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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02803-3

摘要内容如下：

针对肠道微生物组的多项临床试验正在进行，以优化免疫检查点阻断（ICB）的治疗结果。为了提高这些干预措施的成功率，迫切需要了解ICB期间肠道微生物组的变化。通过对175例接受ICB治疗的晚期黑色素瘤患者进行纵向微生物组分析，我们发现，在达到12个月或更长时间（PFS≥12）的无进展生存期（PFS）的患者与PFS短于12个月（PFS<12）的患者中，几种微生物物种水平的基因组库（SGBs）和途径表现出与基线不同的模式。在99个可以区分这两组的SGBs中，20个仅在基线时有差异，而42个仅在治疗开始后有差异。我们分别确定了5个和4个在PFS≥12个月和<12个月的患者中具有持续较高丰度的SGB。构建这些SGB的对数比率，我们发现与总生存率相关。最后，我们发现在不同的临床背景下，包括ICB方案的类型、免疫相关不良事件的发生和合并用药，微生物动力学也有所不同。深入了解与宿主因素和治疗方案相关的肠道微生物组的纵向动力学，对于指导旨在增强ICB疗效的合理微生物组靶向治疗至关重要。

英文原文如下：

Abstracts

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.

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