Table_4_The Gastric Microbiome Is Perturbed in Advanced Gastric Adenocarcinoma Identified Through Shotgun Metagenomics.xlsx

Objective: Dysbiosis of gastric microbiota such as Helicobacter pylori plays a significant role in pathogenesis and progression of gastric cancer. Our aim was to evaluate the composition and functional effects of gastric microbiota in superficial gastritis (SG) and advanced gastric adenocarcinoma (GC).Methods: We carried out shotgun metagenomic sequencing on gastric wash samples from 6 patients with GC and 5 patients with SG. The taxonomic composition was profiled using MetaPhlAn2 and functional gene pathway was profiled using HUMAnN2. Differences in microbial composition and pathways between the two patient groups were assessed via LEfSe.Results: The gastric microbiota in GC patients was characterized by reduced species richness, enrichment of 13 bacterial taxa and depletion of 31 taxa (q < 0.05). The most representative taxa which were abundant in GC corresponded to the commensals or opportunistic pathogens that usually colonize the oral cavity, including genera Neisseria, Alloprevotella, and Aggregatibacter, species Streptococcus_mitis_oralis_pneumoniae and strain Porphyromonas_endodontalis.t_GCF_000174815. Each of the three GC-associated genera could separate GC from SG completely. In particular, Sphingobium yanoikuyae, a bacterium capable of degrading carcinogenic compounds, was depleted in GC. Functionally, pathways associated with the biosynthesis of lipopolysaccharide (LPS) and L-arginine were enriched in GC, whereas pathways involved in the fermentation of short chain fatty acids (SCFAs) and branched amino acid metabolism were more abundant in SG.Conclusions: Our results present new alterations in the gastric microbiome in patients with GC from a whole-genome perspective, suggesting that microbiome composition and function can be used for prognosis and diagnosis of GC.

研究目标：幽门螺杆菌等胃微生物群失调在胃癌的发病机制和进展中发挥着重要作用。本研究的目的是评估胃微生物群在表浅胃炎（SG）和进展期胃腺癌（GC）中的组成和功能效应。研究方法：我们对6名GC患者和5名SG患者的胃洗脱样本进行了宏基因组测序。利用MetaPhlAn2对分类组成进行剖析，利用HUMAnN2对功能基因通路进行剖析。通过LEfSe方法评估两组患者间微生物组成和通路的差异。研究结果：GC患者的胃微生物群特征为物种丰富度降低，13种细菌类群富集，31种类群减少（q < 0.05）。在GC中富集的代表性类群，包括通常定植于口腔的共生体或机会性病原体，如奈瑟菌属、拟普雷沃菌属和聚集性细菌属，以及物种如口腔链球菌、肺炎链球菌和牙龈卟啉单胞菌菌株Porphyromonas_endodontalis.t_GCF_000174815。这三个与GC相关的属均能完全区分GC与SG。特别是，能够降解致癌物质的细菌Sphingobium yanoikuyae在GC中减少。在功能上，与脂多糖（LPS）和L-精氨酸生物合成相关的通路在GC中富集，而涉及短链脂肪酸（SCFAs）发酵和分支氨基酸代谢的通路在SG中更为丰富。研究结论：我们的结果从全基因组视角呈现了GC患者胃微生物群的新变化，表明微生物群的组成和功能可用于GC的预后和诊断。