摘要
      2019年冠状病毒（新冠肺炎）患者肠道微生物群失调的情况很清楚，但抗生素耐药基因（ARGs）库（称为耐药组）的动态尚不清楚。在这里，我们对142名新冠肺炎患者进行了纵向粪便宏基因组分析，描述了从诊断到病毒清除后6个月的耐药组动态，并报告了抗生素或益生菌对ARG库的影响。基线时，与非新冠肺炎对照组相比，新冠肺炎抗菌素阳性患者的数量和类型增加，ARG的患病率更高。耐药组的扩展主要由四环素、万古霉素和耐多药基因驱动，并在严重急性呼吸系统综合征冠状病毒2型清除后持续至少6个月。耐药组扩大的患者克雷伯菌和急性新冠肺炎综合征的发病率增加。抗生素治疗进一步增加了ARG的丰度，而口服益生菌（合生菌配方，SIM01）显著减少了急性感染和恢复期新冠肺炎患者肠道微生物群中ARG的蓄积。总之，这些发现对新冠肺炎患者ARG蓄积的动态以及微生物群导向治疗在减轻累积ARG负担方面的潜在作用提供了新的见解。
ABSTRACT
Dysbiosis of gut microbiota is well-described in patients with coronavirus 2019 (COVID-19), but the dynamics of antimicrobial resistance genes (ARGs) reservoir, known as resistome, is less known. Here, we performed longitudinal fecal metagenomic profiling of 142 patients with COVID-19, characterized the dynamics of resistome from diagnosis to 6 months after viral clearance, and reported the impact of antibiotics or probiotics on the ARGs reservoir. Antibiotic-naive patients with COVID-19 showed increased abundance and types, and higher prevalence of ARGs compared with non-COVID-19 controls at baseline. Expansion in resistome was mainly driven by tetracycline, vancomycin, and multidrug-resistant genes and persisted for at least 6 months after clearance of SARS-CoV-2. Patients with expanded resistome exhibited increased prevalence of Klebsiella sp. and post-acute COVID-19 syndrome. Antibiotic treatment resulted in further increased abundance of ARGs whilst oral probiotics (synbiotic formula, SIM01) significantly reduced the ARGs reservoir in the gut microbiota of COVID-19 patients during the acute infection and recovery phase. Collectively, these findings shed new insights on the dynamic of ARGs reservoir in COVID-19 patients and the potential role of microbiota-directed therapies in reducing the burden of accumulated ARGs.

https://www.tandfonline.com/doi/full/10.1080/19490976.2022.2128603