N/A, ProgenaBiome LLC, Ventura, California, USA
Division of Gastroenterology, Alta Bates Summit Medical Center, Berkeley, California, USA.
BMJ Open Gastroenterol. 2022 Apr;9(1). doi: 10.1136/bmjgast-2022-000871.
The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.
Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.
Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of (p<0.0001), (p=0.0077) and (p=0.0327), while having increased (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.
We hypothesise that low bacterial diversity and depletion of genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention.
NCT04031469 (PCR-) and 04359836 (PCR+).
本研究旨在比较症状从无症状到重度的 SARS-CoV-2 PCR 阳性患者与 PCR 阴性暴露对照者的肠道微生物组多样性和组成。
采用横断面设计,我们对粪便样本进行了 shotgun 下一代测序,以评估 2020 年 3 月至 2021 年 10 月期间因 COVID-19 前往 Ventura 临床试验接受治疗的 SARS-CoV-2 PCR 确诊感染患者和 SARS-CoV-2 PCR 阴性暴露对照者的肠道微生物组组成和多样性。根据美国国立卫生研究院的标准,将患者分为无症状或有轻度、中度或重度症状。暴露对照者是指与 SARS-CoV-2 感染患者或其样本有长时间或反复密切接触的个体,例如患者的家庭成员或一线医护人员。在所有分类水平上比较了患者和暴露对照者的微生物组多样性和组成。
与对照者(n=20)相比,症状严重的 SARS-CoV-2 感染患者(n=28)的细菌多样性明显较低(Shannon 指数,p=0.0499;Simpson 指数,p=0.0581),总体阳性患者的相对丰度较低(p<0.0001),(p=0.0077)和(p=0.0327),而(p=0.0075)增加。有趣的是,疾病严重程度与相同细菌的丰度之间存在反比关系。
我们假设,细菌多样性降低和属的耗竭无论是在感染前还是感染后,都会导致免疫原性功能降低,从而使 SARS-CoV-2 感染出现症状。这种特定的肠道微生态失调模式可能是 SARS-CoV-2 感染症状严重程度的易感标志物,并且可能适合于感染前、感染中和感染后的干预。
NCT04031469(PCR-)和 04359836(PCR+)。