粪便微生物移植在治疗类固醇难治性胃肠道移植物抗宿主病中的应用

Abstract

Abstract Objective To assess the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of gastrointestinal graft-versus-host disease (GI-GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods 25 patients with steroid-refractory GI-GvHD were enrolled in this study from 2017-2023, 1-3 doses of 4.5-8.0 U/dose fecal microbiota were infused via nasal-jejunal tube or fecal capsules. Then, the curative effect and side effects after FMT were observed. Results 25 steroid-refractory GI-GvHD patients were composed of 12 males and 13 females, mean age of 34.8 years.21 patients received haplo-HSCT, 4 received MSD-HSCT. ATG + CsA + MMF + short-term MTX were applied to prevent GvHD disease. Among them, 7 patients accompanied with liver GvHD and 11 with skin GvHD. The average onset time of GI-GvHD was +69.3d after HSCT. All patients were evaluated as grade IV GI-GvHD, and the abdominal pain score was 4 points. FMT via nasal-jejunal tube wastaken in 12 patients and the rest were fecal capsules. Among the patients, 12 underwent one session of FMT, 10 underwent two sessions, and 3 underwent three sessions. Following FMT, out of the 25 patients, 21 achieved complete remission (CR) (84.0%), with symptoms such as abdominal pain, diarrhea, and bloody stools resolved. Partial remission (PR) was observed in 1 patient (4.0%), whose diarrhea volume and frequency did not meet the criteria for CR. Progressive disease (PD) occurred in 3 patients (12.0%), presenting with persistent bloody stools, cramping abdominal pain. We measured the peripheral blood Treg cell counts in 16 patients who achieved CR. Prior to FMT, these patients exhibited low peripheral blood Treg cell levels. Post-FMT, their Treg cell counts significantly increased (P< 0.01), which correlated positively with the improvement in GI-GvHD symptoms. We performed 16s rRNA sequencing of the gut microbiota in 16 patients during both the onset of GI-GvHD and after achieving CRof GI-GvHD. The results demonstrated that gut microbiota diversity was significantly reduced during active GI-GvHD. Following FMT and attainment of CR, the diversity of the gut microbiota showed marked improvement (P< 0.01). Inthe 25 patients, 3 experienced PD, presenting with nausea, vomiting, and persistent bloody stools. These symptoms showed no improvement despite symptomatic treatment. Additionally, 6 patients who achieved CRexhibited nausea and vomiting, which were effectively controlled with symptomatic treatment. None of the patients developed FMT-related infections. ConclusionFecal microbiota transplantation was effective and safe for steroid-refractory GI-GvHD patients after allo-HSCT. Key wordsAllogeneic hematopoietic stem cell transplantation; Steroid-refractory gastrointestinal graft-versus-host disease；Fecal microbiota transplantation