Department of Neurosurgery, The Affiliated Hospital of Yangzhou University, Yangzhou, China.
Department of Neurosurgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng, China.
Front Cell Infect Microbiol. 2024 Jan 18;13:1211855. doi: 10.3389/fcimb.2023.1211855. eCollection 2023.
The elevated mortality rate associated with non-small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward exploring the association between gut microbiota and various malignant tumors. We herein investigated the associations between the intestinal microbiome and its metabolites, particularly short-chain fatty acids (SCFAs), in patients with NSCLC at different stages, including early and brain metastasis (BM) stages. The findings aim to offer a fresh perspective on the diagnosis and management of NSCLC.
Fecal samples were collected from 115 participants, comprising healthy controls (n = 35) and patients with treatment-naive NSCLC at the early stage (ELC, n = 40) and the BM stage (n = 40). Characterization of the intestinal microbiome and fecal SCFA levels was performed using 16S rRNA gene sequencing and gas chromatography.
The microbial diversity in patients with NSCLC was found to be less abundant and uniform, particularly in the BM stage. Significant alterations in the community structure of the gut microbiota were observed in patients with NSCLC, with an increase in pathogens in Fusobacteria and Proteobacteria and a decrease in SCFA-producing bacteria in Firmicutes and Actinobacteria, particularly in the BM stage. Meanwhile, microbial communities displayed intricate associations in patients with NSCLC. A biomarker panel (, , , , , and ) successfully distinguished patients in the ELC and BM stages from healthy controls (area under the curve: 0.884). The overall concentration of fecal SCFAs was significantly lower in patients with BM compared to patients with ELC and healthy controls. Subgroup analysis of acetate and butyrate yielded similar results. Moreover, multiple disrupted pathways in the NSCLC group were identified using the Kyoto Encyclopedia of Genes and Genomes annotation, including lipid metabolism and genetic information processing, specifically in the BM stage.
Compared with healthy controls, distinct host-microbe interactions were evident in different phases of patients with NSCLC. Furthermore, specific forms of the gut microbiome and SCFAs may serve as valuable biomarkers and therapeutic targets in the diagnosis and treatment of NSCLC.
非小细胞肺癌（NSCLC）相关的高死亡率是一个既定的全球关注点。人们对肠道微生物群与各种恶性肿瘤之间的关联给予了相当多的关注。本研究旨在调查不同阶段 NSCLC 患者（包括早期和脑转移（BM）阶段）的肠道微生物群及其代谢物，特别是短链脂肪酸（SCFA）之间的关联。这些发现旨在为 NSCLC 的诊断和治疗提供新的视角。
收集了 115 名参与者的粪便样本，包括健康对照组（n=35）和未经治疗的早期 NSCLC 患者（ELC，n=40）和 BM 阶段患者（n=40）。使用 16S rRNA 基因测序和气相色谱法对肠道微生物群和粪便 SCFA 水平进行了表征。
发现 NSCLC 患者的微生物多样性较少且均匀，特别是在 BM 阶段。在 NSCLC 患者中观察到肠道微生物群群落结构的显著改变，其中梭菌和变形菌的病原体增加，厚壁菌门和放线菌门的 SCFA 产生菌减少，特别是在 BM 阶段。同时，在 NSCLC 患者中微生物群落显示出复杂的关联。一个生物标志物面板（，，，，，和）成功地区分了 ELC 和 BM 阶段的患者与健康对照组（曲线下面积：0.884）。与 ELC 患者和健康对照组相比，BM 患者的粪便 SCFA 总浓度显著降低。乙酸盐和丁酸盐的亚组分析也得出了类似的结果。此外，通过京都基因与基因组百科全书注释鉴定了 NSCLC 组中多个被破坏的途径，包括脂质代谢和遗传信息处理，特别是在 BM 阶段。
与健康对照组相比，NSCLC 不同阶段的患者存在明显的宿主-微生物相互作用。此外，特定形式的肠道微生物群和 SCFA 可能作为 NSCLC 诊断和治疗有价值的生物标志物和治疗靶点。
