Groenewegen Bas, Ruissen Merel M, Crossette Emily, Menon Rajita, Prince Amanda L, Norman Jason M, Ballieux Bart E P B, Lamb Hildo J, Terveer Elisabeth M, Keller Josbert J, Tushuizen Maarten E
Netherlands Donor Feces Bank, Leiden University Center of Infectious Diseases (LUCID) Medical Microbiology and Infection Prevention, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Department of Gastroenterology and Hepatology, LUMC, Leiden, The Netherlands.
Gut Microbes. 2025 Dec;17(1):2541035. doi: 10.1080/19490976.2025.2541035. Epub 2025 Aug 4.
The gut microbiota is increasingly considered a contributory factor in metabolic dysfunction-associated steatotic liver disease (MASLD). This double-blind RCT evaluated the effect of three consecutive fecal microbiota transplantations (FMT) on hepatic steatosis in MASLD. Twenty patients with MASLD were randomized (1:1) to receive allogeneic or autologous FMTs at weeks 0, 3, and 6, with follow-up through week 12. FMT material was derived from two donors. We assessed changes in hepatic steatosis (magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF)), glucose tolerance (oral glucose tolerance test), liver biochemistry, and gut microbiota composition/engraftment. Change in MRI-PDFF from baseline to week 12 was notsignificantly different between groups ( = 0.50). Liver biochemistry and glucose tolerance also showed no significant overall changes. Patients' stool microbiota exhibited high baseline alpha diversity and similar composition across treatment groups, diverging by week 12 ( = 0.02). Two microbial taxa belonging to the families and were associated with triglyceride levels after FMT. No further microbiota signatures were associated with FMT-treatment or response. Donor microbiota engraftment appeared donor-specific, but not treatment- or response-specific. In conclusion, FMT did not significantly affect hepatic steatosis, glucose tolerance, liver biochemistry, or gut microbiota signatures. Future studies should consider including patients with low microbiota diversity. Dutch Trial Register: NL-OMON48776; Central Committee on Research Involving Human Subjects: NL66705.058.18; Clinicaltrials.gov: NCT04465032.
肠道微生物群越来越被认为是代谢功能障碍相关脂肪性肝病（MASLD）的一个促成因素。这项双盲随机对照试验评估了连续三次粪便微生物群移植（FMT）对MASLD患者肝脂肪变性的影响。20例MASLD患者被随机分为两组（1:1），在第0、3和6周接受异体或自体FMT，并随访至第12周。FMT材料来自两名供体。我们评估了肝脂肪变性（磁共振成像衍生的质子密度脂肪分数（MRI-PDFF））、葡萄糖耐量（口服葡萄糖耐量试验）、肝脏生化指标和肠道微生物群组成/植入的变化。两组从基线到第12周MRI-PDFF的变化无显著差异（=0.50）。肝脏生化指标和葡萄糖耐量也没有显著的总体变化。患者粪便微生物群在基线时表现出较高的α多样性，各治疗组之间的组成相似，但在第12周时出现分化（=0.02）。两个属于和科的微生物分类群与FMT后的甘油三酯水平相关。没有进一步的微生物群特征与FMT治疗或反应相关。供体微生物群植入似乎具有供体特异性，但不具有治疗或反应特异性。总之，FMT对肝脂肪变性、葡萄糖耐量、肝脏生化指标或肠道微生物群特征没有显著影响。未来的研究应考虑纳入微生物群多样性低的患者。荷兰试验注册编号：NL-OMON48776；人类研究中央委员会编号：NL66705.058.18；Clinicaltrials.gov编号：NCT04465032。
