Gut Microbiome Signatures are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia

The majority of studies providing insights on the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. In this investigation we examined microbiome characteristics from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 acute myeloid leukemia patients. We aimed to assess the predictive capacity of the gastrointestinal microbiome and its relationship to clinical outcomes, with a specific focus on infection. At the start of IC, higher Shannon diversity (HR, 0.36; P=0.005) and higher relative abundance of Porphyromonadaceae (HR, 0.36; P=0.005) were associated with increased probability of remaining infection free during neutropenia. We determined baseline Shannon diversity values <2 had the best sensitivity, positive, and negative predictive value for infectious complications during neutropenia. Longitudinal analyses of microbiome trajectories from baseline until neutrophil recovery found greater decreases in stool Shannon diversity among subjects who developed an infection in the 90 days post neutrophil recovery (P = 0.003). Additionally, carbapenem receipt for >72hrs resulted in significantly lower α-diversity at neutrophil recovery (P=0.001) and was associated with increased incidence of infection in the 90 days following neutrophil recovery (HR, 4.55; P=0.002). Similarly, days on treatment antibiotics during IC was inversely correlated with Shannon diversity at the end of sampling (r=-0.40, P<0.001) and the cumulative incidence of infections in the 90 days post neutrophil recovery (HR, 1.04; P=0.002). Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that antibiotic administration during IC may influence infectious complications of hematologic malignancy patients.

目前针对微生物组对血液系统恶性肿瘤患者健康影响的相关研究，大多聚焦于移植场景。本研究对97例急性髓系白血病（acute myeloid leukemia）患者在诱导化疗（induction chemotherapy, IC）后，从基线至中性粒细胞恢复阶段的微生物组特征进行了检测分析，旨在评估胃肠道微生物组的预测效能及其与临床结局的关联，重点关注感染事件。在诱导化疗起始阶段，较高的香农多样性指数（Shannon diversity）（风险比hazard ratio, HR=0.36；P=0.005）以及较高的卟啉单胞菌科（Porphyromonadaceae）相对丰度（HR=0.36；P=0.005），与中性粒细胞减少症（neutropenia）期间维持无感染状态的概率升高显著相关。我们发现，基线72小时内的香农多样性指数水平，与中性粒细胞恢复阶段较低的α多样性（α-diversity）显著相关（P=0.001），同时与中性粒细胞恢复后90天内的感染发生率升高相关（HR=4.55；P=0.002）。同样，诱导化疗期间抗菌药物使用时长，与采样结束时的香农多样性指数呈负相关（相关系数r=-0.40，P<0.001），且与中性粒细胞恢复后90天内的累积感染发生率相关（HR=1.04；P=0.002）。本研究结果表明，肠道微生物组评估可辅助感染风险分层，且诱导化疗期间的抗菌药物使用可能会影响血液系统恶性肿瘤患者的感染并发症发生情况。