Wang Yiwen, Wang Yue, Han Wenjie, Han Mengzhen, Liu Xiaolin, Dai Jianying, Dong Yuesheng, Sun Tao, Xu Junnan
Department of Breast Medicine 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China.
Department of Pharmacology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China.
Front Cell Infect Microbiol. 2024 Sep 17;14:1397466. doi: 10.3389/fcimb.2024.1397466. eCollection 2024.
The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets.
We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions.
The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non- commensals, which are crucial in both -negative and -positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712).
This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified and as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of and as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.
胃肠道微生物群失调与胃癌（GC）之间的关系已得到广泛研究。然而，不同研究中GC患者的微生物群变化差异很大，且在多人群中仍缺乏可重复的早期GC诊断生物标志物。因此，本研究旨在通过对多个已发表和公开数据集的荟萃分析，来描述参与胃癌发生的胃肠道微生物群落特征。
我们分析了来自11项独立研究的1642份胃活检样本和394份粪便样本的16S rRNA测序数据。使用VSEARCH、QIIME以及vegan、phyloseq、cooccur和random forest等R包进行数据处理和分析。采用PICRUSt软件预测功能。
α多样性结果表明，与非癌症患者相比，癌症患者肿瘤内微生物群存在显著差异，而粪便微生物群未观察到显著差异。网络分析表明，与健康个体相比，与GC富集菌的正相关性增加，与GC耗竭菌的正相关性降低。功能分析表明，与碳水化合物代谢相关的途径在GC中显著富集，而不饱和脂肪酸的生物合成减少。此外，我们研究了在阴性和阳性GC中均起关键作用的非共生菌。使用从LEfSe分析中确定的与GC相关的特定分类群构建的随机森林模型显示，单独的乳酸杆菌和链球菌组合能够有效区分粪便样本中的GC患者和健康个体（曲线下面积（AUC）=0.7949）。这一发现也在一个独立队列中得到验证（AUC = 0.7712）。
本研究从双重微生态角度研究了GC患者的肿瘤内和粪便微生物群，鉴定出[具体细菌名称未给出]作为肿瘤内和肠道特异性共差异细菌。此外，它证实了[具体细菌名称未给出]组合作为多人群GC特异性微生物标志物的有效性，这可能有助于GC的早期非侵入性诊断。
