Gastroenterology, Hepatology, and NutritionVirginia Commonwealth University and Central Virginia Veterans Healthcare SystemRichmondVAUSA.
Microbiome Analysis CenterGeorge Mason UniversityManassasVAUSA.
Hepatol Commun. 2020 Nov 21;5(2):258-271. doi: 10.1002/hep4.1639. eCollection 2021 Feb.
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. 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.
抗生素耐药性导致肝硬化患者预后不良。粪便微生物群移植（FMT）与无肝硬化患者抗生素耐药基因（ARG）负担减少相关；然而，其在肝硬化中的影响尚不清楚。我们旨在研究胶囊和灌肠 FMT 对肝硬化患者接受利福昔明、乳果糖和质子泵抑制剂治疗期间收集的粪便样本中 ARG 丰度的影响，这些患者之前已经参与了两项关于 FMT 的临床试验。使用宏基因组学鉴定 ARGs，并将其与综合抗生素耐药数据库进行比对。研究了组内/组间 ARG 丰度的变化。胶囊 FMT 试验包括单次 FMT 或安慰剂胶囊给药，在干预后第 4 周收集粪便样本。抗生素+灌肠 FMT 包括术前抗生素治疗，然后进行 FMT 灌肠，与标准护理（SOC）相比。在基线、使用抗生素后和干预后第 7/15 天收集粪便样本。这两项试验各纳入了 20 名患者。FMT 没有与安全性/感染相关的信号。在胶囊试验中，与基线相比，使用 FMT 后β-内酰胺酶（OXY/LEN）表达降低。与安慰剂相比，接受 FMT 的患者的万古霉素（VanH）、β-内酰胺酶（ACT）和 rifamycin ARG 丰度较低；后者与认知改善相关。接受安慰剂的患者没有观察到变化。在抗生素+灌肠试验中，与基线相比，第 7 天的万古霉素和β-内酰胺酶 ARG 增加，第 15 天减少。然而，与基线相比，第 15 天的喹诺酮类耐药性增加。与 SOC 和 FMT 相比，第 7 天的 ARG（CfxA 内酰胺酶、VanW 和 VanX）总体较低，第 15 天仍保持较低水平（cepA 内酰胺酶、VanW）。SOC 组内没有观察到变化。尽管给药途径和术前抗生素不同，但我们发现与 FMT 前基线和非 FMT 组相比，在失代偿性肝硬化中，FMT 后 ARG 丰度在很大程度上降低。
