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

doi:10.3877/cma.j.issn.2095-9605.2024.02.011

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

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

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

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