Rationale Inflammation is present in several conditions associated with risk of venous thromboembolism. The gut microbiome might be a source of systemic inflammation and activation of coagulation, by translocation of lipopolysaccharides from gram-negative bacteria to the systemic circulation.

Objective To investigate whether a vancomycin-induced shift of the gut microbiome in a gram-negative direction influences systemic inflammation and plasma factor (F) VIII procoagulant activity (FVIII:C).

Methods and Results We performed a randomized controlled trial including 43 healthy volunteers aged 19 to 37 years. Twenty-one were randomized to 7 days of oral vancomycin intake and 22 served as controls. Feces and blood were sampled at baseline, the day after the end of intervention, and 3 weeks after intervention. Gut microbiome composition was assessed by amplicon sequencing. FVIII:C was measured using an activated partial thromboplastin time-based assay, cytokines were measured using multiplex technology, complement activation was measured using the enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (CRP) was measured by an immunoturbidimetric assay. Vancomycin intake reduced gut microbiome diversity and increased the abundance of gram-negative bacteria. Change in FVIII:C in the intervention group was +4 IU/dL versus −6 IU/dL (p = 0.01) in the control group. A similar change was observed for log-transformed CRP (+0.21 mg/dL vs. −0.25 mg/dL, p = 0.04). The cytokines and complement activation markers remained similar in the two groups.

Conclusion The found slight increases in FVIII:C and CRP levels might support the hypothesis that a vancomycin-induced gram-negative shift in the gut microbiome could induce increased systemic inflammation and thereby a procoagulant state.

基本原理 炎症存在于与静脉血栓栓塞风险相关的几种情况中。通过脂多糖从革兰氏阴性菌转移到全身循环，肠道微生物组可能是全身炎症和凝血激活的来源。

目的 研究万古霉素诱导的肠道微生物群向革兰氏阴性方向的转变是否会影响全身炎症和血浆因子 (F) VIII 促凝活性 (FVIII:C)。

方法和结果 我们进行了一项随机对照试验，包括 43 名 19 至 37 岁的健康志愿者。21 人被随机分配至口服万古霉素 7 天，其中 22 人作为对照。在基线、干预结束后的第二天和干预后 3 周采集粪便和血液样本。通过扩增子测序评估肠道微生物组组成。FVIII:C 使用基于时间的活化部分促凝血酶原激酶测定法测量，细胞因子使用多重技术测量，补体激活使用酶联免疫吸附测定法测量，高敏 C 反应蛋白 (CRP) 使用免疫比浊法测量化验。万古霉素的摄入降低了肠道微生物组的多样性并增加了革兰氏阴性菌的丰度。干预组中 FVIII:C 的变化分别为 +4 IU/dL 和 -6 IU/dL（p  = 0.01) 在对照组中。对数转换的 CRP 也观察到了类似的变化（+0.21 mg/dL 对 -0.25 mg/dL，p  = 0.04）。两组的细胞因子和补体激活标志物保持相似。

结论 所发现的 FVIII:C 和 CRP 水平的轻微升高可能支持万古霉素诱导的肠道微生物组革兰氏阴性转变可诱导全身炎症增加从而导致促凝状态的假设。