粪菌移植治疗异基因造血干细胞移植后糖皮质激素耐药胃肠道急性移植物抗宿主病19例临床研究

OBJECTIVE: To investigate the clinical efficacy of fecal microbiota transplantation（FMT）for treating steroid-refractory gastrointestinal acute graft-versus-host disease（GI-aGVHD）. METHODS: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation（allo-HSCT）in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment（the FMT group）and 10 patients did not（the control group）. The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. RESULTS: ① Complete remission of clinical symptoms after FMT was achieved by 13（68.4％）patients and 2（20.0％）controls, with a statistically significant difference（P<0.05）. Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells（Treg）, and CD4(+)/CD8(+) cells increased（all P<0.05）. The interleukin（IL）-6 concentration in the FMT group was lower than that in the control group［4.15（1.91–5.71）ng/L vs 6.82（2.40–8.91）ng/L, P＝0.040］, and the IL-10 concentration in the FMT group was higher than that in the control group［12.11（5.69–20.36）ng/L vs 7.51（4.10–9.58）ng/L, P＝0.024］. Islet-derived protein 3α（REG3α）was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment［30.70（10.50–105.00）µg/L vs 74.35（33.50–139.50）µg/L, P＝0.021］. CONCLUSION: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.