 38(1): 14.

[136]  Flynn M, Dooley J. The microbiome of the nasopharynx. J Med Microbiol,2021,70(6) :001368

[137]  Akimbekov NS, Digel I, Yerezhepov AY, et al. Nutritional factors influencing microbiota-mediated colonization resistance of the oral cavity: A literature review. Front Nutr,2022,9:1029324.

[138]  Freire M, Nelson KE, Edlund A. The Oral Host-Microbial Interactome: An Ecological Chronometer of Health. Trends Microbiol,2021,29(6): 551-561.

[139]  Kitamoto S, Nagao-Kitamoto H, Jiao Y, et al. The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis. Cell,2020,182(2): 447-462.e14.

[140]  Zheng W, Zhao S, Yin Y, et al. High-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome. Science,2022,376(6597): eabm1483.

[141]  Khoruts A,Staley C,Sadowsky MJ.Faecal microbiota transplantation for Clostridioides difficile:mechanisms and pharmacology.Nat Rev Gastroenterol Hepatol,2021,18(1):67-80.

[142]  Liu X,Tong X,Zou Y,et al.Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome.Nature Genetics,2022,54(1):52-61.

[143]  Zitvogel L,Ma Y,Raoult D,et al.The microbiome in cancer immunotherapy:Diagnostic tools and therapeutic strategies.Science,2018,359(6382):1366-1370.

[144]  Innes AJ, Mullish BH, Fernando F, et al. Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality. Bone Marrow Transplant, 2017, 52(10): 1452-1454.

[145]  Biliński J, Grzesiowski P, Muszyński J, et al. Fecal microbiota

[146]  Kaito S, Toya T, Yoshifuji K, et al. Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease. Blood Adv, 2018, 2(22): 3097-3101.

[147]  Liu Y, Zhao Y, Qi J,et al. Fecal microbiota transplantation combined with ruxolitinib as a salvage treatment for intestinal steroid-refractory acute GVHD. Exp Hematol Oncol, 2022, 11(1):96.

[148]  Wang J, Liang J, He M,et al.Chinese expert consensus on intestinal microecology and management of digestive tract complications related to tumor treatment (version 2022). J Cancer Res Ther,2022,18(7):1835-1844.