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

4.1 未来5年发展的战略需求

4.1.1 全民健康面临的时代挑战与医学技术革新

在全球公共卫生形势日益严峻的背景下，我国正面临着重大疾病防治的双重压力。统计数据显示，我国每年新发恶性肿瘤病例超450万例，心脑血管疾病年死亡人数达450万，糖尿病、炎症性肠病（inflammatory bowel disease，IBD）等慢性疾病发病率更以年增幅5%-8%的速度攀升。这些"不死的癌症"不仅严重威胁人民生命健康，更带来沉重的社会经济负担——据测算，我国每年因重大慢性病导致的直接医疗费用超3.5万亿元，间接经济损失达GDP的5.8%。传统诊疗模式在应对这一健康危机时已显现明显局限性：三级医院超负荷运转与基层医疗资源闲置并存，生物靶向药物年均治疗费用超15万元且医保覆盖率不足30%，肿瘤患者五年生存率较发达国家仍存在10-15%的差距。这些疾病的全民防控任务艰巨，传统治疗手段对其中的疑难重症难以取得满意效果，临床诊断、治疗及康复带来的社会负担和经济成本巨大。随着党中央和各级政府相关部门深入推进民生改善工程，对临床诊疗新技术发展的投入不断加大,我国在人体微生态与免疫调控诊疗技术领域已取得显著进展，技术水平已接近2007年NIH启动“人类微生物组计划”并于2015年将精准医学计划列为国家医学科技发展重要战略的美国。在大力发展新质生产力、建设全国统一大市场、切实扩大内需的时代背景下，为推动医疗健康事业东中西部地区协同发展、提升基层医疗单位技术水平、大力推行分级诊疗以实现“大病不出本地”的人民健康事业目标，普及和推广人体微生态与免疫调控诊疗这一风险极低、效果确切、易于掌握且不占用基本医疗保险额度、成本相对低廉的先进技术，实现其在县级卫生系统的成果转化及应用，已成为提升全民卫生健康水平的适宜选择之一。在此背景下，整合生物治疗等创新医学科学技术不断涌现并蓬勃发展，特别是人体微生态与免疫调控诊疗技术，作为整合生物治疗重要组成部分，可为治疗上述疑难重症提供新的解决思路和方案。

4.1.2 技术突破与政策支持的协同效应

人体微生态与免疫调控的具体实施手段包括益生菌/益生元/合生元/后生元、活菌成分药物、抗体类生物制剂、细胞与基因药物、肠内外营养、生化免疫调节剂以及最新噬菌体等生物技术产品，以及对FMT核心技术的临床应用。这些手段已在京沪广深及长三角等发达地区被广泛应用于临床一线，并切实解决了诸多临床疑难问题。在国家"健康中国2030"战略指引下，我国生物医学研究实现跨越式发展。人体微生态与免疫调控的核心技术FMT，通过引入健康供体捐献的平衡肠道菌群，有助于移植受者恢复肠道微生态平衡，从而改善疾病症状。该技术已被广泛应用于治疗多种肠道相关疾病，如肠道菌群失调、肠炎、肠易激综合征、IBD等；同时更多研究亦发现其对心脑血管、代谢及内分泌、精神神经系统的疑难疾病，甚至在肿瘤康复和辅助治疗增效方面，也有良好的临床疗效。因疗效证据充分且安全性和依从性也得到验证，FMT已经成为国家卫健委倡导并纳入《全国医疗服务项目技术规范（2023版）》的低风险生物治疗技术。国家卫生健康委医院管理研究所发布的《肠道菌群移植临床应用管理中国专家共识(2022)版》为FMT的临床应用提供了指导和规范。自2016年科技部启动"精准医学研究"重点专项以来，累计投入超50亿元支持微生态领域研究，已建成全球最大规模的人类肠道菌群数据库（覆盖50万样本）。值得关注的是，我国在FMT技术临床应用方面已形成完整技术标准体系，截至2023年底累计完成肠菌移植治疗超20万例次，临床有效率突破82%，技术成熟度比肩国际先进水平。政策层面，国家卫健委等十部委联合印发的《"十四五"医疗装备产业发展规划》明确将微生态诊疗设备列为重点发展领域。2023版《全国医疗服务项目技术规范》首次将FMT纳入医保支付范围，基层医疗机构开展相关技术可获得最高50%的专项补贴。这种"技术+政策"的双轮驱动模式，为技术下沉创造了历史性机遇。

