切换至 "中华医学电子期刊资源库"
高级检索
中华肥胖与代谢病电子杂志

中华肥胖与代谢病电子杂志 ›› 2024, Vol. 10 ›› Issue (02) : 138 -144. doi: 10.3877/cma.j.issn.2095-9605.2024.02.011

青年专家论坛

粪菌移植治疗肥胖及代谢相关脂肪性肝病的临床研究进展
冯婷1, 叶俊钊2,†()   
  1. 1. 510080　广州，广东药科大学附属第一医院消化内科
    2. 中山大学附属第一医院消化内科
  • 收稿日期:2024-03-08 出版日期:2024-05-30
  • 通信作者: 叶俊钊

Research progress on fecal microbiota transplantation in the treatment of obesity and metabolic dysfunction-associated steatotic liver disease

Ting Feng1, Junzhao Ye2,†()   

  1. 1. Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University
    2. Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
  • Received:2024-03-08 Published:2024-05-30
  • Corresponding author: Junzhao Ye
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

冯婷, 叶俊钊. 粪菌移植治疗肥胖及代谢相关脂肪性肝病的临床研究进展[J]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 138-144.

Ting Feng, Junzhao Ye. Research progress on fecal microbiota transplantation in the treatment of obesity and metabolic dysfunction-associated steatotic liver disease[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(02): 138-144.

肠道微生态紊乱深度参与肥胖及代谢相关脂肪性肝病的发生发展。粪菌移植作为一种新型肠道菌群调节及治疗手段，其在肥胖及代谢相关脂肪性肝病治疗中的应用备受关注，近年国内外相继开展大量临床研究进行积极深入探索。粪菌移植在肥胖治疗中对体重的直接疗效十分有限，对相关代谢紊乱的缓解作用仍不明确，但其在辅助减重术后体重管理具有前景，对于肥胖及代谢相关脂肪性肝病瘦人亚型脂肪含量改善可能有积极帮助。本文就粪菌移植在肥胖及代谢相关脂肪性肝病的治疗临床证据进行总结及阐述。

关键词: 肥胖, 肥胖及代谢相关脂肪性肝病, 粪菌移植, 疗效

Gut microbiota dysbiosis plays a significant role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Fecal microbiota transplantation (FMT), as a novel approach for gut microbiota modulation and therapy, has garnered considerable attention in the treatment of obesity and MASLD. Numerous clinical studies have been conducted in recent years both domestically and internationally, actively exploring its applications. FMT has shown limited direct efficacy in weight reduction for treating obesity and its effects on alleviating associated metabolic disorders remain unclear. However, it holds promise in weight management following bariatric surgery and may offer positive outcomes in improving hepatic steatosis among lean obese individuals and with MASLD subtypes. This paper summarizes and discusses the clinical evidence of FMT in the treatment of obesity and MASLD.

