摘要

预防多药耐药微生物（MDRO）感染的策略很少，但自体粪便微生物群移植（autoFMT）可能会限制胃肠道MDRO扩张。 AutoFMT涉及在健康状态下将一个人的粪便储存起来，以便以后用于在扰动后恢复肠道微生物群。该初步研究评估了autoFMT对阿莫西林 - 克拉维酸（Amox-Clav）暴露后胃肠道微生物组分类组成，抗性基因含量和代谢能力的影响。招募了10名健康参与者。所有人都收到了5天的Amox-Clav。一半被随机分配到autoFMT，来自粪便前抗菌暴露，灌肠，一半来源于盐水灌肠。参与者在Amox-Clav和灌肠前后以及90天的随访期间提交了粪便样本。 Shotgun宏基因组测序揭示了分类组成，抗性基因含量和代谢能力。 Amox-Clav显着改变所有参与者的肠道分类组成（n = 10，P <0.01）;然而，只有三名参与者在接触后在门阶段表现出重大变化。在整个队列中，β-内酰胺酶基因在Amox-Clav后富集（P <0.05），并且预测的代谢能力显着改变（P <0.01）。在autoFMT或盐水灌肠后7天，物种组成，代谢能力和β-内酰胺酶丰度恢复到抗微生物前暴露状态（P> 0.05，与登记相比）。即使在没有实质性分类破坏的参与者中，抗微生物暴露后微生物代谢能力也会发生变化，可能为病原体定植创造开放的利基。我们的研究结果表明，代谢潜力是完全评估抗微生物对微生物组影响的重要考虑因素。 AutoFMT耐受性良好，可能有助于系统发育恢复。 （该研究已在ClinicalTrials.gov注册，标识号为NCT02046525。）重要性病原生物中多药耐药性的传播威胁到抗菌治疗方案的功效。人体肠道充当许多抗药性生物及其抗性基因的储库，并且通过抗微生物暴露扰乱肠道微生物组可以打开耐药病原体的代谢生态位。一旦在肠道中建立，即使在抗菌剂暴露停止后，抗微生物抗性细菌也会持续存在。预防多药耐药微生物（MDRO）感染的策略很少，但自体粪便微生物群移植（autoFMT）可能会限制胃肠道MDRO扩张。 AutoFMT涉及在健康状态下将一个人的粪便储存起来，以便以后用于在扰动后恢复肠道微生物群。该初步研究评估了阿莫西林 - 克拉维酸（Amox-Clav）暴露和autoFMT对胃肠道微生物组分类组成，抗性基因含量和代谢能力的影响。重要的是，我们发现即使在总体系统发育保持不变且autoFMT安全且耐受良好的情况下，代谢能力也会受到干扰。

Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P < 0.01); however, only three participants exhibited major changes at the phylum level following exposure. In the cohort as a whole, beta-lactamase genes were enriched following Amox-Clav (P < 0.05), and predicted metabolic capacity was significantly altered (P < 0.01). Species composition, metabolic capacity, and beta-lactamase abundance returned to pre-antimicrobial exposure state 7 days after either autoFMT or saline enema (P > 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.)IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.

https://www.ncbi.nlm.nih.gov/pubmed/30463925