摘要

       抗生素耐药性导致肝硬化的不良结局。粪便微生物群移植 (FMT) 与非肝硬化患者的抗生素耐药基因 (ARG) 负担减少有关；然而，对肝硬化的影响尚不清楚。我们旨在研究胶囊和灌肠 FMT 对粪便样本中 ARG 丰度的影响，粪便样本是在两项已发表的 FMT 试验中收集的，这些试验是在肝硬化患者使用利福昔明、乳果糖和质子泵抑制剂进行的。使用宏基因组学鉴定 ARG，并根据综合抗生素耐药性数据库进行映射。研究了组内/组间 ARG 丰度的变化。胶囊 FMT 试验涉及一次性 FMT 或安慰剂胶囊给药，并在基线和干预后第 4 周收集粪便。抗生素 + 灌肠 FMT 包括术前抗生素，然后是 FMT 灌肠与标准护理 (SOC)。在基线、抗生素后和干预后第 7/15 天收集粪便。两项试验均包括 20 名患者。没有与 FMT 相关的安全/感染信号。在胶囊试验中，β-内酰胺酶 (OXY/LEN) 表达在 FMT 后与基线相比降低。与安慰剂相比，FMT 后患者的万古霉素 (VanH)、β-内酰胺酶 (ACT) 和利福霉素 ARG 丰度较低；后者与认知改善有关。在接受安慰剂治疗的患者中没有发现任何变化。在第 7 天与基线相比，抗生素后抗生素+灌肠试验中，万古霉素和 β-内酰胺酶 ARG 增加，在第 15 天下降。然而，喹诺酮类耐药性在第 15 天与基线相比增加。在 SOC 和 FMT 之间，第 7 天的 ARG（CfxA β-内酰胺酶、VanW 和 VanX）在第 15 天（cepA β-内酰胺酶、VanW）持续下降。 SOC 组内未见变化。结论：尽管给药途径和干预前抗生素存在差异，但我们发现，与失代偿期肝硬化的 FMT 前基线和非 FMT 组相比，FMT 后 ARG 丰度大大降低。

       Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.

https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep4.1639