Key words: Obesity, Metabolic dysfunction-associated steatotic liver disease, Fecal microbiota transplantation, Therapeutic effects
图1 粪菌移植的技术流程及对肥胖及MASLD患者肠道菌群的影响
表1 肥胖患者FMT治疗后疗效分析
作者，年份 国家 研究对象 研究分组 研究时间 观察指标 临床有效性 代谢物改变 肠道菌群改变
Hu D et al. [23] 2023 中国 肥胖 Meta   HOMA-IR、HbA1c水平、体重、BMI HOMA-IR等指标均明显降低    
Zecheng L et al. [24] 2023 中国 肥胖 Meta   HOMA-IR、血压、血脂、空腹血糖、CRP、乙酸、膳食热量摄入 HOMA-IR等指标均明显降低    
Ghorbani Y et al. [25] 2023 加拿大 肥胖 RCT，异体FMT vs.自体FMT FMT治疗后1月 HOMA-IR、HbA1c水平、血脂谱、体重、肠道激素、内毒素、食欲测量、肠道菌群、血清/粪便代谢物、生活质量、焦虑和抑郁评分 HOMA-IR等临床指标均无统计学意义 增加：粪便中的吲哚乙酸和丁烯基肉
减少：血清喹啶酮		 增加：腐球菌属、双歧杆菌属、拟杆菌属和玫瑰布里菌属
减少：链球菌属
        FMT治疗后3月       增加：拟杆菌属和布劳提菌属
Lahtinen P et al. [26] 2022 芬兰 肥胖 RCT，异体FMT vs自体FMT FMT治疗后6、18月 体重下降比例 体重下降比例无统计学意义    
Rinott E et al. [27] 2021 & Kamer O et al. [28] 2023 以色列 肥胖 RCT，饮食调节自体FMT胶囊vs.安慰剂 FMT治疗后8月 体重回升、胃肠道症状、腰围、血糖状态、肠道菌群变化 体重回升、腰围增加、胰岛素水平反弹均减缓   增加：马赛拟杆菌和帕拉普氏菌属
表2 MASLD患者FMT治疗后疗效分析
作者,年份 国家 研究对象 研究分组 研究时间 观察指标 临床有效性 肠道菌群改变
Xue L et al. [29] 2022 中国 MASLD RCT，异体FMT vs.口服益生菌 治疗1月后 脂肪衰减系数 瘦人MASLD的平均脂肪衰减系数降至正常水平，肥胖MASLD的脂肪衰减系数未见明显变化 瘦人MASLD：
增加：塞氏单甲酸杆菌目、威隆氏菌科、普雷沃特拉氏菌属、真杆菌属、罗斯贝里亚菌属、瘤胃链球菌组
减少：放线菌门、硫还原弧菌目、拟杆菌属
肥胖MASLD：
增加：瘤胃链球菌组、普雷沃特拉氏菌属、乳酸杆菌丰度
减少：Rikenella RC9肠道菌群、另枝菌属
Stols-Gonçalves D et al. [30] 2021 荷兰 MASLD RCT，素食为主的异体FMT vs.自体FMT 第24周 肝活检相关评分，谷氨酰转肽酶 炎症坏死评分出现了临界差异，总的脂肪肝活动度评分及纤维化程度均未见差异，异源性FMT组的谷氨酰转肽酶水平下降  
Craven L et al.[31] 2020 加拿大和英国 MASLD RCT，异体FMT vs.自体FMT FMT治疗后6个月 HOMA-IR，肝脏PDFF，肠道通透性 FMT未能改善以HOMA-IR或肝脏PDFF测量的IR，有潜力减少小肠通透性  
Qiu XX et al. [32] 2024 中国 MASLD Meta   血脂、转氨酶、HOMA-IR、BMI HOMA-IR等临床指标均无统计学意义  
Yu EW et al. [34] 2020 伊朗 MASLD Meta   糖化血红蛋白、胰岛素水平、血脂、血糖、人体测量指标、肠道菌群 FMT可减少糖化血红蛋白、胰岛素水平，增加HDL水平 增加：梭杆菌属、坎氏肠球菌、无氧链球菌属、厚壁梭菌和原肠球菌属，拟杆菌和普雷沃氏菌属以及双歧杆菌属
减少：梭杆菌属和瘤胃球菌属
[1]
Zhou X, Zhang X, Yu J. Gut mycobiome in metabolic diseases: mechanisms and clinical implication [J]. Biomed J, 2023: 100625.
[2]
Jayachandran M, Qu S. Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies [J]. Rev Endocr Metab Disord. 2023, 24(6): 1189-1204.
[3]
Quesada-Vázquez S, Castells-Nobau A, Latorre J, et\ al. Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity [J]. Cell Rep Med, 2023, 4(12): 101341.
[4]
Schmidt TSB, Li SS, Maistrenko OM, et al. Drivers and determinants of strain dynamics following fecal microbiota transplantation [J]. Nat Med, 2022, 28(9): 1902-1912.
[5]
van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile [J]. N Engl J Med, 2013, 368(5): 407-415.
[6]
Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recur rent Clostridium difficile infection: a randomized trial [J]. Ann Intern Med, 2016, 165(9): 609-616.
[7]
Nicholson MR, Mitchell PD, Alexander E, et al. Efficacy of fecal microbiota transplantation for Clostridium difficile infec tion in children [J]. Clin Gastroenterol Hepatol, 2020, 18(3): 612-619.
[8]
Peery AF, Kelly CR, Kao D, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases [J]. Gastroenterology, 2024, 166(3): 409-434.
[9]
Quraishi MN, Widlak M, Bhala N, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection [J]. Aliment Pharmacol Ther, 2017, 46(5): 479-493.
[10]
Leong KSW, Jayasinghe TN, Wilson BC, et al. Effects of fecal microbiome transfer in adolescents with obesity: the Gut Bugs Randomized Controlled Trial [J]. JAMA Netw Open, 2020, 3(12): e2030415.