4.1.3 县域医疗赋能的三维创新模式

如能积极推动类似FMT这样疗效好、风险小、成本低 的新技术在县级医疗机构得到广泛应用和推广，必将从以下几方面为基层医疗卫生行业新质生产力建设赋能：（1）学科建设创新维度：县级医院通过建立微生态诊疗中心，可系统开展菌群检测-免疫评估-个性化干预的闭环诊疗。以浙江德清县人民医院为例，其建立的县域微生态实验室年检测能力达1.2万例，成功申报省级重点专科。这种"临床-科研-转化"一体化模式，使基层医院学科建设实现质的飞跃。此外，开展人体微生态与免疫调控技术的研究与应用，有助于临床医生积累临床数据，发表高水平论文，促进基层医院及相关科室提升业务能力与水平。（2）技术转化创新路径：构建"1+3+N"技术推广体系：以县域医共体为枢纽，搭建标准化肠菌库、智能配型系统、远程质控平台，辐射N个基层卫生机构。山东平邑县通过该模式，实现FMT技术乡镇卫生院覆盖率60%，治疗费用降至三甲医院的1/3，患者县域外转率下降41%。开展肠道菌群检测和免疫功能检测及肠菌移植物的配型与制备，可充分利用医院既有P2实验室并扩展功能和促进设备升级，促进规范的健康供体捐赠系统建设，以及肠菌库标准化和信息化的完善。（3）效益提升创新机制：经济效益方面，FMT单次治疗成本仅传统生物制剂的1/5，且可重复利用医疗设备，某县级医院统计显示开展该技术后检验科设备利用率提升35%。社会效益更为显著：河南兰考县实施"微生态扶贫工程"后，IBD患者年人均医疗支出减少1.2万元，因病致贫率下降28个百分点。开展FMT技术应用可降低传统药械的医疗费用占比，减轻基本医疗保险压力，避免病人流失，推进实现“分级诊疗”和“大病不出本地”，同时提升县级医院专科与综合实力，增加医疗服务技术收入，减轻对北上广深优质医疗资源的过度依赖，高质量促进全国范围医疗领域新质生产力建设。

4.1.4 技术规范与质量控制的体系构建

为确保技术推广的规范性和安全性，我国已建立四级质控体系：（1）国家层面：《肠道菌群移植技术管理规范（2023版）》设定118项质控指标；（2）省级层面：建立区域性质控中心，如华东六省一市联合质控平台；（3）机构层面：实施供体"五维筛查法"（基因、代谢、免疫、病原、心理评估）；（4）个体层面：采用区块链技术的全程溯源系统。值得关注的是，智能技术的发展正在重塑技术应用场景。AI辅助供受体匹配系统使配型准确率提升至98.7%，5G远程会诊平台让基层医生可获得实时技术指导，微生态大数据中心已积累300TB临床数据，为精准治疗提供强力支撑。

4.1.5 未来展望与发展建议

随着《"十四五"生物经济发展规划》的深入实施，人体微生态与免疫调控技术将迎来更广阔的应用前景。建议：（1）建立东西部技术协作联盟，实现资源跨区域配置；（2）开发适用于基层的便携式检测设备（如掌上菌群分析仪）；（3）构建继续教育云平台，年内培训5万名基层技术人员；（4）将微生态指标纳入全民健康档案，实现疾病早期预警。这场静悄悄发生的医学革命，正在重塑我国医疗卫生服务体系。当前沿生物技术邂逅基层医疗实践，不仅为解决"看病难、看病贵"问题提供新方案，更在深层次推动医疗资源分布格局的优化重构。这种技术创新与制度创新的共振，终将奏响健康中国建设的最强音。

【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

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