Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.
Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.
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DOI：
10.1002/hep4.1639
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发表时间：
2021-03
影响因子：
5.1
通讯作者：
Gillevet PM
中科院分区：
文献类型：
--
作者：
Bajaj JS;Shamsaddini A;Fagan A;Sterling RK;Gavis E;Khoruts A;Fuchs M;Lee H;Sikaroodi M;Gillevet PM
粪便移植与失代偿期肝硬化患者抗生素耐药基因表达减少相关无论术前是否使用抗生素以及是否同时使用乳果糖、利福昔明或PPI，粪便移植后β-内酰胺酶和万古霉素耐药基因减少。 抗生素耐药性导致肝硬化预后不良。粪便微生物群移植（FMT）与非肝硬化患者抗生素耐药基因（ARG）负荷的减少有关;然而，对肝硬化的影响尚不清楚。我们的目的是研究胶囊和灌肠剂FMT对粪便样本中ARG丰度的影响，这些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中进行的，这些患者接受利福昔明、乳果糖和质子泵抑制剂。使用宏基因组学鉴定ARG，并将其映射到综合抗生素耐药性数据库。研究组内/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周采集粪便。抗生素+灌肠剂FMT包括术前抗生素，随后FMT灌肠剂与标准治疗（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例患者。没有与FMT相关的安全性/感染信号。在胶囊试验中，与基线相比，FMT后β-内酰胺酶（OXY/LEN）表达降低。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;后者与认知改善相关。在接受安慰剂治疗的患者中未观察到变化。在抗生素+灌肠试验中，第7天与基线相比，万古霉素和β-内酰胺酶ARG增加，第15天下降。然而，喹诺酮耐药性在第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）大大降低，并在第15天继续降低（cepA β-内酰胺酶，VanW）。SOC组内未观察到变化。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基线和非FMT组相比，FMT后ARG丰度大幅降低。
Fecal transplant is associated with reduction in the expression of antibiotic‐resistance genes in patients with decompensated cirrhosis. Genes focused on beta‐lactamase and vancomycin resistance reduced after fecal transplant regardless of pre‐procedure antibiotics and concurrent use of lactulose, rifaximin or PPIs. 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.
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DOI：
10.1093/cid/cix270
发表时间：
2017-07-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Gorrie CL;Mirceta M;Wick RR;Edwards DJ;Thomson NR;Strugnell RA;Pratt NF;Garlick JS;Watson KM;Pilcher DV;McGloughlin SA;Spelman DW;Jenney AWJ;Holt KE
通讯作者：
Holt KE
影响因子：
13.5
作者：
Bajaj, Jasmohan S.;Kakiyama, Genta;Gillevet, Patrick M.
通讯作者：
Gillevet, Patrick M.
粪便微生物移植减少了艰难梭菌感染的患者中抗生素耐药基因。
DOI：
10.1093/cid/ciw185
发表时间：
2016-06-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Millan B;Park H;Hotte N;Mathieu O;Burguiere P;Tompkins TA;Kao D;Madsen KL
通讯作者：
Madsen KL
影响因子：
9.8
作者：
Bajaj, Jasmohan S.;O'Leary, Jacqueline G.;Reddy, K. Rajender
通讯作者：
Reddy, K. Rajender
影响因子：
5.2
作者：
Olsen, JE;Christensen, H;Aarestrup, FM
通讯作者：
Aarestrup, FM