[11]
Craven L, Rahman A, Nair Parvathy S, et al. Allogenic fecal microbiota transplantation in patients with nonalcoholic fatty liver disease improves abnormal small intestinal permeability: A randomized control trial [J]. Am J Gastroenterol. 2020, 115(7): 1055-1065.
[12]
Witjes JJ, Smits LP, Pekmez CT, et al. Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis [J]. Hepatol Commun, 2020, 4(11): 1578-1590.
[13]
Zhou X, Chen R, Cai Y, et al. Fecal microbiota transplantation: a prospective treatment for type 2 diabetes mellitus [J]. Diabetes Metab Syndr Obes, 2024, 17: 647-659.
[14]
Zhong HJ, Zeng HL, Cai YL, et al. Washed microbiota transplantation lowers blood pressure in patients with hypertension [J]. Front Cell Infect Microbiol, 2021, 11: 679624.
[15]
Liang F, Lu X, Deng Z, et al. Effect of washed microbiota transplantation on patients with dyslipidemia in South China [J]. Front Endocrinol (Lausanne), 2022, 13: 827107
[16]
Xie WR, Yang XY, Deng ZH, et al. Effects of Washed Microbiota Transplantation on Serum Uric Acid Levels, Symptoms, and Intestinal Barrier Function in Patients with Acute and Recurrent Gout: A Pilot Study [J]. Dig Dis, 2022, 40(5): 684-690.
[17]
Yu Y, Wang W, Zhang F. The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome [J]. Adv Sci (Weinh), 2023, 10(35): e2301097.
[18]
Shi Q, editors. Nanjing consensus on methodology of washed microbiota transplantation [J]. Chin Med J (Engl), 2020, 133(19): 2330-2332.
[19]
Zhang T, Lu G, Zhao Z, et al. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening [J]. Protein Cell, 2020, 11(4): 251-266.
[20]
Zhang T, Lu G, Zhao Z, et al. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening [J]. Protein Cell, 2020, 11(4): 251-266.
[21]
Youngster I, Eshel A, Geva M, et al. Fecal microbiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease: a pilot study [J]. Bone Marrow Transplant, 2024, 59(3): 409-416.
[22]
Stefansson M, Bladh O, Flink O, et al. Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial [J]. PLoS One, 2023, 18(9): e0292132.
[23]
Hu D, Zhao J, Zhang H, et al[. Fecal Microbiota Transplantation for Weight and Glycemic Control of Obesity as Well as the Associated Metabolic Diseases: Meta-Analysis and Comprehensive Assessment [J]. Life (Basel), 2023, 13(7): 1488.
[24]
Zecheng L, Donghai L, Runchuan G, et al. Fecal microbiota transplantation in obesity metabolism: A meta-analysis and systematic review [J]. Diabetes Res Clin Pract, 2023, 202: 110803.
[25]
Ghorbani Y, Schwenger KJP, Sharma D, et al. Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial [J]. Diabetes Obes Metab, 2023, 25(2): 479-490.
[26]
Lahtinen P, Juuti A, Luostarinen M, et al. Effectiveness of fecal microbiota transplantation for weight loss in patients with obesity undergoing bariatric surgery: a randomized clinical trial [J]. JAMA Netw Open, 2022, 5(12): e2247226.
[27]
Rinott E, Youngster I, Yaskolka Meir A, et al. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain [J]. Gastroenterology, 2021, 160(1): 158-173. e10.
[28]
Kamer O, Rinott E, Tsaban G, et al. Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial [J]. Gut Microbes, 2023, 15(2): 2264457.
[29]
