宏基因组关联研究揭示了肠道微生物组与局部晚期和晚期肺癌化疗结果相关的生物标志物。

BACKGROUND: The gut microbiome is important in the development and immunotherapy efficacy of lung cancer. However, the relationship between the intestinal flora and chemotherapy outcomes remains unclear and was investigated in this study. METHODS: We analyzed baseline stool samples from patients with locally advanced and advanced lung cancer before chemotherapy treatment, through metagenomics of the gut microbiota. The composition, diversity, function, and metabolic pathway analysis were compared among patients with different clinical outcomes. RESULTS: From 64 patients, 33 responded to treatment (responders) and 31 did not (nonresponders). Streptococcus mutans and Enterococcus casseliflavus were enriched in responders (P < 0.05), while 11 bacteria including Leuconostoc lactis and Eubacterium siraeum were enriched in nonresponders (P < 0.05) by variance analysis. Responders were associated with significantly higher Acidobacteria and Granulicella, while Streptococcus oligofermentans, Megasphaera micronuciformis, and Eubacterium siraeum were more abundant in nonresponders by Lefse analysis. Streptococcus mutans and Enterococcus casseliflavus were further identified as bacterial markers relevant to responders using unsupervised clustering, and Leuconostoc lactis and Eubacterium siraeum were related to nonresponders. The L-glutamate degradation VIII pathway was enriched in responders (P = 0.014), and the C4 photosynthetic carbon assimilation cycle, reductive TCA cycle I, and hexitol fermentation to lactate, formate, ethanol, and acetate were enriched in nonresponders (P < 0.05). Additionally, significant associations of bacterial species with clinical phenotypes were observed by Spearman correlation analysis. CONCLUSIONS: The specific gut microbiome of patients with lung cancer might be connected to the clinical outcomes of chemotherapy. KEY POINTS: Significant findings of the study Lung cancer patients with different gut microbiome compositions and microbiome metabolic pathways have different responses to chemotherapy. Microbiome species are also associated with different lung cancer clinical phenotypes. What this study adds We have identified specific gut microbiome species that can be used as relevant biomarkers for chemotherapy outcomes. This can potentially be used to guide clinical treatment decisions.

背景：肠道微生物群在肺癌的发生和免疫治疗效果中具有重要作用。然而，肠道菌群与化疗结果之间的关系尚不清楚，本研究对此进行了探讨。

方法：我们通过肠道微生物组学分析了 64 例局部晚期和晚期肺癌患者化疗前的基线粪便样本。比较了不同临床结局患者的菌群组成、多样性、功能和代谢途径分析。

结果：64 例患者中，33 例治疗有效（应答者），31 例无效（无应答者）。应答者中变形链球菌和粪肠球菌丰度较高（P<0.05），而无应答者中乳杆菌和真杆菌等 11 种细菌丰度较高（P<0.05），通过方差分析得出。应答者与厚壁菌门和 Granulicella 显著相关，而寡养单胞菌、微小消化链球菌和真杆菌在无应答者中更为丰富，通过 Lefse 分析得出。通过无监督聚类分析，进一步确定变形链球菌和粪肠球菌为与应答者相关的细菌标志物，而乳杆菌和真杆菌与无应答者相关。应答者中 L-谷氨酸降解 VIII 途径富集（P=0.014），而无应答者中 C4 光合作用碳同化循环、还原性三羧酸循环 I、己糖发酵为乳酸、甲酸、乙醇和乙酸等途径富集（P<0.05）。此外，通过 Spearman 相关性分析还观察到细菌种类与临床表型之间存在显著关联。

结论：肺癌患者的特定肠道微生物群可能与化疗的临床结局有关。

关键点：本研究的重要发现：不同肠道微生物群组成和微生物群代谢途径的肺癌患者对化疗的反应不同。微生物群物种也与不同的肺癌临床表型相关。本研究的意义：我们已经确定了可作为化疗结果相关生物标志物的特定肠道微生物群物种。这可能有助于指导临床治疗决策。