Pediatric Gastroenterology, Hepatology and Nutrition Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 52620000, Tel Hashomer, Ramat-Gan, Israel.
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Sci Rep. 2023 Feb 3;13(1):2007. doi: 10.1038/s41598-023-29136-4.
We aimed to determine microbial signature linked with lung cancer (LC) diagnosis and to define taxa linked with durable clinical benefit (DCB) of advanced LC patients. Stool samples for microbial 16S amplicon sequencing and clinical data were collected from 75 LC patients (50 of which were treated with checkpoint inhibitors) and 31 matched healthy volunteers. We compared LC to healthy controls and patients with DCB to those without. LC patients had lower α-diversity and higher between-subject diversity. Random Forests model to differentiate LC cases from controls ROC-AUC was 0.74. Clostridiales, Lachnospiraceae, and Faecalibacterium prausnitzii taxa abundance was decreased in LC compared to controls. High Akkermansia muciniphila correlated with DCB (HR 4.26, 95% CI 1.98-9.16), not only for the immunotherapy-treated patients. In addition, high Alistipes onderdonkii (HR 3.08, 95% CI 1.34-7.06) and high Ruminococcus (HR 7.76, 95% CI 3.23-18.65) correlated with DCB.Our results support the importance of gut microbiome in LC. We have validated the apparent predictive value of Akkermansia muciniphila, and highlighted Alistipes onderdonkii and Ruminococcus taxa correlation with DCB. Upon additional validations those can be used as biomarkers or as targets for future therapeutic interventions.
我们旨在确定与肺癌（LC）诊断相关的微生物特征，并确定与晚期 LC 患者持久临床获益（DCB）相关的分类群。从 75 名 LC 患者（其中 50 名接受检查点抑制剂治疗）和 31 名匹配的健康志愿者中收集了用于微生物 16S 扩增子测序和临床数据的粪便样本。我们将 LC 与健康对照组进行了比较，并将具有 DCB 的患者与无 DCB 的患者进行了比较。LC 患者的 α-多样性较低，个体间差异较大。用于区分 LC 病例与对照的随机森林模型 ROC-AUC 为 0.74。与对照组相比，LC 患者中的 Clostridiales、Lachnospiraceae 和 Faecalibacterium prausnitzii 分类群丰度降低。高 Akkermansia muciniphila 与 DCB 相关（HR 4.26，95%CI 1.98-9.16），不仅在免疫治疗组患者中如此。此外，高 Alistipes onderdonkii（HR 3.08，95%CI 1.34-7.06）和高 Ruminococcus（HR 7.76，95%CI 3.23-18.65）与 DCB 相关。我们的结果支持肠道微生物组在 LC 中的重要性。我们已经验证了 Akkermansia muciniphila 的明显预测价值，并强调了 Alistipes onderdonkii 和 Ruminococcus 分类群与 DCB 的相关性。在进一步验证后，这些可以用作生物标志物或作为未来治疗干预的目标。