Xue L, Deng Z, Luo W, et al. Effect of fecal microbiota transplantation on non-alcoholic fatty liver disease: a randomized clinical trial [J]. Front Cell Infect Microbiol, 2022, 12: 759306.
[30]
Stols-Gonçalves D, Mak AL, Madsen MS, et al. Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach [J]. Gut Microbes, 202, 15(1): 2223330.
[31]
Craven L, Rahman A, Nair Parvathy S, et al. Allogenic fecal microbiota transplantation in patients with nonalcoholic fatty liver disease improves abnormal small intestinal permeability: a randomized control trial [J]. Am J Gastroenterol, 2020, 115(7): 1055-1065.
[32]
Qiu XX, Cheng SL, Liu YH, et al. Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect [J]. World J Gastroenterol, 2024, 30(8): 833-842.
[33]
Pakmehr A, Mousavi SM, Ejtahed HS, et al. The Effect of fecal microbiota transplantation on cardiometabolic risk factors: a systematic review and meta-analysis[J]. Clin Ther, 2024, 46(2): e87-e100.
[34]
Yu EW, Gao L, Stastka P, et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial [J]. PLoS Med, 2020, 17(3): e1003051.
[35]
Ding D, Yong H, You N, et al. Prospective study reveals host microbial determinants of clinical response to fecal microbiota transplant therapy in type 2 diabetes patients [J]. Front Cell Infect Microbiol, 2022, 12: 820367.
[36]
Kamal FD, Dagar M, Reza T, et al. Beyond diet and exercise: the impact of gut microbiota on control of obesity [J]. Cureus, 2023, 15(11): e49339.
[1] 陈镁仪, 李伊尧, 张梦圆, 许杰, 马若凡, 李登, 顾菁. 图示化自主髋关节功能评分系统的应用研究[J]. 中华关节外科杂志(电子版), 2024, 18(03): 320-328.
[2] 苏永涛, 王春雷, 徐广琪, 关中正, 焦伟, 隋颖. 胫骨骨膜牵张术联合富血小板血浆对治疗糖尿病足溃疡的疗效观察[J]. 中华损伤与修复杂志(电子版), 2024, 19(03): 238-244.
[3] 李猛, 姜腊, 董磊, 吴情, 贾犇黎. 腹腔镜胃袖状切除术治疗肥胖合并2型糖尿病及脂肪胰的临床研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 554-557.
[4] 吉顺富, 汤晓燕, 徐进. 腹腔镜近端胃癌根治术中拓展胃后间隙在肥胖患者中的应用研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 393-396.
[5] 谢丽春, 欧庆芬, 张秋萍, 叶升. 简化和标准肝脏MRI方案在结直肠癌肝转移患者随访中的临床应用[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 434-437.
[6] 杨波, 胡旭, 何金艳, 谢铭. 腹腔镜袖状胃切除术管胃固定研究现状[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 452-455.
[7] 危用洋, 黄俊甫, 辛万鹏, 易思清, 涂书举, 方康, 李勇, 肖卫东. 三种术式治疗胰腺颈体部良性或低度恶性肿瘤的临床疗效分析[J]. 中华肝脏外科手术学电子杂志, 2024, 13(04): 515-519.
[8] 王凯飞, 牟怡平, 李晓辉, 王瑞涛, 侯惠莲, 张月浪. 原发性肝平滑肌肉瘤临床病理特征及疗效分析[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 357-362.
[9] 马欢欢, 马晨辉, 邓小博, 王博方, 何普毅, 王云鹏, 许博, 俞荣, 王娜, 陈昊. 肝癌实体瘤治疗疗效评价系统的研究进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 377-383.
[10] 杨智義, 赵成俊, 胡欣芫, 潘佰猛, 张秋雨, 张挽乾, 曹芮, 张灵强. 外周血cfDNA液体活检技术在肝棘球蚴病诊治中的应用进展[J]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 389-393.
[11] 黄福秀, 张宁宁, 李晨阳, 李淑玲, 陈超. 单纯电切、单纯电凝与电凝电切术对扁平肠息肉疗效及不良事件发生率的影响[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 310-314.
[12] 陶金华, 陈珊珊, 陈晓四. 阿帕替尼联合替吉奥治疗晚期食管癌的疗效与安全性影响因素评价[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 325-329.
[13] 唐小久, 胡曼, 许必君, 肖亚. 肥胖合并胃食管反流病患者严重程度与其焦虑抑郁及营养状态的相关性研究[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 360-364.
[14] 周敏, 张仁清, 卢贤红. 秋泻灵联合双歧杆菌三联活菌散对轮状病毒腹泻患儿免疫功能、心肌酶和C反应蛋白的影响[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 365-368.
[15] 袁捷, 乔钰琪, 李彦冬. 二甲双胍、来曲唑联合地屈孕酮治疗多囊卵巢综合征合并不孕症的效果评价[J]. 中华临床医师杂志(电子版), 2024, 18(04): 343-347.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号